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Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
- Source :
- Cancer Epidemiology, Biomarkers & Prevention, 30, 1, pp. 217-228, Cancer Epidemiology, Biomarkers & Prevention, 30, 217-228, Cancer epidemiology, biomarkers & prevention, 30(1), 217-228. American Association for Cancer Research Inc., Glubb, D M, Thompson, D J, Aben, K K, Alsulimani, A, Amant, F, Annibali, D, Attia, J, Barricarte, A, Beckmann, M W, Berchuck, A, Bermisheva, M, Bernardini, M Q, Bischof, K, Bjørge, L, Bodelon, C, Brand, A H, Brenton, J D, Brinton, L A, Bruinsma, F, Buchanan, D D, Burghaus, S, Bützow, R, Cai, H, Carney, M E, Chanock, S J, Chen, C, Chen, X, Chen, Z, Cook, L S, Cunningham, J M, De Vivo, I, Defazio, A, Doherty, J A, Dork, T, Du Bois, A, Dunning, A M, Durst, M, Edwards, T, Edwards, R P, Ekici, A B, Ewing, A, Fasching, P A, Ferguson, S, Flanagan, J M, Fostira, F, Fountzilas, G, Friedenreich, C M, Gao, B, Gaudet, M M, Gawełko, J, Gentry-maharaj, A, Giles, G G, Glasspool, R, Goodman, M T, Gronwald, J, Harris, H R, Harter, P, Hein, A, Heitz, F, Hildebrandt, M A T, Hillemanns, P, Høgdall, E, Høgdall, C K, Holliday, E G, Huntsman, D G, Huzarski, T, Jakubowska, A, Jensen, A, Jones, M E, Karlan, B Y, Karnezis, A, Kelley, J L, Khusnutdinova, E, Killeen, J L, Kjaer, S K, Klapdor, R, Köbel, M, Konopka, B, Konstantopoulou, I, Kopperud, R K, Koti, M, Kraft, P, Kupryjanczyk, J, Lambrechts, D, Larson, M C, Le Marchand, L, Lele, S, Lester, J, Li, A J, Liang, D, Liebrich, C, Lipworth, L, Lissowska, J, Lu, L, Lu, K H, Macciotta, A, Mattiello, A, May, T, Mcalpine, J N, Mcguire, V, Mcneish, I A, Menon, U, Modugno, F, Moysich, K B, Nevanlinna, H, Odunsi, K, Olsson, H, Orsulic, S, Osorio, A, Palli, D, Park-simon, T, Pearce, C L, Pejovic, T, Permuth, J B, Podgorska, A, Ramus, S J, Rebbeck, T R, Riggan, M J, Risch, H A, Rothstein, J H, Runnebaum, I B, Scott, R J, Sellers, T A, Senz, J, Setiawan, V W, Siddiqui, N, Sieh, W, Spiewankiewicz, B, Sutphen, R, Swerdlow, A J, Szafron, L M, Teo, S H, Thompson, P J, Thomsen, L C V, Titus, L, Tone, A, Tumino, R, Turman, C, Vanderstichele, A, Velez Edwards, D, Vergote, I, Vierkant, R A, Wang, Z, Wang-gohrke, S, Webb, P M, White, E, Whittemore, A S, Winham, S J, Wu, X, Wu, A H, Yannoukakos, D, Spurdle, A B & O'mara, T A 2021, ' Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers. ', Cancer Epidemiology, Biomarkers & Prevention, vol. 30, no. 1, cebp.0739.2020, pp. 217-228 . https://doi.org/10.1158/1055-9965.EPI-20-0739
- Publication Year :
- 2021
-
Abstract
- Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Epidemiology
Quantitative Trait Loci
Genome-wide association study
Biology
Carcinoma, Ovarian Epithelial
Genetic correlation
03 medical and health sciences
0302 clinical medicine
All institutes and research themes of the Radboud University Medical Center
Uterine cancer
Risk Factors
Internal medicine
medicine
Humans
Genetic association
Ovarian Neoplasms
Endometrial cancer
Cancer
medicine.disease
3. Good health
Endometrial Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
Human genome
Female
Ovarian cancer
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 10559965
- Database :
- OpenAIRE
- Journal :
- Cancer Epidemiology, Biomarkers & Prevention, 30, 1, pp. 217-228, Cancer Epidemiology, Biomarkers & Prevention, 30, 217-228, Cancer epidemiology, biomarkers & prevention, 30(1), 217-228. American Association for Cancer Research Inc., Glubb, D M, Thompson, D J, Aben, K K, Alsulimani, A, Amant, F, Annibali, D, Attia, J, Barricarte, A, Beckmann, M W, Berchuck, A, Bermisheva, M, Bernardini, M Q, Bischof, K, Bjørge, L, Bodelon, C, Brand, A H, Brenton, J D, Brinton, L A, Bruinsma, F, Buchanan, D D, Burghaus, S, Bützow, R, Cai, H, Carney, M E, Chanock, S J, Chen, C, Chen, X, Chen, Z, Cook, L S, Cunningham, J M, De Vivo, I, Defazio, A, Doherty, J A, Dork, T, Du Bois, A, Dunning, A M, Durst, M, Edwards, T, Edwards, R P, Ekici, A B, Ewing, A, Fasching, P A, Ferguson, S, Flanagan, J M, Fostira, F, Fountzilas, G, Friedenreich, C M, Gao, B, Gaudet, M M, Gawełko, J, Gentry-maharaj, A, Giles, G G, Glasspool, R, Goodman, M T, Gronwald, J, Harris, H R, Harter, P, Hein, A, Heitz, F, Hildebrandt, M A T, Hillemanns, P, Høgdall, E, Høgdall, C K, Holliday, E G, Huntsman, D G, Huzarski, T, Jakubowska, A, Jensen, A, Jones, M E, Karlan, B Y, Karnezis, A, Kelley, J L, Khusnutdinova, E, Killeen, J L, Kjaer, S K, Klapdor, R, Köbel, M, Konopka, B, Konstantopoulou, I, Kopperud, R K, Koti, M, Kraft, P, Kupryjanczyk, J, Lambrechts, D, Larson, M C, Le Marchand, L, Lele, S, Lester, J, Li, A J, Liang, D, Liebrich, C, Lipworth, L, Lissowska, J, Lu, L, Lu, K H, Macciotta, A, Mattiello, A, May, T, Mcalpine, J N, Mcguire, V, Mcneish, I A, Menon, U, Modugno, F, Moysich, K B, Nevanlinna, H, Odunsi, K, Olsson, H, Orsulic, S, Osorio, A, Palli, D, Park-simon, T, Pearce, C L, Pejovic, T, Permuth, J B, Podgorska, A, Ramus, S J, Rebbeck, T R, Riggan, M J, Risch, H A, Rothstein, J H, Runnebaum, I B, Scott, R J, Sellers, T A, Senz, J, Setiawan, V W, Siddiqui, N, Sieh, W, Spiewankiewicz, B, Sutphen, R, Swerdlow, A J, Szafron, L M, Teo, S H, Thompson, P J, Thomsen, L C V, Titus, L, Tone, A, Tumino, R, Turman, C, Vanderstichele, A, Velez Edwards, D, Vergote, I, Vierkant, R A, Wang, Z, Wang-gohrke, S, Webb, P M, White, E, Whittemore, A S, Winham, S J, Wu, X, Wu, A H, Yannoukakos, D, Spurdle, A B & O'mara, T A 2021, ' Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers. ', Cancer Epidemiology, Biomarkers & Prevention, vol. 30, no. 1, cebp.0739.2020, pp. 217-228 . https://doi.org/10.1158/1055-9965.EPI-20-0739
- Accession number :
- edsair.doi.dedup.....05013621ea6b2cd03a98c84750051500
- Full Text :
- https://doi.org/10.1158/1055-9965.EPI-20-0739