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1. Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma

Author: Linder, A., Westbom-Fremer, S., Mateoiu, C., Olsson Widjaja, A., Österlund, T., Veerla, S., Ståhlberg, A., Ulfenborg, Benjamin, Hedenfalk, I., Sundfeldt, K., Linder, A., Westbom-Fremer, S., Mateoiu, C., Olsson Widjaja, A., Österlund, T., Veerla, S., Ståhlberg, A., Ulfenborg, Benjamin, Hedenfalk, I., and Sundfeldt, K.
Abstract: STUDY QUESTION: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations), CC BY-NC 4.0 DeedPublished: 09 March 2024Correspondence address: Karin Sundfeldt, Department of Obstetrics and Gynecology, Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academyat University of Gothenburg, SE-405 30 Gothenburg, Sweden. E-mail: karin.sundfeldt@gu.se (K.S.) https://orcid.org/0000-0002-7135-3132;Division of Oncology,Department of Clinical Sciences Lund, Lund University, SE-223 81 Lund, Sweden. E-mail: ingrid.hedenfalk@med.lu.se (I.H.) https://orcid.org/0000-0002-6840-3The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE—a strategic research area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad’s Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden’s Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021- 01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.).
Published: 2024
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2. Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma.

Author: Linder, A, Westbom-Fremer, S, Mateoiu, C, Widjaja, A Olsson, Österlund, T, Veerla, S, Ståhlberg, A, Ulfenborg, B, Hedenfalk, I, and Sundfeldt, K
Subjects: RENAL cell carcinoma, ENDOMETRIOSIS, SOMATIC mutation, DNA repair, GENETIC profile, HEREDITARY nonpolyposis colorectal cancer
Abstract: STUDY QUESTION Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998–2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively. MAIN RESULTS AND THE ROLE OF CHANCE The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7–30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P < 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases. LARGE SCALE DATA Datasets are available in the supplementary tables. LIMITATIONS, REASONS FOR CAUTION Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association. WIDER IMPLICATIONS OF THE FINDINGS The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events. STUDY FUNDING/COMPETING INTEREST(S) The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE—A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. [ABSTRACT FROM AUTHOR]
Published: 2024
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3. Concurrent RB1 loss and BRCA-deficiency predicts enhanced immunological response and long-term survival in tubo-ovarian high-grade serous carcinoma.

Author: Saner, FAM, Takahashi, K, Budden, T, Pandey, A, Ariyaratne, D, Zwimpfer, TA, Meagher, NS, Fereday, S, Twomey, L, Pishas, KI, Hoang, T, Bolithon, A, Traficante, N, Alsop, K, Christie, EL, Kang, E-Y, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Alsop, J, Beckmann, MW, Boros, J, Brand, AH, Brooks-Wilson, A, Carney, ME, Coulson, P, Courtney-Brooks, M, Cushing-Haugen, KL, Cybulski, C, El-Bahrawy, MA, Elishaev, E, Erber, R, Gayther, SA, Gentry-Maharaj, A, Blake Gilks, C, Harnett, PR, Harris, HR, Hartmann, A, Hein, A, Hendley, J, AOCS Group, Hernandez, BY, Jakubowska, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Kluz, T, Koziak, JM, Kristjansdottir, B, Le, ND, Lener, M, Lester, J, Lubiński, J, Mateoiu, C, Orsulic, S, Ruebner, M, Schoemaker, MJ, Shah, M, Sharma, R, Sherman, ME, Shvetsov, YB, Singh, N, Rinda Soong, T, Steed, H, Sukumvanich, P, Talhouk, A, Taylor, SE, Vierkant, RA, Wang, C, Widschwendter, M, Wilkens, LR, Winham, SJ, Anglesio, MS, Berchuck, A, Brenton, JD, Campbell, I, Cook, LS, Doherty, JA, Fasching, PA, Fortner, RT, Goodman, MT, Gronwald, J, Huntsman, DG, Karlan, BY, Kelemen, LE, Menon, U, Modugno, F, Pharoah, PDP, Schildkraut, JM, Sundfeldt, K, Swerdlow, AJ, Goode, EL, DeFazio, A, Köbel, M, Ramus, SJ, Bowtell, DDL, Garsed, DW, Saner, FAM, Takahashi, K, Budden, T, Pandey, A, Ariyaratne, D, Zwimpfer, TA, Meagher, NS, Fereday, S, Twomey, L, Pishas, KI, Hoang, T, Bolithon, A, Traficante, N, Alsop, K, Christie, EL, Kang, E-Y, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Alsop, J, Beckmann, MW, Boros, J, Brand, AH, Brooks-Wilson, A, Carney, ME, Coulson, P, Courtney-Brooks, M, Cushing-Haugen, KL, Cybulski, C, El-Bahrawy, MA, Elishaev, E, Erber, R, Gayther, SA, Gentry-Maharaj, A, Blake Gilks, C, Harnett, PR, Harris, HR, Hartmann, A, Hein, A, Hendley, J, AOCS Group, Hernandez, BY, Jakubowska, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Kluz, T, Koziak, JM, Kristjansdottir, B, Le, ND, Lener, M, Lester, J, Lubiński, J, Mateoiu, C, Orsulic, S, Ruebner, M, Schoemaker, MJ, Shah, M, Sharma, R, Sherman, ME, Shvetsov, YB, Singh, N, Rinda Soong, T, Steed, H, Sukumvanich, P, Talhouk, A, Taylor, SE, Vierkant, RA, Wang, C, Widschwendter, M, Wilkens, LR, Winham, SJ, Anglesio, MS, Berchuck, A, Brenton, JD, Campbell, I, Cook, LS, Doherty, JA, Fasching, PA, Fortner, RT, Goodman, MT, Gronwald, J, Huntsman, DG, Karlan, BY, Kelemen, LE, Menon, U, Modugno, F, Pharoah, PDP, Schildkraut, JM, Sundfeldt, K, Swerdlow, AJ, Goode, EL, DeFazio, A, Köbel, M, Ramus, SJ, Bowtell, DDL, and Garsed, DW
Abstract: BACKGROUND: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which frequently co-occurs with alterations in homologous recombination DNA repair genes including BRCA1 and BRCA2 (BRCA). We examined whether tumour expression of RB1 was associated with survival across ovarian cancer histotypes (HGSC, endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous carcinoma (LGSC)), and how co-occurrence of germline BRCA pathogenic variants and RB1 loss influences long-term survival in a large series of HGSC. PATIENTS AND METHODS: RB1 protein expression patterns were classified by immunohistochemistry in epithelial ovarian carcinomas of 7436 patients from 20 studies participating in the Ovarian Tumor Tissue Analysis consortium and assessed for associations with overall survival (OS), accounting for patient age at diagnosis and FIGO stage. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to survival, tumour infiltrating CD8+ lymphocyte counts and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cell lines with and without BRCA1 mutations to model co-loss with treatment response. We also performed genomic analyses on 126 primary HGSC to explore the molecular characteristics of concurrent homologous recombination deficiency and RB1 loss. RESULTS: RB1 protein loss was most frequent in HGSC (16.4%) and was highly correlated with RB1 mRNA expression. RB1 loss was associated with longer OS in HGSC (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.66-0.83, P = 6.8 ×10-7), but with poorer prognosis in ENOC (HR 2.17, 95% CI 1.17-4.03, P = 0.0140). Germline BRCA mutations and RB1 loss co-occurred in HGSC (P < 0.0001). Patients with both RB1 loss and germline BRCA mutations had a superior OS (HR 0.38, 95% CI 0.25-0.58, P = 5.2 ×10-6) compared to patients with either alteration alone, and their median OS was three times longer than non-carr
Published: 2023

4. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Author: Kang, E-Y, Weir, A, Meagher, NS, Farrington, K, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Bolithon, A, Popovic, G, Leung, B, Tang, K, Lambie, N, Millstein, J, Alsop, J, Anglesio, MS, Ataseven, B, Barlow, E, Beckmann, MW, Berger, J, Bisinotto, C, Boesmueller, H, Boros, J, Brand, AH, Brooks-Wilson, A, Brucker, SY, Carney, ME, Casablanca, Y, Cazorla-Jimenez, A, Cohen, PA, Conrads, TP, Cook, LS, Coulson, P, Courtney-Brooks, M, Cramer, DW, Crowe, P, Cunningham, JM, Cybulski, C, Darcy, KM, El-Bahrawy, MA, Elishaev, E, Erber, R, Farrell, R, Fereday, S, Fischer, A, Garcia, MJ, Gayther, SA, Gentry-Maharaj, A, Gilks, CB, Grube, M, Harnett, PR, Harrington, SP, Harter, P, Hartmann, A, Hecht, JL, Heikaus, S, Hein, A, Heitz, F, Hendley, J, Hernandez, BY, Hernando Polo, S, Heublein, S, Hirasawa, A, Hogdall, E, Hogdall, CK, Horlings, HM, Huntsman, DG, Huzarski, T, Jewell, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Khabele, D, Kommoss, FKF, Kruitwagen, RFPM, Lambrechts, D, Le, ND, Lener, M, Lester, J, Leung, Y, Linder, A, Loverix, L, Lubinski, J, Madan, R, Maxwell, GL, Modugno, F, Neuhausen, SL, Olawaiye, A, Olbrecht, S, Orsulic, S, Palacios, J, Pearce, CL, Pike, MC, Quinn, CM, Mohan, GR, Rodriguez-Antona, C, Ruebner, M, Ryan, A, Salfinger, SG, Sasamoto, N, Schildkraut, JM, Schoemaker, MJ, Shah, M, Sharma, R, Shvetsov, YB, Singh, N, Sonke, GS, Steele, L, Stewart, CJR, Sundfeldt, K, Swerdlow, AJ, Talhouk, A, Tan, A, Taylor, SE, Terry, KL, Toloczko, A, Traficante, N, Van de Vijver, KK, van der Aa, MA, Van Gorp, T, Van Nieuwenhuysen, E, Van-Wagensveld, L, Vergote, I, Vierkant, RA, Wang, C, Wilkens, LR, Winham, SJ, Wu, AH, Benitez, J, Berchuck, A, Candido Dos Reis, FJ, DeFazio, A, Fasching, PA, Goode, EL, Goodman, MT, Gronwald, J, Karlan, BY, Kommoss, S, Menon, U, Sinn, H-P, Staebler, A, Brenton, JD, Bowtell, DD, Pharoah, PDP, Ramus, SJ, Kobel, M, Kang, E-Y, Weir, A, Meagher, NS, Farrington, K, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Bolithon, A, Popovic, G, Leung, B, Tang, K, Lambie, N, Millstein, J, Alsop, J, Anglesio, MS, Ataseven, B, Barlow, E, Beckmann, MW, Berger, J, Bisinotto, C, Boesmueller, H, Boros, J, Brand, AH, Brooks-Wilson, A, Brucker, SY, Carney, ME, Casablanca, Y, Cazorla-Jimenez, A, Cohen, PA, Conrads, TP, Cook, LS, Coulson, P, Courtney-Brooks, M, Cramer, DW, Crowe, P, Cunningham, JM, Cybulski, C, Darcy, KM, El-Bahrawy, MA, Elishaev, E, Erber, R, Farrell, R, Fereday, S, Fischer, A, Garcia, MJ, Gayther, SA, Gentry-Maharaj, A, Gilks, CB, Grube, M, Harnett, PR, Harrington, SP, Harter, P, Hartmann, A, Hecht, JL, Heikaus, S, Hein, A, Heitz, F, Hendley, J, Hernandez, BY, Hernando Polo, S, Heublein, S, Hirasawa, A, Hogdall, E, Hogdall, CK, Horlings, HM, Huntsman, DG, Huzarski, T, Jewell, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Khabele, D, Kommoss, FKF, Kruitwagen, RFPM, Lambrechts, D, Le, ND, Lener, M, Lester, J, Leung, Y, Linder, A, Loverix, L, Lubinski, J, Madan, R, Maxwell, GL, Modugno, F, Neuhausen, SL, Olawaiye, A, Olbrecht, S, Orsulic, S, Palacios, J, Pearce, CL, Pike, MC, Quinn, CM, Mohan, GR, Rodriguez-Antona, C, Ruebner, M, Ryan, A, Salfinger, SG, Sasamoto, N, Schildkraut, JM, Schoemaker, MJ, Shah, M, Sharma, R, Shvetsov, YB, Singh, N, Sonke, GS, Steele, L, Stewart, CJR, Sundfeldt, K, Swerdlow, AJ, Talhouk, A, Tan, A, Taylor, SE, Terry, KL, Toloczko, A, Traficante, N, Van de Vijver, KK, van der Aa, MA, Van Gorp, T, Van Nieuwenhuysen, E, Van-Wagensveld, L, Vergote, I, Vierkant, RA, Wang, C, Wilkens, LR, Winham, SJ, Wu, AH, Benitez, J, Berchuck, A, Candido Dos Reis, FJ, DeFazio, A, Fasching, PA, Goode, EL, Goodman, MT, Gronwald, J, Karlan, BY, Kommoss, S, Menon, U, Sinn, H-P, Staebler, A, Brenton, JD, Bowtell, DD, Pharoah, PDP, Ramus, SJ, and Kobel, M
Abstract: BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
Published: 2023

5. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Author: Kobel, M, Kang, E-Y, Weir, A, Rambau, PF, Lee, C-H, Nelson, GS, Ghatage, P, Meagher, NS, Riggan, MJ, Alsop, J, Anglesio, MS, Beckmann, MW, Bisinotto, C, Boisen, M, Boros, J, Brand, AH, Brooks-Wilson, A, Carney, ME, Coulson, P, Courtney-Brooks, M, Cushing-Haugen, KL, Cybulski, C, Deen, S, El-Bahrawy, MA, Elishaev, E, Erber, R, Fereday, S, Fischer, A, Gayther, SA, Barquin-Garcia, A, Gentry-Maharaj, A, Gilks, CB, Gronwald, H, Grube, M, Harnett, PR, Harris, HR, Hartkopf, AD, Hartmann, A, Hein, A, Hendley, J, Hernandez, BY, Huang, Y, Jakubowska, A, Jimenez-Linan, M, Jones, ME, Kennedy, CJ, Kluz, T, Koziak, JM, Lesnock, J, Lester, J, Lubinski, J, Longacre, TA, Lycke, M, Mateoiu, C, McCauley, BM, McGuire, V, Ney, B, Olawaiye, A, Orsulic, S, Osorio, A, Paz-Ares, L, Ramon Y Cajal, T, Rothstein, JH, Ruebner, M, Schoemaker, MJ, Shah, M, Sharma, R, Sherman, ME, Shvetsov, YB, Singh, N, Steed, H, Storr, SJ, Talhouk, A, Traficante, N, Wang, C, Whittemore, AS, Widschwendter, M, Wilkens, LR, Winham, SJ, Benitez, J, Berchuck, A, Bowtell, DD, Candido dos Reis, FJ, Campbell, I, Cook, LS, DeFazio, A, Doherty, JA, Fasching, PA, Fortner, RT, Garcia, MJ, Goodman, MT, Goode, EL, Gronwald, J, Huntsman, DG, Karlan, BY, Kelemen, LE, Kommoss, S, Le, ND, Martin, SG, Menon, U, Modugno, F, Pharoah, PDP, Schildkraut, JM, Sieh, W, Staebler, A, Sundfeldt, K, Swerdlow, AJ, Ramus, SJ, Brenton, JD, Kobel, M, Kang, E-Y, Weir, A, Rambau, PF, Lee, C-H, Nelson, GS, Ghatage, P, Meagher, NS, Riggan, MJ, Alsop, J, Anglesio, MS, Beckmann, MW, Bisinotto, C, Boisen, M, Boros, J, Brand, AH, Brooks-Wilson, A, Carney, ME, Coulson, P, Courtney-Brooks, M, Cushing-Haugen, KL, Cybulski, C, Deen, S, El-Bahrawy, MA, Elishaev, E, Erber, R, Fereday, S, Fischer, A, Gayther, SA, Barquin-Garcia, A, Gentry-Maharaj, A, Gilks, CB, Gronwald, H, Grube, M, Harnett, PR, Harris, HR, Hartkopf, AD, Hartmann, A, Hein, A, Hendley, J, Hernandez, BY, Huang, Y, Jakubowska, A, Jimenez-Linan, M, Jones, ME, Kennedy, CJ, Kluz, T, Koziak, JM, Lesnock, J, Lester, J, Lubinski, J, Longacre, TA, Lycke, M, Mateoiu, C, McCauley, BM, McGuire, V, Ney, B, Olawaiye, A, Orsulic, S, Osorio, A, Paz-Ares, L, Ramon Y Cajal, T, Rothstein, JH, Ruebner, M, Schoemaker, MJ, Shah, M, Sharma, R, Sherman, ME, Shvetsov, YB, Singh, N, Steed, H, Storr, SJ, Talhouk, A, Traficante, N, Wang, C, Whittemore, AS, Widschwendter, M, Wilkens, LR, Winham, SJ, Benitez, J, Berchuck, A, Bowtell, DD, Candido dos Reis, FJ, Campbell, I, Cook, LS, DeFazio, A, Doherty, JA, Fasching, PA, Fortner, RT, Garcia, MJ, Goodman, MT, Goode, EL, Gronwald, J, Huntsman, DG, Karlan, BY, Kelemen, LE, Kommoss, S, Le, ND, Martin, SG, Menon, U, Modugno, F, Pharoah, PDP, Schildkraut, JM, Sieh, W, Staebler, A, Sundfeldt, K, Swerdlow, AJ, Ramus, SJ, and Brenton, JD
Abstract: Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Published: 2023

6. Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Meagher, NS, Gorringe, KL, Wakefield, M, Bolithon, A, Pang, CNI, Chiu, DS, Anglesio, MS, Mallitt, K-A, Doherty, JA, Harris, HR, Schildkraut, JM, Berchuck, A, Cushing-Haugen, KL, Chezar, K, Chou, A, Tan, A, Alsop, J, Barlow, E, Beckmann, MW, Boros, J, Bowtell, DDL, Brand, AH, Brenton, JD, Campbell, I, Cheasley, D, Cohen, J, Cybulski, C, Elishaev, E, Erber, R, Farrell, R, Fischer, A, Fu, Z, Gilks, B, Gill, AJ, Gourley, C, Grube, M, Harnett, PR, Hartmann, A, Hettiaratchi, A, Hogdall, CK, Huzarski, T, Jakubowska, A, Jimenez-Linan, M, Kennedy, CJ, Kim, B-G, Kim, J-W, Kim, J-H, Klett, K, Koziak, JM, Lai, T, Laslavic, A, Lester, J, Leung, Y, Li, N, Liauw, W, Lim, BWX, Linder, A, Lubinski, J, Mahale, S, Mateoiu, C, McInerny, S, Menkiszak, J, Minoo, P, Mittelstadt, S, Morris, D, Orsulic, S, Park, S-Y, Pearce, CL, Pearson, J, Pike, MC, Quinn, CM, Mohan, GR, Rao, J, Riggan, MJ, Ruebner, M, Salfinger, S, Scott, CL, Shah, M, Steed, H, Stewart, CJR, Subramanian, D, Sung, S, Tang, K, Timpson, P, Ward, RL, Wiedenhoefer, R, Thorne, H, Cohen, PA, Crowe, P, Fasching, PA, Gronwald, J, Hawkins, NJ, Hogdall, E, Huntsman, DG, James, PA, Karlan, BY, Kelemen, LE, Kommoss, S, Konecny, GE, Modugno, F, Park, SK, Staebler, A, Sundfeldt, K, Wu, AH, Talhouk, A, Pharoah, PDP, Anderson, L, DeFazio, A, Kobel, M, Friedlander, ML, Ramus, SJ, Meagher, NS, Gorringe, KL, Wakefield, M, Bolithon, A, Pang, CNI, Chiu, DS, Anglesio, MS, Mallitt, K-A, Doherty, JA, Harris, HR, Schildkraut, JM, Berchuck, A, Cushing-Haugen, KL, Chezar, K, Chou, A, Tan, A, Alsop, J, Barlow, E, Beckmann, MW, Boros, J, Bowtell, DDL, Brand, AH, Brenton, JD, Campbell, I, Cheasley, D, Cohen, J, Cybulski, C, Elishaev, E, Erber, R, Farrell, R, Fischer, A, Fu, Z, Gilks, B, Gill, AJ, Gourley, C, Grube, M, Harnett, PR, Hartmann, A, Hettiaratchi, A, Hogdall, CK, Huzarski, T, Jakubowska, A, Jimenez-Linan, M, Kennedy, CJ, Kim, B-G, Kim, J-W, Kim, J-H, Klett, K, Koziak, JM, Lai, T, Laslavic, A, Lester, J, Leung, Y, Li, N, Liauw, W, Lim, BWX, Linder, A, Lubinski, J, Mahale, S, Mateoiu, C, McInerny, S, Menkiszak, J, Minoo, P, Mittelstadt, S, Morris, D, Orsulic, S, Park, S-Y, Pearce, CL, Pearson, J, Pike, MC, Quinn, CM, Mohan, GR, Rao, J, Riggan, MJ, Ruebner, M, Salfinger, S, Scott, CL, Shah, M, Steed, H, Stewart, CJR, Subramanian, D, Sung, S, Tang, K, Timpson, P, Ward, RL, Wiedenhoefer, R, Thorne, H, Cohen, PA, Crowe, P, Fasching, PA, Gronwald, J, Hawkins, NJ, Hogdall, E, Huntsman, DG, James, PA, Karlan, BY, Kelemen, LE, Kommoss, S, Konecny, GE, Modugno, F, Park, SK, Staebler, A, Sundfeldt, K, Wu, AH, Talhouk, A, Pharoah, PDP, Anderson, L, DeFazio, A, Kobel, M, Friedlander, ML, and Ramus, SJ
Abstract: PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Published: 2022

7. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8(+) TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas

Author: Heinze, K, Nazeran, TM, Lee, S, Kramer, P, Cairns, ES, Chiu, DS, Leung, SCY, Kang, EY, Meagher, NS, Kennedy, CJ, Boros, J, Kommoss, F, Vollert, H-W, Heitze, F, du Bois, A, Harter, P, Grube, M, Kraemer, B, Staebler, A, Kommoss, FKF, Heublein, S, Sinn, H-P, Singh, N, Laslavic, A, Elishaev, E, Olawaiye, A, Moysich, K, Modugno, F, Sharma, R, Brand, AH, Harnett, PR, DeFazio, A, Fortner, RT, Lubinski, J, Lener, M, Toloczko-Grabarek, A, Cybulski, C, Gronwald, H, Gronwald, J, Coulson, P, El-Bahrawy, MA, Jones, ME, Schoemaker, MJ, Swerdlow, AJ, Gorringe, KL, Campbell, I, Cook, L, Gayther, SA, Carney, ME, Shvetsov, YB, Hernandez, BY, Wilkens, LR, Goodman, MT, Mateoiu, C, Linder, A, Sundfeldt, K, Kelemen, LE, Gentry-Maharaj, A, Widschwendter, M, Menon, U, Bolton, KL, Alsop, J, Shah, M, Jimenez-Linan, M, Pharoah, PDP, Brenton, JD, Cushing-Haugen, KL, Harris, HR, Doherty, JA, Gilks, B, Ghatage, P, Huntsman, DG, Nelson, GS, Tinker, A, Lee, C-H, Goode, EL, Nelson, BH, Ramus, SJ, Kommoss, S, Talhouk, A, Kobel, M, Anglesio, MS, Heinze, K, Nazeran, TM, Lee, S, Kramer, P, Cairns, ES, Chiu, DS, Leung, SCY, Kang, EY, Meagher, NS, Kennedy, CJ, Boros, J, Kommoss, F, Vollert, H-W, Heitze, F, du Bois, A, Harter, P, Grube, M, Kraemer, B, Staebler, A, Kommoss, FKF, Heublein, S, Sinn, H-P, Singh, N, Laslavic, A, Elishaev, E, Olawaiye, A, Moysich, K, Modugno, F, Sharma, R, Brand, AH, Harnett, PR, DeFazio, A, Fortner, RT, Lubinski, J, Lener, M, Toloczko-Grabarek, A, Cybulski, C, Gronwald, H, Gronwald, J, Coulson, P, El-Bahrawy, MA, Jones, ME, Schoemaker, MJ, Swerdlow, AJ, Gorringe, KL, Campbell, I, Cook, L, Gayther, SA, Carney, ME, Shvetsov, YB, Hernandez, BY, Wilkens, LR, Goodman, MT, Mateoiu, C, Linder, A, Sundfeldt, K, Kelemen, LE, Gentry-Maharaj, A, Widschwendter, M, Menon, U, Bolton, KL, Alsop, J, Shah, M, Jimenez-Linan, M, Pharoah, PDP, Brenton, JD, Cushing-Haugen, KL, Harris, HR, Doherty, JA, Gilks, B, Ghatage, P, Huntsman, DG, Nelson, GS, Tinker, A, Lee, C-H, Goode, EL, Nelson, BH, Ramus, SJ, Kommoss, S, Talhouk, A, Kobel, M, and Anglesio, MS
Published: 2022

8. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses.

Author: Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., and Houghton R.
Abstract: TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MB
Published: 2021

9. Prevalence, symptoms and sexual consequences of chronic graft-versus-host disease in the female genital tract

Author: Knutsson, E. Smith, Broman, A.-K., Björk, Y., Hallberg, D., Sundfeldt, K., Johansson, J.-E., Styrenius, M., and Brune, M.
Published: 2008

10. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author: Jiang, X., Finucane, H.K., Schumacher, F.R., Schmit, S.L., Tyrer, J.P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K.B., Dennis, J., Conti, D.V., Casey, G., Gaudet, M.M., Huyghe, J.R., Albanes, D., Aldrich, M.C., Andrew, A.S., Andrulis, I.L., Anton-Culver, H., Antoniou, A.C., Antonenkova, N.N., Arnold, S.M., Aronson, K.J., Arun, B.K., Bandera, E.V., Barkardottir, R.B., Barnes, D.R., Batra, J., Beckmann, M.W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S.I., Bickeboller, H., Bien, S.A., Blomqvist, C., Boccia, S., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Brauch, H., Brenner, H., Brenton, J.D., Brook, M.N., Brunet, J., Brunnstrom, H., Buchanan, D.D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M.A., Campbell, I., Campbell, P.T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A.L., Chan, A.T., Chang-Claude, J., Chanock, S.J., Chen, C., Christiani, D.C., Claes, K.B.M., Claessens, F., Clements, J., Collee, J.M., Correa, M.C., Couch, F.J., Cox, A., Cunningham, J.M., Cybulski, C., Czene, K., Daly, M.B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J.L., Dork, T., Duell, E.J., Dunning, A.M., Dwek, M., Eccles, D.M., Edlund, C.K., Edwards, D.R.V., Ellberg, C., Evans, D.G., Fasching, P.A., Ferris, R.L., Liloglou, T., Figueiredo, J.C., Fletcher, O., Fortner, R.T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S.J., Ganz, P.A., Garber, J., Garcia-Saenz, J.A., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Goode, E.L., Goodman, M.T., Goodman, G., Grankvist, K., Greene, M.H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F.C., Hamilton, R.J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y.C., Hopper, J.L., Houlston, R., Hulick, P.J., Hunter, D.J., Huntsman, D.G., Idos, G., Imyanitov, E.N., Ingles, S.A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M.A., Johansson, M., John, E.M., Joshi, A.D., Kaneva, R., Karlan, B.Y., Kelemen, L.E., Kuhl, T., Khaw, K.T., Khusnutdinova, E., Kibel, A.S., Kiemeney, L.A., Kim, J., Kjaer, S.K., Knight, J.A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V.N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M.T., Lazarus, P., N.D. le, Lee, E., Lejbkowicz, F., Lenz, H.J., Leslie, G., Lessel, D., Lester, J., Levine, D.A., Li, L., Li, C.I., Lindblom, A., Lindor, N.M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R.L., MacInnis, R.J., Modugno, F., Montagna, M., Moreno, V., Moysich, K.B., Mucci, L., Muir, K., Mulligan, A.M., Nathanson, K.L., Neal, D.E., Ness, A.R., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Newcomb, L.F., Nielsen, F.C., Nikitina-Zake, L., Nordestgaard, B.G., Nussbaum, R.L., Offit, K., Olah, E., Olama, A.A. al, Olopade, O.I., Olshan, A.F., Olsson, H., Osorio, A., Pandha, H., Park, J.Y., Pashayan, N., Parsons, M.T., Pejovic, T., Penney, K.L., Peters, W.H.M., Phelan, C.M., Phipps, A.I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S.J., Raskin, L., Rennert, G., Rennert, H.S., Rensburg, E.J., Riggan, M.J., Risch, H.A., Risch, A., Roobol, M.J., Rosenstein, B.S., Rossing, M.A., Ruyck, K., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schabath, M.B., Schleutker, J., Schmidt, M.K., Setiawan, V.W., Shen, H.B., Siegel, E.M., Sieh, W., Singer, C.F., Slattery, M.L., Sorensen, K.D., Southey, M.C., Spurdle, A.B., Stanford, J.L., Stevens, V.L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A.J., Tajara, E.H., Tangen, C.M., Tardon, A., Taylor, J.A., Teare, M.D., Teixeira, M.R., Terry, M.B., Terry, K.L., Thibodeau, S.N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A.E., Torres, D., Townsend, P.A., Travis, R.C., Tung, N., and Tworoger
Published: 2019

11. Gelatinases and their tissue inhibitors during human ovulation: increased expression of tissue inhibitor of matrix metalloproteinase-1

Author: Lind, A.-K., Dahm-Kähler, P., Weijdegård, B., Sundfeldt, K., and Brännström, M.
Published: 2006

12. Collagens in the human ovary and their changes in the perifollicular stroma during ovulation

Author: LIND, A. K., WEIJDEGÅRD, B., DAHM-KÄHLER, P., Mölne, J., SUNDFELDT, K., and BRÄNNSTRÖM, M.
Published: 2006
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13. Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer.

Author: Oehler M.K., Hoffmann P., Jobling T., Sundfeldt K., Stephens A.N., Klingler-Hoffmann M., Lokman N.A., Weiland F., Oehler M.K., Hoffmann P., Jobling T., Sundfeldt K., Stephens A.N., Klingler-Hoffmann M., Lokman N.A., and Weiland F.
Abstract: Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted. We performed intraoperative blood sampling from ovarian veins of stage I epithelial ovarian carcinomas and analyzed the serum proteome. Junction plakoglobin (JUP) was found to be elevated in venous blood from ovaries with malignancies when compared to those with benign disease. Peripheral plasma JUP levels were validated by ELISA in a multicenter international patient cohort. JUP was significantly increased in FIGO serous stage IA+B (1.97-fold increase; p < 0.001; n = 20), serous stage I (2.09-fold increase; p < 0.0001; n = 40), serous stage II (1.81-fold increase, p < 0.001, n = 23) and serous stage III ovarian carcinomas (1.98-fold increase; p < 0.0001; n = 34) vs. normal controls (n = 109). JUP plasma levels were not increased in early stage breast cancer (p = 0.122; n = 12). In serous ovarian cancer patients, JUP had a sensitivity of 85% in stage IA+B and 60% in stage IA-C, with specificities of 76 and 94%, respectively. A logistic regression model of JUP and Cancer Antigen 125 (CA125) revealed a sensitivity of 70% for stage IA+B and 75% for stage IA-C serous carcinomas at 100% specificity. Our novel ovarian blood sampling - proteomics approach identified JUP as a promising new biomarker for epithelial ovarian cancer, which in combination with CA125 might fulfill the test criteria for ovarian cancer screening.© Copyright © 2020 Weiland, Lokman, Klingler-Hoffmann, Jobling, Stephens, Sundfeldt, Hoffmann and Oehler.
Published: 2020

14. HUMAN OVARIAN SURFACE EPITHELIUM FOR IN VITRO CELL CULTURE - A NEW APPROACH: P271

Author: Abrahamsson, G., Ivarsson, K, Sundfeldt, K, and Janson, PO
Published: 1996

15. Shared heritability and functional enrichment across six solid cancers.

Author: Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tangen C.M., Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., and Tangen C.M.
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 x 10-8), breast and ovarian cancer (rg = 0.24, p = 7 x 10-5), breast and lung cancer (rg = 0.18, p =1.5 x 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 x 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Copyright © 2019, The Author(s).
Published: 2019

16. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4).

Author: Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., and Wu A.H.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.Copyright © 2019, The Author(s).
Published: 2019

17. Erratum: Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature communications (2019) 10 1 (431))

Author: Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Høgdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J.L. (John), Houlston, R. (Richard), Hulick, P.J. (Peter J.), Hunter, D.J. (David), Huntsman, D.G. (David G.), Idos, G. (Gregory), Imyanitov, E.N. (Evgeny), Ingles, S.A. (Sue), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Jenkins, M.A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E.M. (Esther), Joshi, A.D. (Amit D.), Kaneva, R. (Radka), Karlan, B.Y. (Beth), Kelemen, L.E. (Linda E.), Kühl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E.K. (Elza), Kibel, A. (Adam), Kiemeney, L.A. (Lambertus A.), Kim, J. (Jongoh), Kjaer, M. (Michael), Knight, J.A. (Julia), Kogevinas, M. (Manolis), Kote-Jarai, Z., Koutros, S. (Stella), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M.T. (Maria Teresa), Lazarus, P. (Philip), Le, N.D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D.A. (Douglas), Li, L. (Li), Li, C.I. (Christopher I.), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L., Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R.L. (Roger), MacInnis, R.J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Víctor), Moysich, K.B. (Kirsten), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neal, D. (David), Ness, A.R. (Andrew R.), Neuhausen, S.L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Newcomb, L.F. (Lisa F.), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E. (Edith), Olama, A.A.A. (Ali Amin Al), Olopade, O.I. (Olofunmilayo), Olshan, A.F. (Andrew F.), Olsson, H. (Håkan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J.Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. (Marilyn), Pejovic, T. (Tanja), Penney, K.L. (Kathryn L.), Peters, W.H.M. (Wilbert), Phelan, C. (Catherine), Phipps, A.I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S.J. (Susan), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rensburg, E.J. (Elizabeth) van, Riggan, M.J. (Marjorie J.), Risch, H.A. (Harvey A.), Risch, A. (Angela), Roobol, M.J. (Monique J.), Rosenstein, B.S. (Barry S.), Rossing, M.A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Sawyer, E.J. (Elinor J.), Schabath, M.B. (Matthew), Schleutker, J. (Johanna), Schmidt, M.K. (Marjanka), Setiawan, V.W. (V Wendy), Shen, H. (Hongbing), Siegel, E.M. (Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), Lindström, S. (Sara), Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Høgdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J.L. (John), Houlston, R. (Richard), Hulick, P.J. (Peter J.), Hunter, D.J. (David), Huntsman, D.G. (David G.), Idos, G. (Gregory), Imyanitov, E.N. (Evgeny), Ingles, S.A. (Sue), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Jenkins, M.A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E.M. (Esther), Joshi, A.D. (Amit D.), Kaneva, R. (Radka), Karlan, B.Y. (Beth), Kelemen, L.E. (Linda E.), Kühl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E.K. (Elza), Kibel, A. (Adam), Kiemeney, L.A. (Lambertus A.), Kim, J. (Jongoh), Kjaer, M. (Michael), Knight, J.A. (Julia), Kogevinas, M. (Manolis), Kote-Jarai, Z., Koutros, S. (Stella), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M.T. (Maria Teresa), Lazarus, P. (Philip), Le, N.D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D.A. (Douglas), Li, L. (Li), Li, C.I. (Christopher I.), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L., Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R.L. (Roger), MacInnis, R.J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Víctor), Moysich, K.B. (Kirsten), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neal, D. (David), Ness, A.R. (Andrew R.), Neuhausen, S.L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Newcomb, L.F. (Lisa F.), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E. (Edith), Olama, A.A.A. (Ali Amin Al), Olopade, O.I. (Olofunmilayo), Olshan, A.F. (Andrew F.), Olsson, H. (Håkan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J.Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. (Marilyn), Pejovic, T. (Tanja), Penney, K.L. (Kathryn L.), Peters, W.H.M. (Wilbert), Phelan, C. (Catherine), Phipps, A.I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S.J. (Susan), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rensburg, E.J. (Elizabeth) van, Riggan, M.J. (Marjorie J.), Risch, H.A. (Harvey A.), Risch, A. (Angela), Roobol, M.J. (Monique J.), Rosenstein, B.S. (Barry S.), Rossing, M.A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Sawyer, E.J. (Elinor J.), Schabath, M.B. (Matthew), Schleutker, J. (Johanna), Schmidt, M.K. (Marjanka), Setiawan, V.W. (V Wendy), Shen, H. (Hongbing), Siegel, E.M. (Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), and Lindström, S. (Sara)
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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18. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J, Conti, DV, Casey, G, Gaudet, MM, Huyghe, JR, Albanes, D, Aldrich, MC, Andrew, AS, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Antonenkova, NN, Arnold, SM, Aronson, KJ, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Batra, J, Beckmann, MW, Benitez, J, Benlloch, S, Berchuck, A, Berndt, SI, Bickeboeller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnstrom, H, Buchanan, DD, Burwinkel, B, Butzow, R, Cadoni, G, Caldes, T, Caligo, MA, Campbell, I, Campbell, PT, Cancel-Tassin, G, Cannon-Albright, L, Campa, D, Caporaso, N, Carvalho, AL, Chan, AT, Chang-Claude, J, Chanock, SJ, Chen, C, Christiani, DC, Claes, KBM, Claessens, F, Clements, J, Collee, JM, Correa, MC, Couch, FJ, Cox, A, Cunningham, JM, Cybulski, C, Czene, K, Daly, MB, defazio, A, Devilee, P, Diez, O, Gago-Dominguez, M, Donovan, JL, Doerk, T, Duell, EJ, Dunning, AM, Dwek, M, Eccles, DM, Edlund, CK, Edwards, DRV, Ellberg, C, Evans, DG, Fasching, PA, Ferris, RL, Liloglou, T, Figueiredo, JC, Fletcher, O, Fortner, RT, Fostira, F, Franceschi, S, Friedman, E, Gallinger, SJ, Ganz, PA, Garber, J, Garcia-Saenz, JA, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Goode, EL, Goodman, MT, Goodman, G, Grankvist, K, Greene, MH, Gronberg, H, Gronwald, J, Guenel, P, Hakansson, N, Hall, P, Hamann, U, Hamdy, FC, Hamilton, RJ, Hampe, J, Haugen, A, Heitz, F, Herrero, R, Hillemanns, P, Hoffmeister, M, Hogdall, E, Hong, Y-C, Hopper, JL, Houlston, R, Hulick, PJ, Hunter, DJ, Huntsman, DG, Idos, G, Imyanitov, EN, Ingles, SA, Isaacs, C, Jakubowska, A, James, P, Jenkins, MA, Johansson, M, John, EM, Joshi, AD, Kaneva, R, Karlan, BY, Kelemen, LE, Kuhl, T, Khaw, K-T, Khusnutdinova, E, Kibel, AS, Kiemeney, LA, Kim, J, Kjaer, SK, Knight, JA, Kogevinas, M, Kote-Jarai, Z, Koutros, S, Kristensen, VN, Kupryjanczyk, J, Lacko, M, Lam, S, Lambrechts, D, Landi, MT, Lazarus, P, Le, ND, Lee, E, Lejbkowicz, F, Lenz, H-J, Leslie, G, Lessel, D, Lester, J, Levine, DA, Li, L, Li, CI, Lindblom, A, Lindor, NM, Liu, G, Loupakis, F, Lubinski, J, Maehle, L, Maier, C, Mannermaa, A, Le Marchand, L, Margolin, S, May, T, McGuffog, L, Meindl, A, Middha, P, Miller, A, Milne, RL, MacInnis, RJ, Modugno, F, Montagna, M, Moreno, V, Moysich, KB, Mucci, L, Muir, K, Mulligan, AM, Nathanson, KL, Neal, DE, Ness, AR, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Newcomb, LF, Nielsen, FC, Nikitina-Zake, L, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Al Olama, AA, Olopade, OI, Olshan, AF, Olsson, H, Osorio, A, Pandha, H, Park, JY, Pashayan, N, Parsons, MT, Pejovic, T, Penney, KL, Peters, WHM, Phelan, CM, Phipps, AI, Plaseska-Karanfilska, D, Pring, M, Prokofyeva, D, Radice, P, Stefansson, K, Ramus, SJ, Raskin, L, Rennert, G, Rennert, HS, van Rensburg, EJ, Riggan, MJ, Risch, HA, Risch, A, Roobol, MJ, Rosenstein, BS, Rossing, MA, De Ruyck, K, Saloustros, E, Sandler, DP, Sawyer, EJ, Schabath, MB, Schleutker, J, Schmidt, MK, Setiawan, VW, Shen, H, Siegel, EM, Sieh, W, Singer, CF, Slattery, ML, Sorensen, KD, Southey, MC, Spurdle, AB, Stanford, JL, Stevens, VL, Stintzing, S, Stone, J, Sundfeldt, K, Sutphen, R, Swerdlow, AJ, Tajara, EH, Tangen, CM, Tardon, A, Taylor, JA, Teare, MD, Teixeira, MR, Terry, MB, Terry, KL, Thibodeau, SN, Thomassen, M, Bjorge, L, Tischkowitz, M, Toland, AE, Torres, D, Townsend, PA, Travis, RC, Tung, N, Tworoger, SS, Ulrich, CM, Usmani, N, Vachon, CM, Van Nieuwenhuysen, E, Vega, A, Aguado-Barrera, ME, Wang, Q, Webb, PM, Weinberg, CR, Weinstein, S, Weissler, MC, Weitzel, JN, West, CML, White, E, Whittemore, AS, Wichmann, H-E, Wiklund, F, Winqvist, R, Wolk, A, Woll, P, Woods, M, Wu, AH, Wu, X, Yannoukakos, D, Zheng, W, Zienolddiny, S, Ziogas, A, Zorn, KK, Lane, JM, Saxena, R, Thomas, D, Hung, RJ, Diergaarde, B, Mckay, J, Peters, U, Hsu, L, Garcia-Closas, M, Eeles, RA, Chenevix-Trench, G, Brennan, PJ, Haiman, CA, Simard, J, Easton, DF, Gruber, SB, Pharoah, PDP, Price, AL, Pasaniuc, B, Amos, CI, Kraft, P, Lindstrom, S, Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J, Conti, DV, Casey, G, Gaudet, MM, Huyghe, JR, Albanes, D, Aldrich, MC, Andrew, AS, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Antonenkova, NN, Arnold, SM, Aronson, KJ, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Batra, J, Beckmann, MW, Benitez, J, Benlloch, S, Berchuck, A, Berndt, SI, Bickeboeller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnstrom, H, Buchanan, DD, Burwinkel, B, Butzow, R, Cadoni, G, Caldes, T, Caligo, MA, Campbell, I, Campbell, PT, Cancel-Tassin, G, Cannon-Albright, L, Campa, D, Caporaso, N, Carvalho, AL, Chan, AT, Chang-Claude, J, Chanock, SJ, Chen, C, Christiani, DC, Claes, KBM, Claessens, F, Clements, J, Collee, JM, Correa, MC, Couch, FJ, Cox, A, Cunningham, JM, Cybulski, C, Czene, K, Daly, MB, defazio, A, Devilee, P, Diez, O, Gago-Dominguez, M, Donovan, JL, Doerk, T, Duell, EJ, Dunning, AM, Dwek, M, Eccles, DM, Edlund, CK, Edwards, DRV, Ellberg, C, Evans, DG, Fasching, PA, Ferris, RL, Liloglou, T, Figueiredo, JC, Fletcher, O, Fortner, RT, Fostira, F, Franceschi, S, Friedman, E, Gallinger, SJ, Ganz, PA, Garber, J, Garcia-Saenz, JA, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Goode, EL, Goodman, MT, Goodman, G, Grankvist, K, Greene, MH, Gronberg, H, Gronwald, J, Guenel, P, Hakansson, N, Hall, P, Hamann, U, Hamdy, FC, Hamilton, RJ, Hampe, J, Haugen, A, Heitz, F, Herrero, R, Hillemanns, P, Hoffmeister, M, Hogdall, E, Hong, Y-C, Hopper, JL, Houlston, R, Hulick, PJ, Hunter, DJ, Huntsman, DG, Idos, G, Imyanitov, EN, Ingles, SA, Isaacs, C, Jakubowska, A, James, P, Jenkins, MA, Johansson, M, John, EM, Joshi, AD, Kaneva, R, Karlan, BY, Kelemen, LE, Kuhl, T, Khaw, K-T, Khusnutdinova, E, Kibel, AS, Kiemeney, LA, Kim, J, Kjaer, SK, Knight, JA, Kogevinas, M, Kote-Jarai, Z, Koutros, S, Kristensen, VN, Kupryjanczyk, J, Lacko, M, Lam, S, Lambrechts, D, Landi, MT, Lazarus, P, Le, ND, Lee, E, Lejbkowicz, F, Lenz, H-J, Leslie, G, Lessel, D, Lester, J, Levine, DA, Li, L, Li, CI, Lindblom, A, Lindor, NM, Liu, G, Loupakis, F, Lubinski, J, Maehle, L, Maier, C, Mannermaa, A, Le Marchand, L, Margolin, S, May, T, McGuffog, L, Meindl, A, Middha, P, Miller, A, Milne, RL, MacInnis, RJ, Modugno, F, Montagna, M, Moreno, V, Moysich, KB, Mucci, L, Muir, K, Mulligan, AM, Nathanson, KL, Neal, DE, Ness, AR, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Newcomb, LF, Nielsen, FC, Nikitina-Zake, L, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Al Olama, AA, Olopade, OI, Olshan, AF, Olsson, H, Osorio, A, Pandha, H, Park, JY, Pashayan, N, Parsons, MT, Pejovic, T, Penney, KL, Peters, WHM, Phelan, CM, Phipps, AI, Plaseska-Karanfilska, D, Pring, M, Prokofyeva, D, Radice, P, Stefansson, K, Ramus, SJ, Raskin, L, Rennert, G, Rennert, HS, van Rensburg, EJ, Riggan, MJ, Risch, HA, Risch, A, Roobol, MJ, Rosenstein, BS, Rossing, MA, De Ruyck, K, Saloustros, E, Sandler, DP, Sawyer, EJ, Schabath, MB, Schleutker, J, Schmidt, MK, Setiawan, VW, Shen, H, Siegel, EM, Sieh, W, Singer, CF, Slattery, ML, Sorensen, KD, Southey, MC, Spurdle, AB, Stanford, JL, Stevens, VL, Stintzing, S, Stone, J, Sundfeldt, K, Sutphen, R, Swerdlow, AJ, Tajara, EH, Tangen, CM, Tardon, A, Taylor, JA, Teare, MD, Teixeira, MR, Terry, MB, Terry, KL, Thibodeau, SN, Thomassen, M, Bjorge, L, Tischkowitz, M, Toland, AE, Torres, D, Townsend, PA, Travis, RC, Tung, N, Tworoger, SS, Ulrich, CM, Usmani, N, Vachon, CM, Van Nieuwenhuysen, E, Vega, A, Aguado-Barrera, ME, Wang, Q, Webb, PM, Weinberg, CR, Weinstein, S, Weissler, MC, Weitzel, JN, West, CML, White, E, Whittemore, AS, Wichmann, H-E, Wiklund, F, Winqvist, R, Wolk, A, Woll, P, Woods, M, Wu, AH, Wu, X, Yannoukakos, D, Zheng, W, Zienolddiny, S, Ziogas, A, Zorn, KK, Lane, JM, Saxena, R, Thomas, D, Hung, RJ, Diergaarde, B, Mckay, J, Peters, U, Hsu, L, Garcia-Closas, M, Eeles, RA, Chenevix-Trench, G, Brennan, PJ, Haiman, CA, Simard, J, Easton, DF, Gruber, SB, Pharoah, PDP, Price, AL, Pasaniuc, B, Amos, CI, Kraft, P, and Lindstrom, S
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
Published: 2019

19. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author: Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J, Conti, DV, Casey, G, Gaudet, MM, Huyghe, JR, Albanes, D, Aldrich, MC, Andrew, AS, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Antonenkova, NN, Arnold, SM, Aronson, KJ, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Batra, J, Beckmann, MW, Benitez, J, Benlloch, S, Berchuck, A, Berndt, SI, Bickeboller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnstrom, H, Buchanan, DD, Burwinkel, B, Butzow, R, Cadoni, G, Caldes, T, Caligo, MA, Campbell, I, Campbell, PT, Cancel-Tassin, G, Cannon-Albright, L, Campa, D, Caporaso, N, Carvalho, AL, Chan, AT, Chang-Claude, J, Chanock, SJ, Chen, C, Christiani, DC, Claes, KBM, Claessens, F, Clements, J, Collee, JM, Correa, MC, Couch, FJ, Cox, A, Cunningham, JM, Cybulski, C, Czene, K, Daly, MB, deFazio, A, Devilee, P, Diez, O, Gago-Dominguez, M, Donovan, JL, Dork, T, Duell, EJ, Dunning, AM, Dwek, M, Eccles, DM, Edlund, CK, Edwards, DRV, Ellberg, C, Evans, DG, Fasching, PA, Ferris, RL, Liloglou, T, Figueiredo, JC, Fletcher, O, Fortner, RT, Fostira, F, Franceschi, S, Friedman, E, Gallinger, SJ, Ganz, PA, Garber, J, Garcia-Saenz, JA, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Goode, EL, Goodman, MT, Goodman, G, Grankvist, K, Greene, MH, Gronberg, H, Gronwald, J, Guenel, P, Hakansson, N, Hall, P, Hamann, U, Hamdy, FC, Hamilton, RJ, Hampe, J, Haugen, A, Heitz, F, Herrero, R, Hillemanns, P, Hoffmeister, M, Hogdall, E, Hong, Y-C, Hopper, JL, Houlston, R, Hulick, PJ, Hunter, DJ, Huntsman, DG, Idos, G, Imyanitov, EN, Ingles, SA, Isaacs, C, Jakubowska, A, James, P, Jenkins, MA, Johansson, M, John, EM, Joshi, AD, Kaneva, R, Karlan, BY, Kelemen, LE, Kuehl, T, Khaw, K-T, Khusnutdinova, E, Kibel, AS, Kiemeney, LA, Kim, J, Kjaer, SK, Knight, JA, Kogevinas, M, Kote-Jarai, Z, Koutros, S, Kristensen, VN, Kupryjanczyk, J, Lacko, M, Lam, S, Lambrechts, D, Landi, MT, Lazarus, P, Le, ND, Lee, E, Lejbkowicz, F, Lenz, H-J, Leslie, G, Lessel, D, Lester, J, Levine, DA, Li, L, Li, CI, Lindblom, A, Lindor, NM, Liu, G, Loupakis, F, Lubinski, J, Maehle, L, Maier, C, Mannermaa, A, Le Marchand, L, Margolin, S, May, T, McGuffog, L, Meindl, A, Middha, P, Miller, A, Milne, RL, MacInnis, RJ, Modugno, F, Montagna, M, Moreno, V, Moysich, KB, Mucci, L, Muir, K, Mulligan, AM, Nathanson, KL, Neal, DE, Ness, AR, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Newcomb, LF, Nielsen, FC, Nikitina-Zake, L, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Al Olama, AA, Olopade, OI, Olshan, AF, Olsson, H, Osorio, A, Pandha, H, Park, JY, Pashayan, N, Parsons, MT, Pejovic, T, Penney, KL, Peters, WHM, Phelan, CM, Phipps, AI, Plaseska-Karanfilska, D, Pring, M, Prokofyeva, D, Radice, P, Stefansson, K, Ramus, SJ, Raskin, L, Rennert, G, Rennert, HS, van Rensburg, EJ, Riggan, MJ, Risch, HA, Risch, A, Roobol, MJ, Rosenstein, BS, Rossing, MA, De Ruyck, K, Saloustros, E, Sandler, DP, Sawyer, EJ, Schabath, MB, Schleutker, J, Schmidt, MK, Setiawan, VW, Shen, H, Siegel, EM, Sieh, W, Singer, CF, Slattery, ML, Sorensen, KD, Southey, MC, Spurdle, AB, Stanford, JL, Stevens, VL, Stintzing, S, Stone, J, Sundfeldt, K, Sutphen, R, Swerdlow, AJ, Tajara, EH, Tangen, CM, Tardon, A, Taylor, JA, Teare, MD, Teixeira, MR, Terry, MB, Terry, KL, Thibodeau, SN, Thomassen, M, Bjorge, L, Tischkowitz, M, Toland, AE, Torres, D, Townsend, PA, Travis, RC, Tung, N, Tworoger, SS, Ulrich, CM, Usmani, N, Vachon, CM, Van Nieuwenhuysen, E, Vega, A, Elias Aguado-Barrera, M, Wang, Q, Webb, PM, Weinberg, CR, Weinstein, S, Weissler, MC, Weitzel, JN, West, CML, White, E, Whittemore, AS, Wichmann, H-E, Wiklund, F, Winqvist, R, Wolk, A, Woll, P, Woods, M, Wu, AH, Wu, X, Yannoukakos, D, Zheng, W, Zienolddiny, S, Ziogas, A, Zorn, KK, Lane, JM, Saxena, R, Thomas, D, Hung, RJ, Diergaarde, B, McKay, J, Peters, U, Hsu, L, Garcia-Closas, M, Eeles, RA, Chenevix-Trench, G, Brennan, PJ, Haiman, CA, Simard, J, Easton, DF, Gruber, SB, Pharoah, PDP, Price, AL, Pasaniuc, B, Amos, CI, Kraft, P, Lindstrom, S, Jiang, X, Finucane, HK, Schumacher, FR, Schmit, SL, Tyrer, JP, Han, Y, Michailidou, K, Lesseur, C, Kuchenbaecker, KB, Dennis, J, Conti, DV, Casey, G, Gaudet, MM, Huyghe, JR, Albanes, D, Aldrich, MC, Andrew, AS, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Antonenkova, NN, Arnold, SM, Aronson, KJ, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Batra, J, Beckmann, MW, Benitez, J, Benlloch, S, Berchuck, A, Berndt, SI, Bickeboller, H, Bien, SA, Blomqvist, C, Boccia, S, Bogdanova, NV, Bojesen, SE, Bolla, MK, Brauch, H, Brenner, H, Brenton, JD, Brook, MN, Brunet, J, Brunnstrom, H, Buchanan, DD, Burwinkel, B, Butzow, R, Cadoni, G, Caldes, T, Caligo, MA, Campbell, I, Campbell, PT, Cancel-Tassin, G, Cannon-Albright, L, Campa, D, Caporaso, N, Carvalho, AL, Chan, AT, Chang-Claude, J, Chanock, SJ, Chen, C, Christiani, DC, Claes, KBM, Claessens, F, Clements, J, Collee, JM, Correa, MC, Couch, FJ, Cox, A, Cunningham, JM, Cybulski, C, Czene, K, Daly, MB, deFazio, A, Devilee, P, Diez, O, Gago-Dominguez, M, Donovan, JL, Dork, T, Duell, EJ, Dunning, AM, Dwek, M, Eccles, DM, Edlund, CK, Edwards, DRV, Ellberg, C, Evans, DG, Fasching, PA, Ferris, RL, Liloglou, T, Figueiredo, JC, Fletcher, O, Fortner, RT, Fostira, F, Franceschi, S, Friedman, E, Gallinger, SJ, Ganz, PA, Garber, J, Garcia-Saenz, JA, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Goode, EL, Goodman, MT, Goodman, G, Grankvist, K, Greene, MH, Gronberg, H, Gronwald, J, Guenel, P, Hakansson, N, Hall, P, Hamann, U, Hamdy, FC, Hamilton, RJ, Hampe, J, Haugen, A, Heitz, F, Herrero, R, Hillemanns, P, Hoffmeister, M, Hogdall, E, Hong, Y-C, Hopper, JL, Houlston, R, Hulick, PJ, Hunter, DJ, Huntsman, DG, Idos, G, Imyanitov, EN, Ingles, SA, Isaacs, C, Jakubowska, A, James, P, Jenkins, MA, Johansson, M, John, EM, Joshi, AD, Kaneva, R, Karlan, BY, Kelemen, LE, Kuehl, T, Khaw, K-T, Khusnutdinova, E, Kibel, AS, Kiemeney, LA, Kim, J, Kjaer, SK, Knight, JA, Kogevinas, M, Kote-Jarai, Z, Koutros, S, Kristensen, VN, Kupryjanczyk, J, Lacko, M, Lam, S, Lambrechts, D, Landi, MT, Lazarus, P, Le, ND, Lee, E, Lejbkowicz, F, Lenz, H-J, Leslie, G, Lessel, D, Lester, J, Levine, DA, Li, L, Li, CI, Lindblom, A, Lindor, NM, Liu, G, Loupakis, F, Lubinski, J, Maehle, L, Maier, C, Mannermaa, A, Le Marchand, L, Margolin, S, May, T, McGuffog, L, Meindl, A, Middha, P, Miller, A, Milne, RL, MacInnis, RJ, Modugno, F, Montagna, M, Moreno, V, Moysich, KB, Mucci, L, Muir, K, Mulligan, AM, Nathanson, KL, Neal, DE, Ness, AR, Neuhausen, SL, Nevanlinna, H, Newcomb, PA, Newcomb, LF, Nielsen, FC, Nikitina-Zake, L, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Al Olama, AA, Olopade, OI, Olshan, AF, Olsson, H, Osorio, A, Pandha, H, Park, JY, Pashayan, N, Parsons, MT, Pejovic, T, Penney, KL, Peters, WHM, Phelan, CM, Phipps, AI, Plaseska-Karanfilska, D, Pring, M, Prokofyeva, D, Radice, P, Stefansson, K, Ramus, SJ, Raskin, L, Rennert, G, Rennert, HS, van Rensburg, EJ, Riggan, MJ, Risch, HA, Risch, A, Roobol, MJ, Rosenstein, BS, Rossing, MA, De Ruyck, K, Saloustros, E, Sandler, DP, Sawyer, EJ, Schabath, MB, Schleutker, J, Schmidt, MK, Setiawan, VW, Shen, H, Siegel, EM, Sieh, W, Singer, CF, Slattery, ML, Sorensen, KD, Southey, MC, Spurdle, AB, Stanford, JL, Stevens, VL, Stintzing, S, Stone, J, Sundfeldt, K, Sutphen, R, Swerdlow, AJ, Tajara, EH, Tangen, CM, Tardon, A, Taylor, JA, Teare, MD, Teixeira, MR, Terry, MB, Terry, KL, Thibodeau, SN, Thomassen, M, Bjorge, L, Tischkowitz, M, Toland, AE, Torres, D, Townsend, PA, Travis, RC, Tung, N, Tworoger, SS, Ulrich, CM, Usmani, N, Vachon, CM, Van Nieuwenhuysen, E, Vega, A, Elias Aguado-Barrera, M, Wang, Q, Webb, PM, Weinberg, CR, Weinstein, S, Weissler, MC, Weitzel, JN, West, CML, White, E, Whittemore, AS, Wichmann, H-E, Wiklund, F, Winqvist, R, Wolk, A, Woll, P, Woods, M, Wu, AH, Wu, X, Yannoukakos, D, Zheng, W, Zienolddiny, S, Ziogas, A, Zorn, KK, Lane, JM, Saxena, R, Thomas, D, Hung, RJ, Diergaarde, B, McKay, J, Peters, U, Hsu, L, Garcia-Closas, M, Eeles, RA, Chenevix-Trench, G, Brennan, PJ, Haiman, CA, Simard, J, Easton, DF, Gruber, SB, Pharoah, PDP, Price, AL, Pasaniuc, B, Amos, CI, Kraft, P, and Lindstrom, S
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019

20. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, X. (Xia), Finucane, H. K. (Hilary K.), Schumacher, F. R. (Fredrick R.), Schmit, S. L. (Stephanie L.), Tyrer, J. P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K. B. (Karoline B.), Dennis, J. (Joe), Conti, D. V. (David V.), Casey, G. (Graham), Gaudet, M. M. (Mia M.), Huyghe, J. R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M. C. (Melinda C.), Andrew, A. S. (Angeline S.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A. C. (Antonis C.), Antonenkova, N. N. (Natalia N.), Arnold, S. M. (Susanne M.), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Bandera, E. V. (Elisa V.), Barkardottir, R. B. (Rosa B.), Barnes, D. R. (Daniel R.), Batra, J. (Jyotsna), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S. I. (Sonja I.), Bickeboeller, H. (Heike), Bien, S. A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J. D. (James D.), Brook, M. N. (Mark N.), Brunet, J. (Joan), Brunnstrom, H. (Hans), Buchanan, D. D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campbell, I. (Ian), Campbell, P. T. (Peter T.), Cancel-Tassin, G. (Geraldine), Cannon-Albright, L. (Lisa), Campa, D. (Daniele), Caporaso, N. (Neil), Carvalho, A. L. (Andre L.), Chan, A. T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chen, C. (Chu), Christiani, D. C. (David C.), Claes, K. B. (Kathleen B. M.), Claessens, F. (Frank), Clements, J. (Judith), Collee, J. M. (J. Margriet), Correa, M. C. (Marcia Cruz), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cunningham, J. M. (Julie M.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M. B. (Mary B.), defazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J. L. (Jenny L.), Doerk, T. (Thilo), Duell, E. J. (Eric J.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Edlund, C. K. (Christopher K.), Edwards, D. R. (Digna R. Velez), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Ferris, R. L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J. C. (Jane C.), Fletcher, O. (Olivia), Fortner, R. T. (Renee T.), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. J. (Steven J.), Ganz, P. A. (Patricia A.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Goode, E. L. (Ellen L.), Goodman, M. T. (Marc T.), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M. H. (Mark H.), Gronberg, H. (Henrik), Gronwald, J. (Jacek), Guenel, P. (Pascal), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. C. (Freddie C.), Hamilton, R. J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Hogdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J. L. (John L.), Houlston, R. (Richard), Hulick, P. J. (Peter J.), Hunter, D. J. (David J.), Huntsman, D. G. (David G.), Idos, G. (Gregory), Imyanitov, E. N. (Evgeny N.), Ingles, S. A. (Sue Ann), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, P. (Paul), Jenkins, M. A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E. M. (Esther M.), Joshi, A. D. (Amit D.), Kaneva, R. (Radka), Karlan, B. Y. (Beth Y.), Kelemen, L. E. (Linda E.), Kuhl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E. (Elza), Kibel, A. S. (Adam S.), Kiemeney, L. A. (Lambertus A.), Kim, J. (Jeri), Kjaer, S. K. (Susanne K.), Knight, J. A. (Julia A.), Kogevinas, M. (Manolis), Kote-Jarai, Z. (Zsofia), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M. T. (Maria Teresa), Lazarus, P. (Philip), Le, N. D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D. A. (Douglas A.), Li, L. (Li), Li, C. I. (Christopher I.), Lindblom, A. (Annika), Lindor, N. M. (Noralane M.), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L. (Lovise), Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R. L. (Roger L.), MacInnis, R. J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Victor), Moysich, K. B. (Kirsten B.), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neal, D. E. (David E.), Ness, A. R. (Andrew R.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. A. (Polly A.), Newcomb, L. F. (Lisa F.), Nielsen, F. C. (Finn Cilius), Nikitina-Zake, L. (Liene), Nordestgaard, B. G. (Borge G.), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Al Olama, A. A. (Ali Amin), Olopade, O. I. (Olufunmilayo I.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J. Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. T. (Michael T.), Pejovic, T. (Tanja), Penney, K. L. (Kathryn L.), Peters, W. H. (Wilbert H. M.), Phelan, C. M. (Catherine M.), Phipps, A. I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S. J. (Susan J.), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), van Rensburg, E. J. (Elizabeth J.), Riggan, M. J. (Marjorie J.), Risch, H. A. (Harvey A.), Risch, A. (Angela), Roobol, M. J. (Monique J.), Rosenstein, B. S. (Barry S.), Rossing, M. A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schabath, M. B. (Matthew B.), Schleutker, J. (Johanna), Schmidt, M. K. (Marjanka K.), Setiawan, V. W. (V. Wendy), Shen, H. (Hongbing), Siegel, E. M. (Erin M.), Sieh, W. (Weiva), Singer, C. F. (Christian F.), Slattery, M. L. (Martha L.), Sorensen, K. D. (Karina Dalsgaard), Southey, M. C. (Melissa C.), Spurdle, A. B. (Amanda B.), Stanford, J. L. (Janet L.), Stevens, V. L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A. J. (Anthony J.), Tajara, E. H. (Eloiza H.), Tangen, C. M. (Catherine M.), Tardon, A. (Adonina), Taylor, J. A. (Jack A.), Teare, M. D. (M. Dawn), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Terry, K. L. (Kathryn L.), Thibodeau, S. N. (Stephen N.), Thomassen, M. (Mads), Bjorge, L. (Line), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Townsend, P. A. (Paul A.), Travis, R. C. (Ruth C.), Tung, N. (Nadine), Tworoger, S. S. (Shelley S.), Ulrich, C. M. (Cornelia M.), Usmani, N. (Nawaid), Vachon, C. M. (Celine M.), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M. E. (Miguel Elias), Wang, Q. (Qin), Webb, P. M. (Penelope M.), Weinberg, C. R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M. C. (Mark C.), Weitzel, J. N. (Jeffrey N.), West, C. M. (Catharine M. L.), White, E. (Emily), Whittemore, A. S. (Alice S.), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, A. (Alicja), Woll, P. (Penella), Woods, M. (Michael), Wu, A. H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K. K. (Kristin K.), Lane, J. M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D. (Duncan), Hung, R. J. (Rayjean J.), Diergaarde, B. (Brenda), Mckay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), Garcia-Closas, M. (Montserrat), Eeles, R. A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P. J. (Paul J.), Haiman, C. A. (Christopher A.), Simard, J. (Jacques), Easton, D. F. (Douglas F.), Gruber, S. B. (Stephen B.), Pharoah, P. D. (Paul D. P.), Price, A. L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C. I. (Christopher I.), Kraft, P. (Peter), Lindstrom, S. (Sara), Jiang, X. (Xia), Finucane, H. K. (Hilary K.), Schumacher, F. R. (Fredrick R.), Schmit, S. L. (Stephanie L.), Tyrer, J. P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K. B. (Karoline B.), Dennis, J. (Joe), Conti, D. V. (David V.), Casey, G. (Graham), Gaudet, M. M. (Mia M.), Huyghe, J. R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M. C. (Melinda C.), Andrew, A. S. (Angeline S.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A. C. (Antonis C.), Antonenkova, N. N. (Natalia N.), Arnold, S. M. (Susanne M.), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Bandera, E. V. (Elisa V.), Barkardottir, R. B. (Rosa B.), Barnes, D. R. (Daniel R.), Batra, J. (Jyotsna), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S. I. (Sonja I.), Bickeboeller, H. (Heike), Bien, S. A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J. D. (James D.), Brook, M. N. (Mark N.), Brunet, J. (Joan), Brunnstrom, H. (Hans), Buchanan, D. D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Campbell, I. (Ian), Campbell, P. T. (Peter T.), Cancel-Tassin, G. (Geraldine), Cannon-Albright, L. (Lisa), Campa, D. (Daniele), Caporaso, N. (Neil), Carvalho, A. L. (Andre L.), Chan, A. T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Chen, C. (Chu), Christiani, D. C. (David C.), Claes, K. B. (Kathleen B. M.), Claessens, F. (Frank), Clements, J. (Judith), Collee, J. M. (J. Margriet), Correa, M. C. (Marcia Cruz), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cunningham, J. M. (Julie M.), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M. B. (Mary B.), defazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J. L. (Jenny L.), Doerk, T. (Thilo), Duell, E. J. (Eric J.), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Edlund, C. K. (Christopher K.), Edwards, D. R. (Digna R. Velez), Ellberg, C. (Carolina), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Ferris, R. L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J. C. (Jane C.), Fletcher, O. (Olivia), Fortner, R. T. (Renee T.), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. J. (Steven J.), Ganz, P. A. (Patricia A.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Goode, E. L. (Ellen L.), Goodman, M. T. (Marc T.), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M. H. (Mark H.), Gronberg, H. (Henrik), Gronwald, J. (Jacek), Guenel, P. (Pascal), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. C. (Freddie C.), Hamilton, R. J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Hogdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J. L. (John L.), Houlston, R. (Richard), Hulick, P. J. (Peter J.), Hunter, D. J. (David J.), Huntsman, D. G. (David G.), Idos, G. (Gregory), Imyanitov, E. N. (Evgeny N.), Ingles, S. A. (Sue Ann), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, P. (Paul), Jenkins, M. A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E. M. (Esther M.), Joshi, A. D. (Amit D.), Kaneva, R. (Radka), Karlan, B. Y. (Beth Y.), Kelemen, L. E. (Linda E.), Kuhl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E. (Elza), Kibel, A. S. (Adam S.), Kiemeney, L. A. (Lambertus A.), Kim, J. (Jeri), Kjaer, S. K. (Susanne K.), Knight, J. A. (Julia A.), Kogevinas, M. (Manolis), Kote-Jarai, Z. (Zsofia), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M. T. (Maria Teresa), Lazarus, P. (Philip), Le, N. D. (Nhu D.), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lenz, H.-J. (Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D. A. (Douglas A.), Li, L. (Li), Li, C. I. (Christopher I.), Lindblom, A. (Annika), Lindor, N. M. (Noralane M.), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L. (Lovise), Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R. L. (Roger L.), MacInnis, R. J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Victor), Moysich, K. B. (Kirsten B.), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A. M. (Anna Marie), Nathanson, K. L. (Katherine L.), Neal, D. E. (David E.), Ness, A. R. (Andrew R.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. A. (Polly A.), Newcomb, L. F. (Lisa F.), Nielsen, F. C. (Finn Cilius), Nikitina-Zake, L. (Liene), Nordestgaard, B. G. (Borge G.), Nussbaum, R. L. (Robert L.), Offit, K. (Kenneth), Olah, E. (Edith), Al Olama, A. A. (Ali Amin), Olopade, O. I. (Olufunmilayo I.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J. Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. T. (Michael T.), Pejovic, T. (Tanja), Penney, K. L. (Kathryn L.), Peters, W. H. (Wilbert H. M.), Phelan, C. M. (Catherine M.), Phipps, A. I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S. J. (Susan J.), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), van Rensburg, E. J. (Elizabeth J.), Riggan, M. J. (Marjorie J.), Risch, H. A. (Harvey A.), Risch, A. (Angela), Roobol, M. J. (Monique J.), Rosenstein, B. S. (Barry S.), Rossing, M. A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schabath, M. B. (Matthew B.), Schleutker, J. (Johanna), Schmidt, M. K. (Marjanka K.), Setiawan, V. W. (V. Wendy), Shen, H. (Hongbing), Siegel, E. M. (Erin M.), Sieh, W. (Weiva), Singer, C. F. (Christian F.), Slattery, M. L. (Martha L.), Sorensen, K. D. (Karina Dalsgaard), Southey, M. C. (Melissa C.), Spurdle, A. B. (Amanda B.), Stanford, J. L. (Janet L.), Stevens, V. L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A. J. (Anthony J.), Tajara, E. H. (Eloiza H.), Tangen, C. M. (Catherine M.), Tardon, A. (Adonina), Taylor, J. A. (Jack A.), Teare, M. D. (M. Dawn), Teixeira, M. R. (Manuel R.), Terry, M. B. (Mary Beth), Terry, K. L. (Kathryn L.), Thibodeau, S. N. (Stephen N.), Thomassen, M. (Mads), Bjorge, L. (Line), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Torres, D. (Diana), Townsend, P. A. (Paul A.), Travis, R. C. (Ruth C.), Tung, N. (Nadine), Tworoger, S. S. (Shelley S.), Ulrich, C. M. (Cornelia M.), Usmani, N. (Nawaid), Vachon, C. M. (Celine M.), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M. E. (Miguel Elias), Wang, Q. (Qin), Webb, P. M. (Penelope M.), Weinberg, C. R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M. C. (Mark C.), Weitzel, J. N. (Jeffrey N.), West, C. M. (Catharine M. L.), White, E. (Emily), Whittemore, A. S. (Alice S.), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, A. (Alicja), Woll, P. (Penella), Woods, M. (Michael), Wu, A. H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K. K. (Kristin K.), Lane, J. M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D. (Duncan), Hung, R. J. (Rayjean J.), Diergaarde, B. (Brenda), Mckay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), Garcia-Closas, M. (Montserrat), Eeles, R. A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P. J. (Paul J.), Haiman, C. A. (Christopher A.), Simard, J. (Jacques), Easton, D. F. (Douglas F.), Gruber, S. B. (Stephen B.), Pharoah, P. D. (Paul D. P.), Price, A. L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C. I. (Christopher I.), Kraft, P. (Peter), and Lindstrom, S. (Sara)
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
Published: 2019

21. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4)

Author: Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Antonenkova, N. N., Arnold, S. M., Aronson, K. J., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Batra, J., Beckmann, M. W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S. I., Bickeboller, H., Bien, S. A., Blomqvist, C., Boccia, S., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Brauch, H., Brenner, H., Brenton, J. D., Brook, M. N., Brunet, J., Brunnstrom, H., Buchanan, D. D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M. A., Campbell, I., Campbell, P. T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A. L., Chan, A. T., Chang-Claude, J., Chanock, S. J., Chen, Chen, Christiani, D. C., Claes, K. B. M., Claessens, F., Clements, J., Collee, J. M., Correa, M. C., Couch, F. J., Cox, A., Cunningham, J. M., Cybulski, C., Czene, K., Daly, M. B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J. L., Dork, T., Duell, E. J., Dunning, A. M., Dwek, M., Eccles, D. M., Edlund, C. K., Edwards, D. R. V., Ellberg, C., Evans, D. G., Fasching, P. A., Ferris, R. L., Liloglou, T., Figueiredo, J. C., Fletcher, O., Fortner, R. T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S. J., Ganz, P. A., Garber, J., Garcia-Saenz, J. A., Gayther, S. A., Giles, G. G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Goode, E. L., Goodman, M. T., Goodman, G., Grankvist, K., Greene, M. H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F. C., Hamilton, R. J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y. -C., Hopper, J. L., Houlston, R., Hulick, P. J., Hunter, D. J., Huntsman, D. G., Idos, G., Imyanitov, E. N., Ingles, S. A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M. A., Johansson, M., John, E. M., Joshi, A. D., Kaneva, R., Karlan, B. Y., Kelemen, L. E., Kuhl, T., Khaw, K. -T., Khusnutdinova, E., Kibel, A. S., Kiemeney, L. A., Kim, J., Kjaer, S. K., Knight, J. A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V. N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M. T., Lazarus, P., Le, N. D., Lee, E., Lejbkowicz, F., Lenz, H. -J., Leslie, G., Lessel, D., Lester, J., Levine, D. A., Li, L., Li, C. I., Lindblom, A., Lindor, N. M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L. L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R. L., MacInnis, R. J., Modugno, F., Montagna, M., Moreno, V., Moysich, K. B., Mucci, L., Muir, K., Mulligan, A. M., Nathanson, K. L., Neal, D. E., Ness, A. R., Neuhausen, S. L., Nevanlinna, H., Newcomb, P. A., Newcomb, L. F., Nielsen, F. C., Nikitina-Zake, L., Nordestgaard, B. G., Nussbaum, R. L., Offit, K., Olah, E., Olama, A. A. A., Olopade, O. I., Olshan, A. F., Olsson, H., Osorio, A., Pandha, H., Park, J. Y., Pashayan, N., Parsons, M. T., Pejovic, T., Penney, K. L., Peters, W. H. M., Phelan, C. M., Phipps, A. I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S. J., Raskin, L., Rennert, G., Rennert, H. S., van Rensburg, E. J., Riggan, M. J., Risch, H. A., Risch, A., Roobol, M. J., Rosenstein, B. S., Rossing, M. A., De Ruyck, K., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schabath, M. B., Schleutker, J., Schmidt, M. K., Setiawan, V. W., Shen, H., Siegel, E. M., Sieh, W., Singer, C. F., Slattery, M. L., Sorensen, K. D., Southey, M. C., Spurdle, A. B., Stanford, J. L., Stevens, V. L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A. J., Tajara, E. H., Tangen, C. M., Tardon, A., Taylor, J. A., Teare, M. D., Teixeira, M. R., Terry, M. B., Terry, K. L., Thibodeau, S. N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A. E., Torres, D., Townsend, P. A., Travis, R. C., Tung, N., Tworoger, S. S., Ulrich, C. M., Usmani, N., Vachon, C. M., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M. E., Wang, Q., Webb, P. M., Weinberg, C. R., Weinstein, S., Weissler, M. C., Weitzel, J. N., West, C. M. L., White, E., Whittemore, A. S., Wichmann, H. -E., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A. H., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K. K., Lane, J. M., Saxena, R., Thomas, D., Hung, R. J., Diergaarde, B., McKay, J., Peters, U., Hsu, L., Garcia-Closas, M., Eeles, R. A., Chenevix-Trench, G., Brennan, P. J., Haiman, C. A., Simard, J., Easton, D. F., Gruber, S. B., Pharoah, P. D. P., Price, A. L., Pasaniuc, B., Amos, C. I., Kraft, P., Lindstrom, S., Boccia S. (ORCID:0000-0002-1864-749X), Cadoni G. (ORCID:0000-0001-8244-784X), Chen C., Liu G., Wang Q., Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Antonenkova, N. N., Arnold, S. M., Aronson, K. J., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Batra, J., Beckmann, M. W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S. I., Bickeboller, H., Bien, S. A., Blomqvist, C., Boccia, S., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Brauch, H., Brenner, H., Brenton, J. D., Brook, M. N., Brunet, J., Brunnstrom, H., Buchanan, D. D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M. A., Campbell, I., Campbell, P. T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A. L., Chan, A. T., Chang-Claude, J., Chanock, S. J., Chen, Chen, Christiani, D. C., Claes, K. B. M., Claessens, F., Clements, J., Collee, J. M., Correa, M. C., Couch, F. J., Cox, A., Cunningham, J. M., Cybulski, C., Czene, K., Daly, M. B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J. L., Dork, T., Duell, E. J., Dunning, A. M., Dwek, M., Eccles, D. M., Edlund, C. K., Edwards, D. R. V., Ellberg, C., Evans, D. G., Fasching, P. A., Ferris, R. L., Liloglou, T., Figueiredo, J. C., Fletcher, O., Fortner, R. T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S. J., Ganz, P. A., Garber, J., Garcia-Saenz, J. A., Gayther, S. A., Giles, G. G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Goode, E. L., Goodman, M. T., Goodman, G., Grankvist, K., Greene, M. H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F. C., Hamilton, R. J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y. -C., Hopper, J. L., Houlston, R., Hulick, P. J., Hunter, D. J., Huntsman, D. G., Idos, G., Imyanitov, E. N., Ingles, S. A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M. A., Johansson, M., John, E. M., Joshi, A. D., Kaneva, R., Karlan, B. Y., Kelemen, L. E., Kuhl, T., Khaw, K. -T., Khusnutdinova, E., Kibel, A. S., Kiemeney, L. A., Kim, J., Kjaer, S. K., Knight, J. A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V. N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M. T., Lazarus, P., Le, N. D., Lee, E., Lejbkowicz, F., Lenz, H. -J., Leslie, G., Lessel, D., Lester, J., Levine, D. A., Li, L., Li, C. I., Lindblom, A., Lindor, N. M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L. L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R. L., MacInnis, R. J., Modugno, F., Montagna, M., Moreno, V., Moysich, K. B., Mucci, L., Muir, K., Mulligan, A. M., Nathanson, K. L., Neal, D. E., Ness, A. R., Neuhausen, S. L., Nevanlinna, H., Newcomb, P. A., Newcomb, L. F., Nielsen, F. C., Nikitina-Zake, L., Nordestgaard, B. G., Nussbaum, R. L., Offit, K., Olah, E., Olama, A. A. A., Olopade, O. I., Olshan, A. F., Olsson, H., Osorio, A., Pandha, H., Park, J. Y., Pashayan, N., Parsons, M. T., Pejovic, T., Penney, K. L., Peters, W. H. M., Phelan, C. M., Phipps, A. I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S. J., Raskin, L., Rennert, G., Rennert, H. S., van Rensburg, E. J., Riggan, M. J., Risch, H. A., Risch, A., Roobol, M. J., Rosenstein, B. S., Rossing, M. A., De Ruyck, K., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schabath, M. B., Schleutker, J., Schmidt, M. K., Setiawan, V. W., Shen, H., Siegel, E. M., Sieh, W., Singer, C. F., Slattery, M. L., Sorensen, K. D., Southey, M. C., Spurdle, A. B., Stanford, J. L., Stevens, V. L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A. J., Tajara, E. H., Tangen, C. M., Tardon, A., Taylor, J. A., Teare, M. D., Teixeira, M. R., Terry, M. B., Terry, K. L., Thibodeau, S. N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A. E., Torres, D., Townsend, P. A., Travis, R. C., Tung, N., Tworoger, S. S., Ulrich, C. M., Usmani, N., Vachon, C. M., Van Nieuwenhuysen, E., Vega, A., Aguado-Barrera, M. E., Wang, Q., Webb, P. M., Weinberg, C. R., Weinstein, S., Weissler, M. C., Weitzel, J. N., West, C. M. L., White, E., Whittemore, A. S., Wichmann, H. -E., Wiklund, F., Winqvist, R., Wolk, A., Woll, P., Woods, M., Wu, A. H., Wu, X., Yannoukakos, D., Zheng, W., Zienolddiny, S., Ziogas, A., Zorn, K. K., Lane, J. M., Saxena, R., Thomas, D., Hung, R. J., Diergaarde, B., McKay, J., Peters, U., Hsu, L., Garcia-Closas, M., Eeles, R. A., Chenevix-Trench, G., Brennan, P. J., Haiman, C. A., Simard, J., Easton, D. F., Gruber, S. B., Pharoah, P. D. P., Price, A. L., Pasaniuc, B., Amos, C. I., Kraft, P., Lindstrom, S., Boccia S. (ORCID:0000-0002-1864-749X), Cadoni G. (ORCID:0000-0001-8244-784X), Chen C., Liu G., and Wang Q.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019

22. Efficacy of salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer: a systematic review

Author: Darelius, A, primary, Lycke, M, additional, Kindblom, JM, additional, Kristjansdottir, B, additional, Sundfeldt, K, additional, and Strandell, A, additional
Published: 2017
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23. High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

Author: Österberg, L., primary, Levan, K., additional, Partheen, K., additional, Staaf, J., additional, Sundfeldt, K., additional, and Horvath, G., additional
Published: 2009
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24. Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Author: Rask, K, primary, Nilsson, A, additional, Brännström, M, additional, Carlsson, P, additional, Hellberg, P, additional, Janson, P-O, additional, Hedin, L, additional, and Sundfeldt, K, additional
Published: 2003
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25. E-cadherin-catenin complex in the rat ovary: cell-specific expression during folliculogenesis and luteal formation

Author: Sundfeldt, K, primary, Piontkewitz, Y, additional, Billig, H, additional, and Hedin, L, additional
Published: 2000
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26. The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

Author: Sundfeldt, K, primary, Ivarsson, K, additional, Carlsson, M, additional, Enerbäck, S, additional, Janson, P O, additional, Brännström, M, additional, and Hedin, L, additional
Published: 1999
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27. The expression of c-myc during follicular growth and luteal formation in the rat ovary in vivo

Author: Piontkewitz, Y, primary, Sundfeldt, K, additional, and Hedin, L, additional
Published: 1997
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28. Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta.

Author: Rask, K., Nilsson, A., Brännström, M., Carlsson, P., Hellberg, P., Janson, P.-O., Hedin, L., Sundfeldt, K., and Brännström, M
Subjects: OVARIAN tumors, EPITHELIAL tumors, IMMUNOHISTOCHEMISTRY, PROTEIN metabolism, ADENOCARCINOMA, ADENOMA, COLON tumors, COMPARATIVE studies, CYTOSKELETAL proteins, EPITHELIAL cell tumors, RESEARCH methodology, MEDICAL cooperation, PROTEINS, RECTUM tumors, RESEARCH, TRANSCRIPTION factors, TRANSFERASES, TUMORS, DNA-binding proteins, EVALUATION research, CASE-control method, CANCER cell culture, PRECIPITIN tests
Abstract: Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis. [ABSTRACT FROM AUTHOR]
Published: 2003
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29. Diverse effects of FSH and LH on proliferation of human ovarian surface epithelial cells.

Author: Ivarsson, Karin, Sundfeldt, Karin, Brännström, Mats, Hellberg, Pär, Janson, Par Olof, Ivarsson, K, Sundfeldt, K, Brännström, M, Hellberg, P, and Janson, P O
Abstract: The purpose of this study was to evaluate the effects of FSH and LH on growth regulation of normal ovarian surface epithelial (OSE) cells harvested from both premenopausal and postmenopausal women. Ovarian surface epithelial cells were obtained through brushing of the ovarian surface during surgery. FSH and LH were added to the OSE cultures and the proliferative effects were analysed using two different culture models, non-confluent and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric cell number assay. FSH lowered the OSE proliferation under non-confluent conditions (10-27%), and the inhibitory effect was most pronounced among cells from postmenopausal women (P: < 0.01). In the confluent model only cells from postmenopausal women showed significantly (P: < 0.05) decreased proliferation. No effects of LH on OSE cells were detected. The unexpected results of an anti-proliferative effect of FSH on OSE, and the absence of effect by LH, do not support the theory that gonadotrophins are directly involved in ovarian carcinogenesis through an enhanced proliferation of OSE cells. [ABSTRACT FROM AUTHOR]
Published: 2001
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30. Specific copy number alterations associated with docetaxel/carboplatin response in ovarian carcinomas

Author: Osterberg L, Levan K, Partheen K, Delle U, Björn Olsson, Sundfeldt K, and Horvath G

31. External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas.

Author: Partheen K, Levan K, Osterberg L, Claesson I, Sundfeldt K, Horvath G, Partheen, Karolina, Levan, Kristina, Osterberg, Lovisa, Claesson, Ingela, Sundfeldt, Karin, and Horvath, György
Abstract: Background: The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors.Methods: We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR) and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test.Results: The gene and protein ITGB3 (Integrin beta 3) were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME.Conclusion: The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours. [ABSTRACT FROM AUTHOR]
Published: 2009
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32. MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer.

Author: Ruma SA, Vinod R, Jain S, Huhtinen K, Hynninen J, Leivo J, Pettersson K, Sundfeldt K, and Gidwani K
Subjects: Humans, Female, Carcinoma, Ovarian Epithelial blood, Carcinoma, Ovarian Epithelial diagnosis, Immunoassay methods, CA-125 Antigen blood, Middle Aged, Glycosylation, Nanoparticles chemistry, Membrane Proteins, Ovarian Neoplasms blood, Ovarian Neoplasms diagnosis, Mucin-1 blood, Biomarkers, Tumor blood, CA-19-9 Antigen blood, Polysaccharides blood, Cyst Fluid chemistry
Abstract: Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human body fluids by probing with fluorescent nanoparticles coated with lectins or antibodies to known EOC associated proteins. CA19-9 antigens were immobilized from ascites fluids, ovarian cyst fluids or serum samples using monoclonal antibody C192 followed by probing of carrier proteins using anti-MUC16, anti-MUC1 and, anti STn antibodies and seven lectins, all separately coated on nanoparticles. Compared to reference CA19-9 and CA125 immunoassays, nanoparticle aided detection using MUC16, Ma695 and STn antibodies and lectin WGA provided, both separately and combined, improved discrimination of EOC and borderline cancers from benign samples when applied to 60 cyst fluid specimens. When applied to a panel of 44 serum samples (EOC N = 24, healthy and benign samples N = 20) two assays, CA19-9 Ma695 and CA19-9 MUC1 , stood out with equally superior separations (p-values < 10 -8 ) of the two groups compared to conventional CA19-9 immunoassay (p-value 0.03).Eu +3 -NP based CA19-9 MUC16 , CA19-9 Ma695 , CA19-9 STn and CA19-9 WGA show promise for improved EOC detection when applied to ascites & cyst fluids. When applied to circulation-derived samples, the two MUC1 based assays, CA19-9 Ma695 and CA19-9 Ma552 outperformed other assay constructs. Our results call for further validation in larger EOC cohorts preferentially with early stage ovarian cancers and all major histotypes against commonly occurring benign conditions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval statement: The study was approved by the local ethics committee Regionala etikprövningsnämnden i Göteborg (Dnr 201–15) in Gothenburg and was performed in accordance with the Declaration of Helsinki and all its amendments. Patient consent statement: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s).)
Published: 2025
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33. Optimization of pre-analytical handling to maintain DNA integrity in diagnostic Papanicolaou tests.

Author: Schumacher S, Malchau Lauesgaard J, Carlsson T, Linder A, and Sundfeldt K
Abstract: Cell-free DNA of ovarian tumor origin can be detected in samples from the gynecologic tract. This study aims to evaluate how pre-analytical handling, and storage conditions affect DNA profile and integrity in Pap tests, to optimize its potential for detection of ovarian cancers (OC). Analysis of archived Pap tests from OC patients, kept at RT for 48h and stored at -80°C was complemented by in vitro experiments. Temperature-associated effects on DNA fragmentation were evaluated in samples stored at 4°C, -20°C or -80°C. Time-dependent DNA degradation at RT was evaluated in comparison to storage at 4°C (0-96h). Results were validated in prospectively collected Pap tests. The DNA integrity was assessed by fragment analysis. Accumulation of short DNA fragments was observed in archived Pap tests from OC patients. In vitro, fragments of 100-350bp increased 11.5-fold within 48h at RT compared to 1.7-fold when stored at 4°C. Consistent with the in vitro findings, prospectively collected samples showed reduced fragmentation when stored at 4°C compared to RT (p=0.007). Long-term storage at 4°C had a significant negative effect on DNA stability (p=0.013), while freezing slowed down fragmentation. This study highlights the need for optimization of pre-analytical handling for cfDNA analysis. Immediate storage at 4°C after sampling markedly reduces DNA degradation suggesting a simple way to decrease unwanted fragmentation for cfDNA analysis in Pap tests., (Copyright © 2025. Published by Elsevier Inc.)
Published: 2025
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34. Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer - implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils.

Author: Karlsson V, Stål E, Stoopendahl E, Ivarsson A, Leffler H, Lycke M, Sundqvist M, Sundfeldt K, Christenson K, and Bernson E
Subjects: Humans, Female, Middle Aged, Aged, Galectins metabolism, K562 Cells, Cell Line, Tumor, Cytotoxicity, Immunologic, Blood Proteins, Tumor Microenvironment immunology, Neutrophils immunology, Neutrophils metabolism, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Reactive Oxygen Species metabolism, Ovarian Neoplasms immunology, Ovarian Neoplasms pathology, Ovarian Neoplasms metabolism, Galectin 3 metabolism
Abstract: Introduction: Ovarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is involved in different immune processes and has been associated with poor outcome in various cancer diagnoses. Here, we investigated how Galectin-3 affects the interaction between natural killer (NK) cells and neutrophils in the tumor microenvironment of ovarian cancer., Method: Ascites from the metastatic tumor microenvironment and cyst fluid from the primary tumor site were collected from patients with high-grade serous carcinoma (HGSC) together with peripheral blood samples. Galectin-3 concentration was measured in ascites, cyst fluid and serum or plasma. Neutrophils isolated from HGSC ascites and autologous blood were analyzed to evaluate priming status and production of reactive oxygen species. In vitro co-culture assays with NK cells, neutrophils and K562 target cells (cancer cell line) were conducted to evaluate NK cell viability, degranulation and cytotoxicity., Results: High levels of Galectin-3 were observed in cyst fluid and ascites from patients with HGSC. Neutrophils present in HGSC ascites showed signs of priming; however, the priming status varied greatly among the patient samples. Galectin-3 induced production of reactive oxygen species in ascites neutrophils, but only from a fraction of the patient samples, which is in line with the heterogenous priming status of the ascites neutrophils. In co-cultures with NK cells and K562 target cells, we observed that Galectin-3-induced production of reactive oxygen species in neutrophils resulted in decreased NK cell viability and lowered anti-tumor responses., Conclusion: Taken together, our results demonstrate high levels of Galectin-3 in the tumormicroenvironment of HGSC. High levels of Galectin-3 may induce production of reactiveoxygen species in ascites neutrophils in some patients. In turn, reactive oxygen species produced by neutrophils may modulate the NK cell anti-tumor immunity. Together, this study suggests further investigation to evaluate if a Galectin-3-targeting therapy may be used in ovarian cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karlsson, Stål, Stoopendahl, Ivarsson, Leffler, Lycke, Sundqvist, Sundfeldt, Christenson and Bernson.)
Published: 2024
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35. Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Author: Saner FAM, Takahashi K, Budden T, Pandey A, Ariyaratne D, Zwimpfer TA, Meagher NS, Fereday S, Twomey L, Pishas KI, Hoang T, Bolithon A, Traficante N, Alsop K, Christie EL, Kang EY, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Alsop J, Beckmann MW, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, El-Bahrawy MA, Elishaev E, Erber R, Gayther SA, Gentry-Maharaj A, Gilks CB, Harnett PR, Harris HR, Hartmann A, Hein A, Hendley J, Hernandez BY, Jakubowska A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Kluz T, Koziak JM, Kristjansdottir B, Le ND, Lener M, Lester J, Lubiński J, Mateoiu C, Orsulic S, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Soong TR, Steed H, Sukumvanich P, Talhouk A, Taylor SE, Vierkant RA, Wang C, Widschwendter M, Wilkens LR, Winham SJ, Anglesio MS, Berchuck A, Brenton JD, Campbell I, Cook LS, Doherty JA, Fasching PA, Fortner RT, Goodman MT, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sundfeldt K, Swerdlow AJ, Goode EL, DeFazio A, Köbel M, Ramus SJ, Bowtell DDL, and Garsed DW
Subjects: Humans, Female, Prognosis, Ubiquitin-Protein Ligases genetics, Neoplasm Grading, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Middle Aged, Germ-Line Mutation, Gene Expression Regulation, Neoplastic, Aged, Biomarkers, Tumor genetics, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Ovarian Neoplasms genetics, Ovarian Neoplasms mortality, Ovarian Neoplasms immunology, Ovarian Neoplasms pathology, BRCA2 Protein genetics, BRCA2 Protein deficiency, BRCA1 Protein genetics, BRCA1 Protein deficiency, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous mortality, Cystadenocarcinoma, Serous immunology, Retinoblastoma Binding Proteins genetics
Abstract: Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC)., Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss., Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1., Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation., (©2024 The Authors; Published by the American Association for Cancer Research.)
Published: 2024
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36. Large-scale proteomics reveals precise biomarkers for detection of ovarian cancer in symptomatic women.

Author: Ivansson E, Hedlund Lindberg J, Stålberg K, Sundfeldt K, Gyllensten U, and Enroth S
Subjects: Humans, Female, Middle Aged, Keratin-19 blood, Aged, Adult, Cohort Studies, Neoplasm Staging, Ovarian Neoplasms blood, Ovarian Neoplasms diagnosis, Biomarkers, Tumor blood, Proteomics methods, WAP Four-Disulfide Core Domain Protein 2 analysis, WAP Four-Disulfide Core Domain Protein 2 metabolism
Abstract: Ovarian cancer is the 8th most common cancer among women and has a 5-year survival of only 30-50%. While the survival is close to 90% for stage I tumours it is only 20% for stage IV. Current biomarkers are not sensitive nor specific enough, and novel biomarkers are urgently needed. We used the Explore PEA technology for large-scale analysis of 2943 plasma proteins to search for new biomarkers using two independent clinical cohorts. The discovery analysis using the first cohort identified 296 proteins that had significantly different levels in malign tumours as compared to benign and for 269 (91%) of these, the association was replicated in the second cohort. Multivariate modelling, including all proteins independent of their association in the univariate analysis, identified a model for separating benign conditions from malign tumours (stage I-IV) consisting of three proteins; WFDC2, KRT19 and RBFOX3. This model achieved an AUC of 0.92 in the replication cohort and a sensitivity and specificity of 0.93 and 0.77 at a cut-off developed in the discovery cohort. There was no statistical difference of the performance in the replication cohort compared to the discovery cohort. WFDC2 and KRT19 have previously been associated with ovarian cancer but RBFOX3 has not previously been identified as a potential biomarker. Our results demonstrate the ability of using high-throughput precision proteomics for identification of novel plasma protein biomarker for ovarian cancer detection., (© 2024. The Author(s).)
Published: 2024
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37. Spatial tumor immune microenvironment phenotypes in ovarian cancer.

Author: Mateiou C, Lokhande L, Diep LH, Knulst M, Carlsson E, Ek S, Sundfeldt K, and Gerdtsson A
Abstract: Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and Fibronectin. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with diffuse infiltration and a high expression of STING, while endometrioid OC had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches., (© 2024. The Author(s).)
Published: 2024
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38. Awareness of somatisation disorder among Swedish physicians at emergency departments: a cross-sectional survey.

Author: Iloson C, Praetorius Björk M, Möller A, Sundfeldt K, and Bernhardsson S
Subjects: Humans, Male, Female, Cross-Sectional Studies, Sweden, Emergency Service, Hospital, Surveys and Questionnaires, Medicine, Physicians psychology
Abstract: Background: Somatisation is a highly prevalent psychiatric syndrome in both women and men, in which psychological distress is manifested in physical symptoms without a medical explanation. Many patients with somatisation disorder are high healthcare utilisers, particularly at emergency departments. Unnecessary investigations and diagnostic operations occur frequently, which cause both patient suffering and a significant burden on the healthcare system. Emergency department physicians' awareness of somatisation and its manifestations has not previously been studied. This study aimed to investigate awareness about somatisation disorder among physicians working at emergency departments in western Sweden, and to explore differences between gender, specialty, and work experience., Methods: A web-based, cross-sectional survey consisting of six dichotomous questions about somatisation disorder was conducted, in December 2021 - January 2022, among licensed physicians of various specialties working at emergency departments in western Sweden. Descriptive analyses and comparative analyses were performed to investigate differences between gender, type of specialty, and years of practice. Data were analysed using chi 2 tests and Fisher's exact test., Results: Of the 526 eligible physicians who received the survey, 241 responded; response rate 45.8%. The majority of the respondents (56.4%) were women, and most (35.3%) were specialised in obstetrics/gynaecology. Average years of work experience was 11.1 (SD 8.7) years. Although 71% of respondents were aware of the diagnosis, only 7% knew the diagnostic criteria and only 6% had ever diagnosed a patient with somatisation disorder. Female physicians were more aware of underlying factors than their male colleagues (55.7% vs. 38.2%; p = .010). Type of specialty or years of practice did not affect awareness., Conclusions: Awareness of somatisation disorder is low among physicians working at emergency departments in western Sweden. The findings suggest a need to increase awareness and knowledge and provide training in diagnosing the condition, to ensure correct decisions and optimal patient management. Clinical guidelines need to be developed to support diagnosis, investigation, and treatment, in Sweden as well as internationally., (© 2024. The Author(s).)
Published: 2024
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39. Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid.

Author: Hedlund Lindberg J, Widgren A, Ivansson E, Gustavsson I, Stålberg K, Gyllensten U, Sundfeldt K, Bergquist J, and Enroth S
Abstract: Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence-based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91-1.00) at a specificity of 0.67 (0.40-0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)
Published: 2024
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40. Concurrent RB1 loss and BRCA -deficiency predicts enhanced immunological response and long-term survival in tubo-ovarian high-grade serous carcinoma.

Author: Saner FAM, Takahashi K, Budden T, Pandey A, Ariyaratne D, Zwimpfer TA, Meagher NS, Fereday S, Twomey L, Pishas KI, Hoang T, Bolithon A, Traficante N, Alsop K, Christie EL, Kang EY, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Alsop J, Beckmann MW, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, El-Bahrawy MA, Elishaev E, Erber R, Gayther SA, Gentry-Maharaj A, Blake Gilks C, Harnett PR, Harris HR, Hartmann A, Hein A, Hendley J, Hernandez BY, Jakubowska A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Kluz T, Koziak JM, Kristjansdottir B, Le ND, Lener M, Lester J, Lubiński J, Mateoiu C, Orsulic S, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Singh N, Rinda Soong T, Steed H, Sukumvanich P, Talhouk A, Taylor SE, Vierkant RA, Wang C, Widschwendter M, Wilkens LR, Winham SJ, Anglesio MS, Berchuck A, Brenton JD, Campbell I, Cook LS, Doherty JA, Fasching PA, Fortner RT, Goodman MT, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sundfeldt K, Swerdlow AJ, Goode EL, DeFazio A, Köbel M, Ramus SJ, Bowtell DDL, and Garsed DW
Abstract: Background: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which frequently co-occurs with alterations in homologous recombination DNA repair genes including BRCA1 and BRCA2 ( BRCA ). We examined whether tumour expression of RB1 was associated with survival across ovarian cancer histotypes (HGSC, endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous carcinoma (LGSC)), and how co-occurrence of germline BRCA pathogenic variants and RB1 loss influences long-term survival in a large series of HGSC., Patients and Methods: RB1 protein expression patterns were classified by immunohistochemistry in epithelial ovarian carcinomas of 7436 patients from 20 studies participating in the Ovarian Tumor Tissue Analysis consortium and assessed for associations with overall survival (OS), accounting for patient age at diagnosis and FIGO stage. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to survival, tumour infiltrating CD8+ lymphocyte counts and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cell lines with and without BRCA1 mutations to model co-loss with treatment response. We also performed genomic analyses on 126 primary HGSC to explore the molecular characteristics of concurrent homologous recombination deficiency and RB1 loss., Results: RB1 protein loss was most frequent in HGSC (16.4%) and was highly correlated with RB1 mRNA expression. RB1 loss was associated with longer OS in HGSC (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.66-0.83, P = 6.8 ×10 -7 ), but with poorer prognosis in ENOC (HR 2.17, 95% CI 1.17-4.03, P = 0.0140). Germline BRCA mutations and RB1 loss co-occurred in HGSC ( P < 0.0001). Patients with both RB1 loss and germline BRCA mutations had a superior OS (HR 0.38, 95% CI 0.25-0.58, P = 5.2 ×10 -6 ) compared to patients with either alteration alone, and their median OS was three times longer than non-carriers whose tumours retained RB1 expression (9.3 years vs. 3.1 years). Enhanced sensitivity to cisplatin ( P < 0.01) and paclitaxel ( P < 0.05) was seen in BRCA1 mutated cell lines with RB1 knockout. Among 126 patients with whole-genome and transcriptome sequence data, combined RB1 loss and genomic evidence of homologous recombination deficiency was correlated with transcriptional markers of enhanced interferon response, cell cycle deregulation, and reduced epithelial-mesenchymal transition in primary HGSC. CD8+ lymphocytes were most prevalent in BRCA -deficient HGSC with co-loss of RB1 ., Conclusions: Co-occurrence of RB1 loss and BRCA mutation was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation., Competing Interests: COMPETING INTERESTS DDLB is an Exo Therapeutics advisor and has received research grant funding from AstraZeneca, Genentech-Roche and BeiGene for unrelated work. SF, NT, KA, and ADeF received grant funding from AstraZeneca for unrelated work. AGM and UM report funded research collaborations for unrelated work with industry: Intelligent Lab on Fiber, RNA Guardian, Micronoma and Mercy BioAnalytics. UM had stock ownership (2011–2021) awarded by University College London (UCL) in Abcodia, which held the licence for the Risk of Ovarian Cancer Algorithm (ROCA). UM reports research collaboration contracts with Cambridge University and QIMR Berghofer Medical Research Institute. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. UM is a member of Tina’s Wish Scientific Advisory Board (USA) and Research Advisory Panel, Yorkshire Cancer Research (UK). The remaining authors declared no conflicts of interest.
Published: 2023
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41. SALpingectomy for STERilisation (SALSTER): study protocol for a Swedish multicentre register-based randomised controlled trial.

Author: Magarakis L, Idahl A, Sundfeldt K, Liv P, Pålsson M, and Strandell A
Subjects: Female, Humans, Pregnancy, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Salpingectomy, Sterilization, Sweden, Adult, Cesarean Section, Ovarian Neoplasms prevention & control, Ovarian Neoplasms surgery
Abstract: Introduction: Salpingectomy is currently suggested as an alternative to tubal ligation for sterilisation. Precursor lesions of ovarian carcinoma can be found in the fallopian tubes; thus, salpingectomy could possibly reduce the incidence. Most of the existing trials on safety are small, on caesarean section and report on surrogate ovarian function measures. Randomised trials in laparoscopy are lacking. Well-designed trials are needed to evaluate safety of laparoscopic opportunistic salpingectomy., Methods and Analysis: In SALSTER, a national register-based randomised controlled non-inferiority trial, 968 women <50 years, wishing laparoscopic sterilisation will be randomised to either salpingectomy or tubal ligation. The Swedish National Quality Register of Gynecological Surgery (GynOp) will be used for inclusion, randomisation and follow-up. Primary outcomes are any complication up to 8 weeks postoperatively, and age at menopause . Both outcomes are measured with questionnaires, complications are also assessed by a gynaecologist. In a nested trial, ovarian function will be evaluated comparing the mean difference of anti-Müllerian hormone (AMH), assessed preoperatively and 1 year after surgery., Ethics and Dissemination: Performing salpingectomy for sterilisation has become increasingly common, despite the unclear risk-benefit balance. SALSTER studies the safety of salpingectomy compared with tubal ligation. Regardless of the result, SALSTER will provide gynaecologists with high quality evidence to inform women to decide on salpingectomy or not. The central ethical review board of Gothenburg, Sweden (Dnr. 316-18) approved the trial in 2018. Results will be presented at scientific congresses and published in peer-reviewed scientific journals. The results will be communicated through professional organisations and research networks., Trial Registration Number: NCT03860805., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2023
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42. Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients.

Author: Bernson E, Huhn O, Karlsson V, Hawkes D, Lycke M, Cazzetta V, Mikulak J, Hall J, Piskorz AM, Portuesi R, Vitobello D, Fiamengo B, Siesto G, Horowitz A, Ghadially H, Mavilio D, Brenton JD, Sundfeldt K, and Colucci F
Abstract: Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8 + T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency. Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8 + T cells were detected in the peritoneal fluid upon tumor growth. Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
Published: 2023
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43. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

Author: Köbel M, Kang EY, Weir A, Rambau PF, Lee CH, Nelson GS, Ghatage P, Meagher NS, Riggan MJ, Alsop J, Anglesio MS, Beckmann MW, Bisinotto C, Boisen M, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, Deen S, El-Bahrawy MA, Elishaev E, Erber R, Fereday S, Fischer A, Gayther SA, Barquin-Garcia A, Gentry-Maharaj A, Gilks CB, Gronwald H, Grube M, Harnett PR, Harris HR, Hartkopf AD, Hartmann A, Hein A, Hendley J, Hernandez BY, Huang Y, Jakubowska A, Jimenez-Linan M, Jones ME, Kennedy CJ, Kluz T, Koziak JM, Lesnock J, Lester J, Lubiński J, Longacre TA, Lycke M, Mateoiu C, McCauley BM, McGuire V, Ney B, Olawaiye A, Orsulic S, Osorio A, Paz-Ares L, Ramón Y Cajal T, Rothstein JH, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Singh N, Steed H, Storr SJ, Talhouk A, Traficante N, Wang C, Whittemore AS, Widschwendter M, Wilkens LR, Winham SJ, Benitez J, Berchuck A, Bowtell DD, Candido Dos Reis FJ, Campbell I, Cook LS, DeFazio A, Doherty JA, Fasching PA, Fortner RT, García MJ, Goodman MT, Goode EL, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Kommoss S, Le ND, Martin SG, Menon U, Modugno F, Pharoah PD, Schildkraut JM, Sieh W, Staebler A, Sundfeldt K, Swerdlow AJ, Ramus SJ, and Brenton JD
Subjects: Humans, Female, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Carcinoma, Ovarian Epithelial, Ovarian Neoplasms pathology, Carcinoma, Endometrioid metabolism
Abstract: Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)
Published: 2023
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44. HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial.

Author: Idahl A, Liv P, Darelius A, Collins E, Sundfeldt K, Pålsson M, and Strandell A
Subjects: Female, Humans, Carcinoma, Ovarian Epithelial surgery, Salpingectomy adverse effects, Salpingectomy methods, Registries, Treatment Outcome, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Hysterectomy adverse effects, Hysterectomy methods, Ovarian Neoplasms surgery
Abstract: Background: The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3083-8 . Here, we report amendments made to the study protocol since commencement of the trial., Changes in Methods and Analysis: The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis. The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome. Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms., Discussion: The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached., Trial Registration: ClinicalTrials.gov, NCT03045965 . Registered 8 February 2017., (© 2023. The Author(s).)
Published: 2023
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45. Aberrant glycosylation of α3 integrins as diagnostic markers in epithelial ovarian cancer.

Author: Jain S, Parimelazhagan Santhi P, Vinod R, Afrin Ruma S, Huhtinen K, Pettersson K, Sundfeldt K, Leivo J, and Gidwani K
Subjects: Female, Humans, Biomarkers, Tumor metabolism, Carcinoma, Ovarian Epithelial diagnosis, Europium, Glycosylation, Integrins metabolism, Integrin alpha3 metabolism, Metal Nanoparticles, Ovarian Cysts, Ovarian Neoplasms diagnosis, Ovarian Neoplasms metabolism
Abstract: Background: Glycans are strongly involved in stability and function of integrins (ITG) and tetraspanin protein CD63 and their respective interaction partners as they are dysregulated in the tumorigenic processes. Glycosylation changes is a universal phenomenon of cancer cells. In this study, glycosylation changes in epithelial ovarian cancer (EOC) are explored using tetraspanin and integrin molecules., Methods: ITG and CD63 were immobilized from 10 EOC and 5 benign ovarian cyst fluid on microtiter wells and traced with 3 glycan binding proteins (STn, WGA, UEA) conjugated on europium nanoparticles. Total protein measurements (ITG & CD63 immunoassays) were also performed. The most promising glycovariant candidates identified were then clinically evaluated on the whole cohort of 77 ovarian cyst fluids. Additional testing was performed in ascites fluid samples of liver cirrhosis (n = 2) and EOC (n = 4)., Results: Sialylated Tn antibody based glycovariants of ITGα3 (ITGα3 STn ) and CD63 (CD63 STn ) performed better than corresponding protein epitope-based immunoassays, ITGα3 IA and CD63 IA respectively. Combined ITGα3 based assays (ITGα3 IA + ITGα3 STn ) detected 49 out of 55 malignant & borderline cases without detecting any of the 22 benign and healthy cysts., Conclusion: Our findings indicate the potential diagnostic application of ITGα3 STn along with total ITGα3 IA , which could help reduce the unnecessary surgeries. The results encourage studying further the potential use of these novel assays to detect EOC at earlier clinical stages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2023
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46. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

Author: Kang EY, Weir A, Meagher NS, Farrington K, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Bolithon A, Popovic G, Leung B, Tang K, Lambie N, Millstein J, Alsop J, Anglesio MS, Ataseven B, Barlow E, Beckmann MW, Berger J, Bisinotto C, Bösmüller H, Boros J, Brand AH, Brooks-Wilson A, Brucker SY, Carney ME, Casablanca Y, Cazorla-Jiménez A, Cohen PA, Conrads TP, Cook LS, Coulson P, Courtney-Brooks M, Cramer DW, Crowe P, Cunningham JM, Cybulski C, Darcy KM, El-Bahrawy MA, Elishaev E, Erber R, Farrell R, Fereday S, Fischer A, García MJ, Gayther SA, Gentry-Maharaj A, Gilks CB, Grube M, Harnett PR, Harrington SP, Harter P, Hartmann A, Hecht JL, Heikaus S, Hein A, Heitz F, Hendley J, Hernandez BY, Polo SH, Heublein S, Hirasawa A, Høgdall E, Høgdall CK, Horlings HM, Huntsman DG, Huzarski T, Jewell A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Khabele D, Kommoss FKF, Kruitwagen RFPM, Lambrechts D, Le ND, Lener M, Lester J, Leung Y, Linder A, Loverix L, Lubiński J, Madan R, Maxwell GL, Modugno F, Neuhausen SL, Olawaiye A, Olbrecht S, Orsulic S, Palacios J, Pearce CL, Pike MC, Quinn CM, Mohan GR, Rodríguez-Antona C, Ruebner M, Ryan A, Salfinger SG, Sasamoto N, Schildkraut JM, Schoemaker MJ, Shah M, Sharma R, Shvetsov YB, Singh N, Sonke GS, Steele L, Stewart CJR, Sundfeldt K, Swerdlow AJ, Talhouk A, Tan A, Taylor SE, Terry KL, Tołoczko A, Traficante N, Van de Vijver KK, van der Aa MA, Van Gorp T, Van Nieuwenhuysen E, van-Wagensveld L, Vergote I, Vierkant RA, Wang C, Wilkens LR, Winham SJ, Wu AH, Benitez J, Berchuck A, Candido Dos Reis FJ, DeFazio A, Fasching PA, Goode EL, Goodman MT, Gronwald J, Karlan BY, Kommoss S, Menon U, Sinn HP, Staebler A, Brenton JD, Bowtell DD, Pharoah PDP, Ramus SJ, and Köbel M
Subjects: Female, Humans, Transcription Factors genetics, RNA, Messenger, Oncogene Proteins genetics, Oncogene Proteins therapeutic use, Cyclin E genetics, Ovarian Neoplasms pathology, Carcinoma, Cystadenocarcinoma, Serous genetics
Abstract: Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC., Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated., Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss., Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
Published: 2023
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47. Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.

Author: Meagher NS, Gorringe KL, Wakefield M, Bolithon A, Pang CNI, Chiu DS, Anglesio MS, Mallitt KA, Doherty JA, Harris HR, Schildkraut JM, Berchuck A, Cushing-Haugen KL, Chezar K, Chou A, Tan A, Alsop J, Barlow E, Beckmann MW, Boros J, Bowtell DDL, Brand AH, Brenton JD, Campbell I, Cheasley D, Cohen J, Cybulski C, Elishaev E, Erber R, Farrell R, Fischer A, Fu Z, Gilks B, Gill AJ, Gourley C, Grube M, Harnett PR, Hartmann A, Hettiaratchi A, Høgdall CK, Huzarski T, Jakubowska A, Jimenez-Linan M, Kennedy CJ, Kim BG, Kim JW, Kim JH, Klett K, Koziak JM, Lai T, Laslavic A, Lester J, Leung Y, Li N, Liauw W, Lim BWX, Linder A, Lubiński J, Mahale S, Mateoiu C, McInerny S, Menkiszak J, Minoo P, Mittelstadt S, Morris D, Orsulic S, Park SY, Pearce CL, Pearson JV, Pike MC, Quinn CM, Mohan GR, Rao J, Riggan MJ, Ruebner M, Salfinger S, Scott CL, Shah M, Steed H, Stewart CJR, Subramanian D, Sung S, Tang K, Timpson P, Ward RL, Wiedenhoefer R, Thorne H, Cohen PA, Crowe P, Fasching PA, Gronwald J, Hawkins NJ, Høgdall E, Huntsman DG, James PA, Karlan BY, Kelemen LE, Kommoss S, Konecny GE, Modugno F, Park SK, Staebler A, Sundfeldt K, Wu AH, Talhouk A, Pharoah PDP, Anderson L, DeFazio A, Köbel M, Friedlander ML, and Ramus SJ
Subjects: Female, Humans, Neoplasm Staging, Carcinoma, Ovarian Epithelial pathology, Prognosis, Ovarian Neoplasms metabolism, Adenocarcinoma, Mucinous genetics, Adenocarcinoma, Mucinous diagnosis, Gastrointestinal Neoplasms metabolism
Abstract: Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features., Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55)., Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%)., Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies., (©2022 The Authors; Published by the American Association for Cancer Research.)
Published: 2022
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48. Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma.

Author: de Melo ALL, Linder A, Sundfeldt K, Lindquist D, and Hedman H
Subjects: Female, Humans, Prognosis, Carcinoma, Membrane Glycoproteins blood, Ovarian Neoplasms diagnosis
Abstract: Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously., Materials and Methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses., Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma., Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.
Published: 2022
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49. Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment.

Author: Enroth S, Ivansson E, Lindberg JH, Lycke M, Bergman J, Reneland A, Stålberg K, Sundfeldt K, and Gyllensten U
Abstract: Background: Ovarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30-50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass., Methods: Protein concentrations of 11 proteins were characterized in plasma from 1120 clinical samples with a custom version of the proximity extension assay. The performance of the assay was evaluated in terms of prediction accuracy based on receiver operating characteristics (ROC) and multiple hypothesis adjusted Fisher's Exact tests on achieved sensitivity and specificity., Results: The assay's performance is validated in two independent clinical cohorts with a sensitivity of 0.83/0.91 and specificity of 0.88/0.92. We also show that the risk score follows the clinical development and is reduced upon treatment, and increased with relapse and cancer progression. Data-driven modeling of the risk score patterns during a 2-year follow-up after diagnosis identifies four separate risk score trajectories linked to clinical development and survival. A Cox proportional hazard regression analysis of 5-year survival shows that at time of diagnosis the risk score is the second-strongest predictive variable for survival after tumor stage, whereas MUCIN-16 (CA-125) alone is not significantly predictive., Conclusion: The robust performance of the biomarker assay across clinical cohorts and the correlation with clinical development indicates its usefulness both in the diagnostic work-up of women with adnexal ovarian mass and for predicting their clinical course., Competing Interests: Competing interestsS.E., K.Su., and U.G. are inventors on a patent application entitled “Biomarker panel for ovarian cancer” (2018, US20210255189A1, pending). J.B. and A.R. are employees of Olink Proteomics AB, Uppsala, Sweden. The remaining authors declare no competing interests., (© The Author(s) 2022.)
Published: 2022
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50. Diagnostic potential of nanoparticle aided assays for MUC16 and MUC1 glycovariants in ovarian cancer.

Author: Jain S, Nadeem N, Ulfenborg B, Mäkelä M, Ruma SA, Terävä J, Huhtinen K, Leivo J, Kristjansdottir B, Pettersson K, Sundfeldt K, and Gidwani K
Subjects: Biomarkers, Tumor, CA-125 Antigen, Carcinoma, Ovarian Epithelial diagnosis, Female, Humans, Membrane Proteins, Mucin-1, Mucins, Nanoparticles, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology
Abstract: Our study reports the discovery and evaluation of nanoparticle aided sensitive assays for glycovariants of MUC16 and MUC1 in a unique collection of paired ovarian cyst fluids and serum samples obtained at or prior to surgery for ovarian carcinoma suspicion. Selected glycovariants and the immunoassays for CA125, CA15-3 and HE4 were compared and validated in 347 cyst fluid and serum samples. Whereas CA125 and CA15-3 performed poorly in cyst fluid to separate carcinoma and controls, four glycovariants including MUC16 MGL , MUC16 STn , MUC1 STn and MUC1 Tn provided highly improved separations. In serum, the two STn glycovariants outperformed conventional CA125, CA15-3 and HE4 assays in all subcategories analyzed with main benefits obtained at high specificities and at postmenopausal and early-stage disease. Serum MUC16 STn performed best at high specificity (90%-99%), but sensitivity was also improved by the other glycovariants and CA15-3. The highly improved specificity, excellent analytical sensitivity and robustness of the nanoparticle assisted glycovariant assays carry great promise for improved identification and early detection of ovarian carcinoma in routine differential diagnostics., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Published: 2022
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