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51. Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort

Author

Sarink, Danja, primary, Schock, Helena, additional, Johnson, Theron, additional, Overvad, Kim, additional, Holm, Marianne, additional, Tjønneland, Anne, additional, Boutron-Ruault, Marie-Christine, additional, His, Mathilde, additional, Kvaskoff, Marina, additional, Boeing, Heiner, additional, Lagiou, Pagona, additional, Papatesta, Eleni-Maria, additional, Trichopoulou, Antonia, additional, Palli, Domenico, additional, Pala, Valeria, additional, Mattiello, Amalia, additional, Tumino, Rosario, additional, Sacerdote, Carlotta, additional, Bueno-de-Mesquita, H.B(as)., additional, van Gils, Carla H., additional, Peeters, Petra H., additional, Weiderpass, Elisabete, additional, Agudo, Antonio, additional, Sánchez, Maria-José, additional, Chirlaque, Maria-Dolores, additional, Ardanaz, Eva, additional, Amiano, Pilar, additional, Khaw, Kay Tee, additional, Travis, Ruth, additional, Dossus, Laure, additional, Gunter, Mark, additional, Rinaldi, Sabina, additional, Merritt, Melissa, additional, Riboli, Elio, additional, Kaaks, Rudolf, additional, and Fortner, Renée T., additional

Published
2017
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52. Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case–control study in the Northern Sweden Maternity Cohort

Author

Fortner, Renée T., primary, Tolockiene, Eglé, additional, Schock, Helena, additional, Oda, Husam, additional, Lakso, Hans-Åke, additional, Hallmans, Göran, additional, Kaaks, Rudolf, additional, Toniolo, Paolo, additional, Zeleniuch-Jacquotte, Anne, additional, Grankvist, Kjell, additional, and Lundin, Eva, additional

Published
2017
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53. Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium

Author

Ose, Jennifer, primary, Poole, Elizabeth M., additional, Schock, Helena, additional, Lehtinen, Matti, additional, Arslan, Alan A., additional, Zeleniuch-Jacquotte, Anne, additional, Visvanathan, Kala, additional, Helzlsouer, Kathy, additional, Buring, Julie E., additional, Lee, I-Min, additional, Tjønneland, Anne, additional, Dossus, Laure, additional, Trichopoulou, Antonia, additional, Masala, Giovanna, additional, Onland-Moret, N. Charlotte, additional, Weiderpass, Elisabete, additional, Duell, Eric J., additional, Idahl, Annika, additional, Travis, Ruth C., additional, Rinaldi, Sabina, additional, Merritt, Melissa A., additional, Trabert, Britton, additional, Wentzensen, Nicolas, additional, Tworoger, Shelley S., additional, Kaaks, Rudolf, additional, and Fortner, Renée T., additional

Published
2017
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55. Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort

Author

Fortner, Renée T., primary, Vitonis, Allison F., additional, Schock, Helena, additional, Hüsing, Anika, additional, Johnson, Theron, additional, Fichorova, Raina N., additional, Fashemi, Titilayo, additional, Yamamoto, Hidemi S., additional, Tjønneland, Anne, additional, Hansen, Louise, additional, Overvad, Kim, additional, Boutron-Ruault, Marie-Christine, additional, Kvaskoff, Marina, additional, Severi, Gianluca, additional, Boeing, Heiner, additional, Trichopoulou, Antonia, additional, Benetou, Vassiliki, additional, La Vecchia, Carlo, additional, Palli, Domenico, additional, Sieri, Sabina, additional, Tumino, Rosario, additional, Matullo, Giuseppe, additional, Mattiello, Amalia, additional, Onland-Moret, N. Charlotte, additional, Peeters, Petra H., additional, Weiderpass, Elisabete, additional, Gram, Inger Torhild, additional, Jareid, Mie, additional, Quirós, J. Ramón, additional, Duell, Eric J., additional, Sánchez, Maria-Jose, additional, Chirlaque, María Dolores, additional, Ardanaz, Eva, additional, Larrañaga, Nerea, additional, Nodin, Björn, additional, Brändstedt, Jenny, additional, Idahl, Annika, additional, Khaw, Kay-Tee, additional, Allen, Naomi, additional, Gunter, Marc, additional, Johansson, Mattias, additional, Dossus, Laure, additional, Merritt, Melissa A., additional, Riboli, Elio, additional, Cramer, Daniel W., additional, Kaaks, Rudolf, additional, and Terry, Kathryn L., additional

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2017
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56. Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort

Author

Fortner, Renée T., primary, Sarink, Danja, additional, Schock, Helena, additional, Johnson, Theron, additional, Tjønneland, Anne, additional, Olsen, Anja, additional, Overvad, Kim, additional, Affret, Aurélie, additional, His, Mathilde, additional, Boutron-Ruault, Marie-Christine, additional, Boeing, Heiner, additional, Trichopoulou, Antonia, additional, Naska, Androniki, additional, Orfanos, Philippos, additional, Palli, Domenico, additional, Sieri, Sabina, additional, Mattiello, Amalia, additional, Tumino, Rosario, additional, Ricceri, Fulvio, additional, Bueno-de-Mesquita, H. Bas, additional, Peeters, Petra H. M., additional, Van Gils, Carla H., additional, Weiderpass, Elisabete, additional, Lund, Eiliv, additional, Quirós, J. Ramón, additional, Agudo, Antonio, additional, Sánchez, Maria-José, additional, Chirlaque, María-Dolores, additional, Ardanaz, Eva, additional, Dorronsoro, Miren, additional, Key, Tim, additional, Khaw, Kay-Tee, additional, Rinaldi, Sabina, additional, Dossus, Laure, additional, Gunter, Marc, additional, Merritt, Melissa A., additional, Riboli, Elio, additional, and Kaaks, Rudolf, additional

Published
2017
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57. Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer : Results from the Finnish Maternity Cohort

Author

Fortner, Renée T, Schock, Helena, Kaaks, Rudolf, Lehtinen, Matti, Pukkala, Eero, Lakso, Hans-Åke, Tanner, Minna, Kallio, Raija, Joensuu, Heikki, Korpela, Jaana, Toriola, Adetunji T, Hallmans, Göran, Grankvist, Kjell, Zeleniuch-Jacquotte, Anne, Toniolo, Paolo, Lundin, Eva, Surcel, Heljä-Marja, Fortner, Renée T, Schock, Helena, Kaaks, Rudolf, Lehtinen, Matti, Pukkala, Eero, Lakso, Hans-Åke, Tanner, Minna, Kallio, Raija, Joensuu, Heikki, Korpela, Jaana, Toriola, Adetunji T, Hallmans, Göran, Grankvist, Kjell, Zeleniuch-Jacquotte, Anne, Toniolo, Paolo, Lundin, Eva, and Surcel, Heljä-Marja

Abstract

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk.

Published
2017
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58. Anti-Mullerian hormone and endometrial cancer : a multi-cohort study

Author

Fortner, Renée T., Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A., Brinton, Louise A., Egleston, Brian L., Falk, Roni T., Gunter, Marc J., Helzlsouer, Kathy J., Idahl, Annika, Johnson, Theron S., Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N. Charlotte, Palli, Domenico, Shu, Xiao-Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Dorgan, Joanne F., Fortner, Renée T., Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A., Brinton, Louise A., Egleston, Brian L., Falk, Roni T., Gunter, Marc J., Helzlsouer, Kathy J., Idahl, Annika, Johnson, Theron S., Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N. Charlotte, Palli, Domenico, Shu, Xiao-Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, and Dorgan, Joanne F.

Abstract

Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

Published
2017
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59. Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer : a nested case-control study in the Northern Sweden Maternity Cohort

Author

Fortner, Renee T., Tolockiene, Egle, Schock, Helena, Oda, Husam, Lakso, Hans-Åke, Hallmans, Göran, Kaaks, Rudolf, Toniolo, Paolo, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, Lundin, Eva, Fortner, Renee T., Tolockiene, Egle, Schock, Helena, Oda, Husam, Lakso, Hans-Åke, Hallmans, Göran, Kaaks, Rudolf, Toniolo, Paolo, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, and Lundin, Eva

Abstract

Background: Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones. Methods: We conducted a nested case–control study in the Northern Sweden Maternity Cohort (1975–2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection). Estrogen receptor (ER) and progesterone receptor (PR) status was available for all cases; androgen receptor (AR) data were available for 41% of cases (n = 92). Sex steroids were quantified by high-performance liquid chromatography tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression. Results: Higher concentrations of circulating progesterone in early pregnancy were inversely associated with ER+/PR+ breast cancer risk (ORlog2: 0.64 (0.41–1.00)). Higher testosterone was positively associated with ER+/PR+ disease risk (ORlog2: 1.57 (1.13–2.18)). Early pregnancy estrogens were not associated with risk, except for relatively high estradiol in the context of low progesterone (split at median, relative to low concentrations of both; OR: 1.87 (1.11–3.16)). None of the investigated hormones were associated with ER–/PR– disease, or with AR+ or AR+/ER+/PR+ disease. Conclusions: Consistent with experimental models, high progesterone in early pregnancy was associated with lower risk of ER+/PR+ breast cancer in the mother. High circulating testosterone in early pregnancy, which likely reflects nonpregnant premenopausal exposure, was associated with higher risk of ER+/PR+ disease.

Published
2017
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60. Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort

Author

Fortner, Renee T., Vitonis, Allison F., Schock, Helena, Huesing, Anika, Johnson, Theron, Fichorova, Raina N., Fashemi, Titilayo, Yamamoto, Hidemi S., Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Boutron-Ruault, Marie-Christine, Kvaskoff, Marina, Severi, Gianluca, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Matullo, Giuseppe, Mattiello, Amalia, Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Gram, Inger Torhild, Jareid, Mie, Ramon Quiros, J., Duell, Eric J., Sanchez, Maria-Jose, Dolores Chirlaque, Maria, Ardanaz, Eva, Larranaga, Nerea, Nodin, Bjorn, Brandstedt, Jenny, Idahl, Annika, Khaw, Kay-Tee, Allen, Naomi, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., Kaaks, Rudolf, Terry, Kathryn L., Fortner, Renee T., Vitonis, Allison F., Schock, Helena, Huesing, Anika, Johnson, Theron, Fichorova, Raina N., Fashemi, Titilayo, Yamamoto, Hidemi S., Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Boutron-Ruault, Marie-Christine, Kvaskoff, Marina, Severi, Gianluca, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Matullo, Giuseppe, Mattiello, Amalia, Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Gram, Inger Torhild, Jareid, Mie, Ramon Quiros, J., Duell, Eric J., Sanchez, Maria-Jose, Dolores Chirlaque, Maria, Ardanaz, Eva, Larranaga, Nerea, Nodin, Bjorn, Brandstedt, Jenny, Idahl, Annika, Khaw, Kay-Tee, Allen, Naomi, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., Kaaks, Rudolf, and Terry, Kathryn L.

Abstract

Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening. Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression. Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination. Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.

Published
2017
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61. Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium

Author

Ose, Jennifer, Poole, Elizabeth M., Schock, Helena, Lehtinen, Matti, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Visvanathan, Kala, Helzlsouer, Kathy, Buring, Julie E., Lee, I-Min, Tjonneland, Anne, Dossus, Laure, Trichopoulou, Antonia, Masala, Giovanna, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Duell, Eric J., Idahl, Annika, Travis, Ruth C., Rinaldi, Sabina, Merritt, Melissa A., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., Kaaks, Rudolf, Fortner, Renee T., Ose, Jennifer, Poole, Elizabeth M., Schock, Helena, Lehtinen, Matti, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Visvanathan, Kala, Helzlsouer, Kathy, Buring, Julie E., Lee, I-Min, Tjonneland, Anne, Dossus, Laure, Trichopoulou, Antonia, Masala, Giovanna, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Duell, Eric J., Idahl, Annika, Travis, Ruth C., Rinaldi, Sabina, Merritt, Melissa A., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., Kaaks, Rudolf, and Fortner, Renee T.

Abstract

Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case–control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02–1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03–1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60–0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC.

Published
2017
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62. Anti-Mullerian hormone and endometrial cancer : a multi-cohort study

Author

Turzanski-Fortner, Renée, Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A, Brinton, Louise A, Egleston, Brian L., Falk, Roni T, Gunter, Marc J., Helzlsouer, Kathy J, Idahl, Annika, Johnson, Theron S, Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N Charlotte, Palli, Domenico, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Dorgan, Joanne F., Turzanski-Fortner, Renée, Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A, Brinton, Louise A, Egleston, Brian L., Falk, Roni T, Gunter, Marc J., Helzlsouer, Kathy J, Idahl, Annika, Johnson, Theron S, Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N Charlotte, Palli, Domenico, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, and Dorgan, Joanne F.

Published
2017

63. Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype : Results from the EPIC Cohort

Author

Sarink, Danja, Schock, Helena, Johnson, Theron, Overvad, Kim, Holm, Marianne, Tjønneland, Anne, Boutron-Ruault, Marie Christine, His, Mathilde, Kvaskoff, Marina, Boeing, Heiner, Lagiou, Pagona, Papatesta, Eleni-Maria, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, van Gils, Carla H, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Khaw, Kay Tee, Travis, Ruth C., Dossus, Laure, Gunter, Mark, Rinaldi, Sabina, Merritt, Melissa A., Riboli, Elio, Kaaks, Rudolf, Turzanski-Fortner, Renée, Sarink, Danja, Schock, Helena, Johnson, Theron, Overvad, Kim, Holm, Marianne, Tjønneland, Anne, Boutron-Ruault, Marie Christine, His, Mathilde, Kvaskoff, Marina, Boeing, Heiner, Lagiou, Pagona, Papatesta, Eleni-Maria, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, van Gils, Carla H, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Khaw, Kay Tee, Travis, Ruth C., Dossus, Laure, Gunter, Mark, Rinaldi, Sabina, Merritt, Melissa A., Riboli, Elio, Kaaks, Rudolf, and Turzanski-Fortner, Renée

Published
2017

64. Osteoprotegerin and breast cancer risk by hormone receptor subtype : a nested case-control study in the EPIC cohort

Author

Fortner, Renée T, Sarink, Danja, Schock, Helena, Johnson, Theron, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Trichopoulou, Antonia, Naska, Androniki, Orfanos, Philippos, Palli, Domenico, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Peeters, Petra H M, Van Gils, Carla H, Weiderpass, Elisabete, Lund, Eiliv, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, María-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Key, Tim, Khaw, Kay-Tee, Rinaldi, Sabina, Dossus, Laure, Gunter, Marc, Merritt, Melissa A, Riboli, Elio, Kaaks, Rudolf, Fortner, Renée T, Sarink, Danja, Schock, Helena, Johnson, Theron, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Trichopoulou, Antonia, Naska, Androniki, Orfanos, Philippos, Palli, Domenico, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Peeters, Petra H M, Van Gils, Carla H, Weiderpass, Elisabete, Lund, Eiliv, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, María-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Key, Tim, Khaw, Kay-Tee, Rinaldi, Sabina, Dossus, Laure, Gunter, Marc, Merritt, Melissa A, Riboli, Elio, and Kaaks, Rudolf

Published
2017

65. A Comparative Study on the WCRF International/University of Bristol Methodology for Systematic Reviews of Mechanisms Underpinning Exposure-Cancer Associations

Author

Ertaylan, Gokhan, Ertaylan, Gokhan, Le Cornet, Charlotte, van Roekel, Eline H., Jung, Audrey Y., Bours, Martijn J. L., Damms-Machado, Antje, van den Brandt, Piet A., Schock, Helena, de Kok, Theo M., Theys, Jan, Arts, Ilja C. W., Kaaks, Rudolf, Weijenberg, Matty P., Fortner, Renee Turzanski, Ertaylan, Gokhan, Ertaylan, Gokhan, Le Cornet, Charlotte, van Roekel, Eline H., Jung, Audrey Y., Bours, Martijn J. L., Damms-Machado, Antje, van den Brandt, Piet A., Schock, Helena, de Kok, Theo M., Theys, Jan, Arts, Ilja C. W., Kaaks, Rudolf, Weijenberg, Matty P., and Fortner, Renee Turzanski

Abstract

The World Cancer Research Fund (WCRF) International and the University of Bristol have developed a novel framework for providing an overview of mechanistic pathways and conducting a systematic literature review of the biologically plausible mechanisms underlying exposure-cancer associations. Two teams independently applied the two-stage framework on mechanisms underpinning the association between body fatness and breast cancer to test the framework feasibility and reproducibility as part of a WCRF-commissioned validation study. In stage I, a "hypothesis-free" approach was used to provide an overview of potential intermediate mechanisms between body fatness and breast cancer. Dissimilar rankings of potential mechanisms were observed between the two teams due to different applications of the framework. In stage II, a systematic review was conducted on the insulin-like growth factor 1 receptor (IGF1R) chosen as an intermediate mechanism. Although the studies included differed, both teams found inconclusive evidence for the body fatness-IGF1R association and modest evidence linking IGF1R to breast cancer, and therefore concluded that there is currently weak evidence for IGF1R as mechanism linking body fatness to breast cancer. The framework is a good starting point for conducting systematic reviews by integrating evidence from mechanistic studies on exposure-cancer associations. On the basis of our experience, we provide recommendations for future users. (C) 2017 AACR.

Published
2017

66. Anti-Mullerian hormone and endometrial cancer: a multi-cohort study

Author

Cardiovasculaire Epi Team 3, Brain, Cancer, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Turzanski-Fortner, Renée, Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A, Brinton, Louise A, Egleston, Brian L., Falk, Roni T, Gunter, Marc J., Helzlsouer, Kathy J, Idahl, Annika, Johnson, Theron S, Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N Charlotte, Palli, Domenico, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Dorgan, Joanne F., Cardiovasculaire Epi Team 3, Brain, Cancer, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Turzanski-Fortner, Renée, Schock, Helena, Jung, Seungyoun, Allen, Naomi E., Arslan, Alan A, Brinton, Louise A, Egleston, Brian L., Falk, Roni T, Gunter, Marc J., Helzlsouer, Kathy J, Idahl, Annika, Johnson, Theron S, Kaaks, Rudolf, Krogh, Vittorio, Lundin, Eva, Merritt, Melissa A., Navarro, Carmen, Onland-Moret, N Charlotte, Palli, Domenico, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Trichopoulou, Antonia, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, and Dorgan, Joanne F.

Published
2017

67. Androgens are differentially associated with ovarian cancer subtypes in the Ovarian Cancer Cohort Consortium

Author

Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Kanker, Ose, Jennifer, Poole, Elizabeth M, Schock, Helena, Lehtinen, Matti, Arslan, Alan A, Zeleniuch-Jacquotte, Anne, Visvanathan, Kala, Helzlsouer, Kathy J, Buring, Julie E, Lee, I-Min, Tjønneland, Anne, Dossus, Laure, Trichopoulou, Antonia, Masala, Giovanna, Onland-Moret, N Charlotte, Weiderpass, Elisabete, Duell, Eric J, Idahl, Annika, Travis, Ruth C, Rinaldi, Sabina, Merritt, Melissa A, Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S, Kaaks, Rudolf, Fortner, Renée T, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Kanker, Ose, Jennifer, Poole, Elizabeth M, Schock, Helena, Lehtinen, Matti, Arslan, Alan A, Zeleniuch-Jacquotte, Anne, Visvanathan, Kala, Helzlsouer, Kathy J, Buring, Julie E, Lee, I-Min, Tjønneland, Anne, Dossus, Laure, Trichopoulou, Antonia, Masala, Giovanna, Onland-Moret, N Charlotte, Weiderpass, Elisabete, Duell, Eric J, Idahl, Annika, Travis, Ruth C, Rinaldi, Sabina, Merritt, Melissa A, Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S, Kaaks, Rudolf, and Fortner, Renée T

Published
2017

68. Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort

Author

Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Sarink, Danja, Schock, Helena, Johnson, Theron, Overvad, Kim, Holm, Marianne, Tjønneland, Anne, Boutron-Ruault, Marie Christine, His, Mathilde, Kvaskoff, Marina, Boeing, Heiner, Lagiou, Pagona, Papatesta, Eleni-Maria, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, van Gils, Carla H, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Khaw, Kay Tee, Travis, Ruth C., Dossus, Laure, Gunter, Mark, Rinaldi, Sabina, Merritt, Melissa A., Riboli, Elio, Kaaks, Rudolf, Turzanski-Fortner, Renée, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Sarink, Danja, Schock, Helena, Johnson, Theron, Overvad, Kim, Holm, Marianne, Tjønneland, Anne, Boutron-Ruault, Marie Christine, His, Mathilde, Kvaskoff, Marina, Boeing, Heiner, Lagiou, Pagona, Papatesta, Eleni-Maria, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, van Gils, Carla H, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Khaw, Kay Tee, Travis, Ruth C., Dossus, Laure, Gunter, Mark, Rinaldi, Sabina, Merritt, Melissa A., Riboli, Elio, Kaaks, Rudolf, and Turzanski-Fortner, Renée

Published
2017

69. Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium

Author

Cardiovasculaire Epi Team 3, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Ose, Jennifer, Schock, Helena, Poole, Elizabeth M, Lehtinen, Matti, Visvanathan, Kala, Helzlsouer, Kathy, Buring, Julie E, Lee, I-Min, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Trichopoulou, Antonia, Mattiello, Amalia, Onland-Moret, N Charlotte, Weiderpass, Elisabete, Sánchez, María-José, Idahl, Annika, Travis, Ruth C, Rinaldi, Sabina, Merritt, Melissa A, Wentzensen, Nicolas, Tworoger, Shelley S, Kaaks, Rudolf, Fortner, Renée T, Cardiovasculaire Epi Team 3, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Ose, Jennifer, Schock, Helena, Poole, Elizabeth M, Lehtinen, Matti, Visvanathan, Kala, Helzlsouer, Kathy, Buring, Julie E, Lee, I-Min, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Trichopoulou, Antonia, Mattiello, Amalia, Onland-Moret, N Charlotte, Weiderpass, Elisabete, Sánchez, María-José, Idahl, Annika, Travis, Ruth C, Rinaldi, Sabina, Merritt, Melissa A, Wentzensen, Nicolas, Tworoger, Shelley S, Kaaks, Rudolf, and Fortner, Renée T

Published
2017

70. Demographic, lifestyle, and other factors in relation to antimüllerian hormone levels in mostly late premenopausal women

Author

Epidemiology & Health Economics, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Jung, Seungyoun, Allen, Naomi, Arslan, Alan A., Baglietto, Laura, Brinton, Louise A., Egleston, Brian L., Falk, Roni, Fortner, Renée T., Helzlsouer, Kathy J., Idahl, Annika, Kaaks, Rudolph, Lundin, Eva, Merritt, Melissa, Onland-Moret, Charlotte, Rinaldi, Sabina, Sánchez, María José, Sieri, Sabina, Schock, Helena, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Travis, Ruth C., Tjønneland, Anne, Trichopoulou, Antonia, Tworoger, Shelley, Visvanathan, Kala, Krogh, Vittorio, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Dorgan, Joanne F., Epidemiology & Health Economics, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Jung, Seungyoun, Allen, Naomi, Arslan, Alan A., Baglietto, Laura, Brinton, Louise A., Egleston, Brian L., Falk, Roni, Fortner, Renée T., Helzlsouer, Kathy J., Idahl, Annika, Kaaks, Rudolph, Lundin, Eva, Merritt, Melissa, Onland-Moret, Charlotte, Rinaldi, Sabina, Sánchez, María José, Sieri, Sabina, Schock, Helena, Shu, Xiao Ou, Sluss, Patrick M., Staats, Paul N., Travis, Ruth C., Tjønneland, Anne, Trichopoulou, Antonia, Tworoger, Shelley, Visvanathan, Kala, Krogh, Vittorio, Weiderpass, Elisabete, Zeleniuch-Jacquotte, Anne, Zheng, Wei, and Dorgan, Joanne F.

Published
2017

71. Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort

Author

Epidemiology & Health Economics, Cardiovasculaire Epi Team 3, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Fortner, Renée T., Vitonis, Allison F., Schock, Helena, Hüsing, Anika, Johnson, Theron, Fichorova, Raina N., Fashemi, Titilayo, Yamamoto, Hidemi S., Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Boutron-Ruault, Marie Christine, Kvaskoff, Marina, Severi, Gianluca, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Matullo, Giuseppe, Mattiello, Amalia, Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Gram, Inger Torhild, Jareid, Mie, Quirós, J. Ramón, Duell, Eric J., Sánchez, Maria Jose, Chirlaque, María Dolores, Ardanaz, Eva, Larrañaga, Nerea, Nodin, Björn, Brändstedt, Jenny, Idahl, Annika, Khaw, Kay Tee, Allen, Naomi, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., Kaaks, Rudolf, Terry, Kathryn L., Epidemiology & Health Economics, Cardiovasculaire Epi Team 3, Brain, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Fortner, Renée T., Vitonis, Allison F., Schock, Helena, Hüsing, Anika, Johnson, Theron, Fichorova, Raina N., Fashemi, Titilayo, Yamamoto, Hidemi S., Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Boutron-Ruault, Marie Christine, Kvaskoff, Marina, Severi, Gianluca, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, La Vecchia, Carlo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Matullo, Giuseppe, Mattiello, Amalia, Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Gram, Inger Torhild, Jareid, Mie, Quirós, J. Ramón, Duell, Eric J., Sánchez, Maria Jose, Chirlaque, María Dolores, Ardanaz, Eva, Larrañaga, Nerea, Nodin, Björn, Brändstedt, Jenny, Idahl, Annika, Khaw, Kay Tee, Allen, Naomi, Gunter, Marc, Johansson, Mattias, Dossus, Laure, Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., Kaaks, Rudolf, and Terry, Kathryn L.

Published
2017

72. Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort

Author

MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team A, Fortner, Renée T, Sarink, Danja, Schock, Helena, Johnson, Theron, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Trichopoulou, Antonia, Naska, Androniki, Orfanos, Philippos, Palli, Domenico, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Peeters, Petra H M, Van Gils, Carla H, Weiderpass, Elisabete, Lund, Eiliv, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, María-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Key, Tim, Khaw, Kay-Tee, Rinaldi, Sabina, Dossus, Laure, Gunter, Marc, Merritt, Melissa A, Riboli, Elio, Kaaks, Rudolf, MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team A, Fortner, Renée T, Sarink, Danja, Schock, Helena, Johnson, Theron, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Trichopoulou, Antonia, Naska, Androniki, Orfanos, Philippos, Palli, Domenico, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Peeters, Petra H M, Van Gils, Carla H, Weiderpass, Elisabete, Lund, Eiliv, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, María-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Key, Tim, Khaw, Kay-Tee, Rinaldi, Sabina, Dossus, Laure, Gunter, Marc, Merritt, Melissa A, Riboli, Elio, and Kaaks, Rudolf

Published
2017

73. Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer

Author

Schock, Helena

Subjects
epithelial ovarian cancer, Medicinsk biovetenskap, Medical Bioscience, AMH, sex steroid hormones, pregnancy, placental GH, IGF-I, prospective study
Abstract

Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies. Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy. Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend

Published
2015

74. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

Author

Ose, Jennifer Fortner, Renee T. Rinaldi, Sabina Schock, Helena Overvad, Kim Tjonneland, Anne Hansen, Louise and Dossus, Laure Fournier, Agnes Baglietto, Laura Romieu, Isabelle Kuhn, Elisabetta Boeing, Heiner Trichopoulou, Antonia Lagiou, Pagona Trichopoulos, Dimitrios Palli, Domenico Masala, Giovanna Sieri, Sabina Tumino, Rosario and Sacerdote, Carlotta Mattiello, Amalia Ramon Quiros, Jose and Obon-Santacana, Mireia Larranaga, Nerea Chirlaque, Maria-Dolores and Sanchez, Maria-Jose Barricarte, Aurelio Peeters, Petra H. and Bueno-de-Mesquita, H. B(as) Onland-Moret, N. Charlotte and Braendstedt, Jenny Lundin, Eva Idahl, Annika Weiderpass, Elisabete Gram, Inger T. Lund, Eiliv Kaw, Kay-Tee and Travis, Ruth C. Merritt, Melissa A. Gunther, Marc J. Riboli, Elio Kaaks, Rudolf

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What’s new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.

Published
2015

75. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

Author

Fortner, Renee T. Ose, Jennifer Merritt, Melissa A. Schock, Helena Tjonneland, Anne Hansen, Louise Overvad, Kim and Dossus, Laure Clavel-Chapelon, Francoise Baglietto, Laura and Boeing, Heiner Trichopoulou, Antonia Benetou, Vassiliki and Lagiou, Pagona Agnoli, Claudia Mattiello, Amalia Masala, Giovanna Tumino, Rosario Sacerdote, Carlotta and Bueno-de-Mesquita, H. B(as) Onland-Moret, N. Charlotte Peeters, Petra H. Weiderpass, Elisabete Gram, Inger Torhild Duell, Eric J. Larranaga, Nerea Ardanaz, Eva Sanchez, Maria-Jose and Chirlaque, M-D Braendstedt, Jenny Idahl, Annika Lundin, Eva Khaw, Kay-Tee Wareham, Nick Travis, Ruth C. Rinaldi, Sabina Romieu, Isabelle Gunter, Marc J. Riboli, Elio and Kaaks, Rudolf

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (p(het)=0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; p(het)=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What’s new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Published
2015

76. Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort

Author

Ose, Jennifer Schock, Helena Tjonneland, Anne Hansen, Louise and Overvad, Kim Dossus, Laure Clavel-Chapelon, Francoise and Baglietto, Laura Boeing, Heiner Trichopolou, Antonia and Benetou, Vassiliki Lagiou, Pagona Masala, Giovanna and Tagliabue, Giovanna Tumino, Rosario Sacerdote, Carlotta and Mattiello, Amalia Bueno-de-Mesquita, H. B(As) Peeters, Petra H. M. Onland-Moret, N. Charlotte Weiderpass, Elisabete Gram, Inger T. Sanchez, Soledad Obon-Santacana, Mireia and Sanchez-Perez, Maria-Jose Larranaga, Nerea Huerta Castano, Jose Mara Ardanaz, Eva Brandstedt, Jenny Lundin, Eva Idahl, Annika Travis, Ruth C. Khaw, Kay-Tee Rinaldi, Sabina and Romieu, Isabelle Merritt, Melissa A. Gunter, Marc J. Riboli, Elio Kaaks, Rudolf Fortner, Renee T.

Subjects
endocrine system diseases
Abstract

Background: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP 88: ORlog2, 1.78 (1.28-2.48), P-heterogeneity

Published
2015

77. Hormone concentrations throughout uncomplicated pregnancies : a longitudinal study

Author

Schock, Helena, Zeleniuch-Jacquotte, Anne, Lundin, Eva, Grankvist, Kjell, Lakso, Hans-Åke, Idahl, Annika, Lehtinen, Matti, Surcel, Heljä-Marja, Fortner, Renee T., Schock, Helena, Zeleniuch-Jacquotte, Anne, Lundin, Eva, Grankvist, Kjell, Lakso, Hans-Åke, Idahl, Annika, Lehtinen, Matti, Surcel, Heljä-Marja, and Fortner, Renee T.

Abstract

Background: Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. Methods: We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Results: Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, r(T1 vs. T2) = 0.51 and r(T2 vs. T3) = 0.60, p < 0.01; r(T1 vs. T3) = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R-T1(2) = 16 % and R-T2(2) = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. Conclusions: One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on c

Published
2016
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78. A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort

Author

Terry, Kathryn L., Schock, Helena, Fortner, Renée T., Hüsing, Anika, Fichorova, Raina N., Yamamoto, Hidemi S., Vitonis, Allison F., Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Onland-Moret, N. Charlotte, Peeters, Petra H., Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J., Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J., Khaw, Kay-Tee, Byrne, Karl Smith, Travis, Ruth C., Gunter, Marc J., Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., Kaaks, Rudolf, Terry, Kathryn L., Schock, Helena, Fortner, Renée T., Hüsing, Anika, Fichorova, Raina N., Yamamoto, Hidemi S., Vitonis, Allison F., Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Onland-Moret, N. Charlotte, Peeters, Petra H., Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J., Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J., Khaw, Kay-Tee, Byrne, Karl Smith, Travis, Ruth C., Gunter, Marc J., Merritt, Melissa A., Riboli, Elio, Cramer, Daniel W., and Kaaks, Rudolf

Abstract

Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate earlydetection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases.

Published
2016
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79. A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Author

Terry, Kathryn L, Schock, Helena, Fortner, Renée T, Hüsing, Anika, Fichorova, Raina N, Yamamoto, Hidemi S, Vitonis, Allison F, Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H Bas, Onland-Moret, N Charlotte, Peeters, Petra H, Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J, Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J, Khaw, Kay-Tee, Smith Byrne, Karl, Travis, Ruth C, Gunter, Marc J, Merritt, Melissa A, Riboli, Elio, Cramer, Daniel, Kaaks, Rudolf, Terry, Kathryn L, Schock, Helena, Fortner, Renée T, Hüsing, Anika, Fichorova, Raina N, Yamamoto, Hidemi S, Vitonis, Allison F, Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H Bas, Onland-Moret, N Charlotte, Peeters, Petra H, Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J, Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J, Khaw, Kay-Tee, Smith Byrne, Karl, Travis, Ruth C, Gunter, Marc J, Merritt, Melissa A, Riboli, Elio, Cramer, Daniel, and Kaaks, Rudolf

Published
2016

80. A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Author

Infection & Immunity, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Epi Kanker Team 1, Terry, Kathryn L, Schock, Helena, Fortner, Renée T, Hüsing, Anika, Fichorova, Raina N, Yamamoto, Hidemi S, Vitonis, Allison F, Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H Bas, Onland-Moret, N Charlotte, Peeters, Petra H, Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J, Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J, Khaw, Kay-Tee, Smith Byrne, Karl, Travis, Ruth C, Gunter, Marc J, Merritt, Melissa A, Riboli, Elio, Cramer, Daniel, Kaaks, Rudolf, Infection & Immunity, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Epi Kanker Team 1, Terry, Kathryn L, Schock, Helena, Fortner, Renée T, Hüsing, Anika, Fichorova, Raina N, Yamamoto, Hidemi S, Vitonis, Allison F, Johnson, Theron, Overvad, Kim, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Mesrine, Sylvie, Severi, Gianluca, Dossus, Laure, Rinaldi, Sabina, Boeing, Heiner, Benetou, Vassiliki, Lagiou, Pagona, Trichopoulou, Antonia, Krogh, Vittorio, Kuhn, Elisabetta, Panico, Salvatore, Bueno-de-Mesquita, H Bas, Onland-Moret, N Charlotte, Peeters, Petra H, Gram, Inger Torhild, Weiderpass, Elisabete, Duell, Eric J, Sanchez, Maria-Jose, Ardanaz, Eva, Etxezarreta, Nerea, Navarro, Carmen, Idahl, Annika, Lundin, Eva, Jirström, Karin, Manjer, Jonas, Wareham, Nicholas J, Khaw, Kay-Tee, Smith Byrne, Karl, Travis, Ruth C, Gunter, Marc J, Merritt, Melissa A, Riboli, Elio, Cramer, Daniel, and Kaaks, Rudolf

Published
2016

81. An epidemiological model for prediction of endometrial cancer risk in Europe

Author

Cardiovasculaire Epi Team 3, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, MS MDL 1, Infection & Immunity, Hüsing, Anika, Dossus, Laure, Ferrari, Pietro, Tjønneland, Anne, Hansen, Louise, Fagherazzi, Guy, Baglietto, Laura, Schock, Helena, Chang-Claude, Jenny, Boeing, Heiner, Steffen, Annika, Trichopoulou, Antonia, Bamia, Christina, Katsoulis, Michalis, Krogh, Vittorio, Palli, Domenico, Panico, Salvatore, Onland-Moret, N. Charlotte, Peeters, Petra H., Bueno-de-Mesquita, H. Bas, Weiderpass, Elisabete, Gram, Inger T., Ardanaz, Eva, Obón-Santacana, Mireia, Navarro, Carmen, Sánchez-Cantalejo, Emilio, Etxezarreta, Nerea, Allen, Naomi E., Khaw, Kay Tee, Wareham, Nick, Rinaldi, Sabina, Romieu, Isabelle, Merritt, Melissa A., Gunter, Marc, Riboli, Elio, Kaaks, Rudolf, Cardiovasculaire Epi Team 3, Circulatory Health, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, MS MDL 1, Infection & Immunity, Hüsing, Anika, Dossus, Laure, Ferrari, Pietro, Tjønneland, Anne, Hansen, Louise, Fagherazzi, Guy, Baglietto, Laura, Schock, Helena, Chang-Claude, Jenny, Boeing, Heiner, Steffen, Annika, Trichopoulou, Antonia, Bamia, Christina, Katsoulis, Michalis, Krogh, Vittorio, Palli, Domenico, Panico, Salvatore, Onland-Moret, N. Charlotte, Peeters, Petra H., Bueno-de-Mesquita, H. Bas, Weiderpass, Elisabete, Gram, Inger T., Ardanaz, Eva, Obón-Santacana, Mireia, Navarro, Carmen, Sánchez-Cantalejo, Emilio, Etxezarreta, Nerea, Allen, Naomi E., Khaw, Kay Tee, Wareham, Nick, Rinaldi, Sabina, Romieu, Isabelle, Merritt, Melissa A., Gunter, Marc, Riboli, Elio, and Kaaks, Rudolf

Published
2016

82. Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort

Author

Fortner, Renée T., primary, Schock, Helena, additional, Kaaks, Rudolf, additional, Lehtinen, Matti, additional, Pukkala, Eero, additional, Lakso, Hans-Åke, additional, Tanner, Minna, additional, Kallio, Raija, additional, Joensuu, Heikki, additional, Korpela, Jaana, additional, Toriola, Adetunji T., additional, Hallmans, Göran, additional, Grankvist, Kjell, additional, Zeleniuch-Jacquotte, Anne, additional, Toniolo, Paolo, additional, Lundin, Eva, additional, and Surcel, Heljä-Marja, additional

Published
2016
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83. A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort

Author

Terry, Kathryn L., primary, Schock, Helena, additional, Fortner, Renée T., additional, Hüsing, Anika, additional, Fichorova, Raina N., additional, Yamamoto, Hidemi S., additional, Vitonis, Allison F., additional, Johnson, Theron, additional, Overvad, Kim, additional, Tjønneland, Anne, additional, Boutron-Ruault, Marie-Christine, additional, Mesrine, Sylvie, additional, Severi, Gianluca, additional, Dossus, Laure, additional, Rinaldi, Sabina, additional, Boeing, Heiner, additional, Benetou, Vassiliki, additional, Lagiou, Pagona, additional, Trichopoulou, Antonia, additional, Krogh, Vittorio, additional, Kuhn, Elisabetta, additional, Panico, Salvatore, additional, Bueno-de-Mesquita, H. Bas, additional, Onland-Moret, N. Charlotte, additional, Peeters, Petra H., additional, Gram, Inger Torhild, additional, Weiderpass, Elisabete, additional, Duell, Eric J., additional, Sanchez, Maria-Jose, additional, Ardanaz, Eva, additional, Etxezarreta, Nerea, additional, Navarro, Carmen, additional, Idahl, Annika, additional, Lundin, Eva, additional, Jirström, Karin, additional, Manjer, Jonas, additional, Wareham, Nicholas J., additional, Khaw, Kay-Tee, additional, Byrne, Karl Smith, additional, Travis, Ruth C., additional, Gunter, Marc J., additional, Merritt, Melissa A., additional, Riboli, Elio, additional, Cramer, Daniel W., additional, and Kaaks, Rudolf, additional

Published
2016
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85. Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort

Author

Kaaks, Rudolf Tikk, Kaja Sookthai, Disorn Schock, Helena and Johnson, Theron Tjonneland, Anne Olsen, Anja Overvad, Kim and Clavel-Chapelon, Francoise Dossus, Laure Baglietto, Laura and Rinaldi, Sabina Chajes, Veronique Romieu, Isabelle and Boeing, Heiner Schuetze, Madlen Trichopoulou, Antonia and Lagiou, Pagona Trichopoulos, Dimitrios Palli, Domenico and Sieri, Sabina Tumino, Rosario Ricceri, Fulvio Mattiello, Amalia Buckland, Genevieve Ramon Quiros, Jose Sanchez, Maria-Jose Amiano, Pilar Chirlaque, Maria-Dolores and Barricarte, Aurelio Bas Bueno-de-Mesquita, H. van Gils, Carla H. and Peeters, Petra H. Andersson, Anne Sund, Malin and Weiderpass, Elisabete Khaw, Kay-Tee Wareham, Nick Key, Timothy J. Travis, Ruth C. Merritt, Melissa A. Gunter, Marc J. Riboli, Elio Lukanova, Annekatrin

Abstract

Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1=1.56 (95% CI 1.15-2.13), p(trend)=0.02 for testosterone and ORQ4-Q1=1.33 (95% CI 0.99-1.79), p(trend)=0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1=1.32 (95% CI 0.87-2.01), p(trend)=0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1=0.94 (95% CI 0.60-1.47), p(trend)=0.34, p(het)=0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.

Published
2014

86. Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: Etiological factors or risk markers?

Author

Lukanova, Annekatrin Becker, Susen Huesing, Anika Schock, Helena Fedirko, Veronika Trepo, Elisabeth Trichopoulou, Antonia Bamia, Christina Lagiou, Pagona Benetou, Vassiliki and Trichopoulos, Dimitrios Noethlings, Ute Tjonneland, Anne and Overvad, Kim Dossus, Laure Teucher, Birgit Boeing, Heiner and Aleksandrova, Krasimira Palli, Domenico Pala, Valeria and Panico, Salvatore Tumino, Rosario Ricceri, Fulvio and Bueno-De-Mesquita, H. Bas Siersema, Peter D. Peeters, Petra H. M. Quiros, Jose Ramon Duell, Eric J. Molina-Montes, Esther and Chirlaque, Maria-Dolores Gurrea, Aurelio Barricarte and Dorronsoro, Miren Lindkvist, Bjoern Johansen, Dorthe Werner, Marten Sund, Malin Khaw, Kay-Tee Wareham, Nick Key, Timothy J. Travis, Ruth C. Rinaldi, Sabina Romieu, Isabelle and Gunter, Marc J. Riboli, Elio Jenab, Mazda Kaaks, Rudolf

Abstract

Elevated prediagnostic testosterone and insulin-like growth factor I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone-binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk [OR for top versus bottom tertile of 3.86 (1.32-11.3), p(trend) = 0.009]. As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p = 0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with prediagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as prediagnostic risk marker for HCC. (c) 2013 UICC What’s new? Testosterone and insulin-like growth factor-1 (IGF-1) are implicated in the development of hepatocellular carcinoma (HCC), though their involvement may be more complex than previously thought. Here, in a unique study population with low prevalence of hepatitis infections, an association was detected between HCC risk and increased levels of sex hormone binding globulin (SHBG) and IGF-1 prior to diagnosis. Neither testosterone nor IGF-1, however, was found to have an etiological influence in the decade before diagnosis. The results suggest that SHBG and IGF-I should be considered in the clinical evaluation of patients at increased risk of HCC.

Published
2014

87. Circulating insulin-like growth factor-1 in pregnancy and maternal risk of breast cancer

Author

Toriola, Adetunji T, Lundin, Eva, Schock, Helena, Grankvist, Kjell, Pukkala, Eero, Chen, Tianhui, Zeleniuch-Jacquotte, Anne, Toniolo, Paolo, Lehtinen, Matti, Surcel, Helja-Marja, and Lukanova, Annekatrin

Subjects
Adult, Premenopause, Pregnancy, Risk Factors, Case-Control Studies, Humans, Breast Neoplasms, Female, Insulin-Like Growth Factor I, Article
Abstract

Elevated serum concentrations of insulin-like growth factor (IGF)-I have been associated with increased risk of developing breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. This study was conducted to further characterize the association of IGF-I during pregnancy with maternal breast cancer risk.A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women younger than 40 years, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched with each case on age and date at blood donation. Serum IGF-I concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate ORs and 95% CIs.No significant associations were observed between serum IGF-I concentrations and breast cancer risk in both the overall analysis (OR, 1.08; 95% CI, 0.80-1.47) and in analyses stratified by histologic subtype, lag time to cancer diagnosis, age at pregnancy, or age at diagnosis.There was no association between IGF-I and maternal breast cancer risk during early pregnancy in this large nested case-control study.Serum IGF-I concentrations during early pregnancy may not be related to maternal risk of developing breast cancer.

Published
2011

88. Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Obon-Santacana, Mireia, Peeters, Petra H. M., Freisling, Heinz, Dossus, Laure, Clavel-Chapelon, Francoise, Baglietto, Laura, Schock, Helena, Fortner, Renee T., Boeing, Heiner, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Menendez, Virginia, Sanchez, Maria-Jose, Larranaga, Nerea, Huerta Castano, Jose Mara, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nick, Travis, Ruth C., Merritt, Melissa A., Trichopoulou, Antonia, Trichopoulos, Dimitrios, Orfanos, Philippos, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Mattiello, Amalia, Bueno-de-Mesquita, H. B., Onland-Moret, N. Charlotte, Wirfalt, Elisabeth, Stocks, Tanja, Idahl, Annika, Lundin, Eva, Skeie, Guri, Gram, Inger T., Weiderpass, Elisabete, Riboli, Elio, Duell, Eric J., Obon-Santacana, Mireia, Peeters, Petra H. M., Freisling, Heinz, Dossus, Laure, Clavel-Chapelon, Francoise, Baglietto, Laura, Schock, Helena, Fortner, Renee T., Boeing, Heiner, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Menendez, Virginia, Sanchez, Maria-Jose, Larranaga, Nerea, Huerta Castano, Jose Mara, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nick, Travis, Ruth C., Merritt, Melissa A., Trichopoulou, Antonia, Trichopoulos, Dimitrios, Orfanos, Philippos, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Mattiello, Amalia, Bueno-de-Mesquita, H. B., Onland-Moret, N. Charlotte, Wirfalt, Elisabeth, Stocks, Tanja, Idahl, Annika, Lundin, Eva, Skeie, Guri, Gram, Inger T., Weiderpass, Elisabete, Riboli, Elio, and Duell, Eric J.

Abstract

Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.

Published
2015
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89. Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes : The EPIC Cohort

Author

Ose, Jennifer, Schock, Helena, Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Dossus, Laure, Clavel-Chapelon, Francoise, Baglietto, Laura, Boeing, Heiner, Trichopolou, Antonia, Benetou, Vassiliki, Lagiou, Pagona, Masala, Giovanna, Tagliabue, Giovanna, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Bueno-de-Mesquita, H. B(As), Peeters, Petra H. M., Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Gram, Inger T., Sanchez, Soledad, Obon-Santacana, Mireia, Sanchez-Perez, Maria-Jose, Larranaga, Nerea, Huerta Castano, Jose Mara, Ardanaz, Eva, Brandstedt, Jenny, Lundin, Eva, Idahl, Annika, Travis, Ruth C., Khaw, Kay-Tee, Rinaldi, Sabina, Romieu, Isabelle, Merritt, Melissa A., Gunter, Marc J., Riboli, Elio, Kaaks, Rudolf, Fortner, Renee T., Ose, Jennifer, Schock, Helena, Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Dossus, Laure, Clavel-Chapelon, Francoise, Baglietto, Laura, Boeing, Heiner, Trichopolou, Antonia, Benetou, Vassiliki, Lagiou, Pagona, Masala, Giovanna, Tagliabue, Giovanna, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Bueno-de-Mesquita, H. B(As), Peeters, Petra H. M., Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Gram, Inger T., Sanchez, Soledad, Obon-Santacana, Mireia, Sanchez-Perez, Maria-Jose, Larranaga, Nerea, Huerta Castano, Jose Mara, Ardanaz, Eva, Brandstedt, Jenny, Lundin, Eva, Idahl, Annika, Travis, Ruth C., Khaw, Kay-Tee, Rinaldi, Sabina, Romieu, Isabelle, Merritt, Melissa A., Gunter, Marc J., Riboli, Elio, Kaaks, Rudolf, and Fortner, Renee T.

Abstract

Background: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP <= 1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist <= 80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), P-heterogeneity <= 0.01]. Conclusions: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity. Impact: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

Published
2015
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90. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

Author

Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, MS MDL 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Ose, Jennifer, Fortner, Renée T., Rinaldi, Sabina, Schock, Helena, Overvad, Kim, Tjonneland, Anne, Hansen, Louise, Dossus, Laure, Fournier, Agnes, Baglietto, Laura, Romieu, Isabelle, Kuhn, Elisabetta, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Ramon Quiros, Jose, Obõn-Santacana, Mireia, Larrañaga, Nerea, Chirlaque, María Dolores, Sánchez, María José, Barricarte, Aurelio, Peeters, Petra H., Bueno-De-Mesquita, H. B., Onland-Moret, N. Charlotte, Brändstedt, Jenny, Lundin, Eva, Idahl, Annika, Weiderpass, Elisabete, Gram, Inger T., Lund, Eiliv, Kaw, Kay Tee, Travis, Ruth C., Merritt, Melissa A., Gunther, Marc J., Riboli, Elio, Kaaks, Rudolf, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, MS MDL 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Ose, Jennifer, Fortner, Renée T., Rinaldi, Sabina, Schock, Helena, Overvad, Kim, Tjonneland, Anne, Hansen, Louise, Dossus, Laure, Fournier, Agnes, Baglietto, Laura, Romieu, Isabelle, Kuhn, Elisabetta, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Mattiello, Amalia, Ramon Quiros, Jose, Obõn-Santacana, Mireia, Larrañaga, Nerea, Chirlaque, María Dolores, Sánchez, María José, Barricarte, Aurelio, Peeters, Petra H., Bueno-De-Mesquita, H. B., Onland-Moret, N. Charlotte, Brändstedt, Jenny, Lundin, Eva, Idahl, Annika, Weiderpass, Elisabete, Gram, Inger T., Lund, Eiliv, Kaw, Kay Tee, Travis, Ruth C., Merritt, Melissa A., Gunther, Marc J., Riboli, Elio, and Kaaks, Rudolf

Published
2015

91. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

Author

MS MDL 1, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Fortner, Renée T., Ose, Jennifer, Merritt, Melissa A., Schock, Helena, Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Dossus, Laure, Clavel-Chapelon, Françoise, Baglietto, Laura, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, Lagiou, Pagona, Agnoli, Claudia, Mattiello, Amalia, Masala, Giovanna, Tumino, Rosario, Sacerdote, Carlotta, Bueno-De-Mesquita, H. B., Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Torhild Gram, Inger, Duell, Eric J., Larrañaga, Nerea, Ardanaz, Eva, Sánchez, María José, Chirlaque, M. D., Brändstedt, Jenny, Idahl, Annika, Lundin, Eva, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C., Rinaldi, Sabina, Romieu, Isabelle, Gunter, Marc J., Riboli, Elio, Kaaks, Rudolf, MS MDL 1, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Epi Kanker Team 1, Fortner, Renée T., Ose, Jennifer, Merritt, Melissa A., Schock, Helena, Tjønneland, Anne, Hansen, Louise, Overvad, Kim, Dossus, Laure, Clavel-Chapelon, Françoise, Baglietto, Laura, Boeing, Heiner, Trichopoulou, Antonia, Benetou, Vassiliki, Lagiou, Pagona, Agnoli, Claudia, Mattiello, Amalia, Masala, Giovanna, Tumino, Rosario, Sacerdote, Carlotta, Bueno-De-Mesquita, H. B., Onland-Moret, N. Charlotte, Peeters, Petra H., Weiderpass, Elisabete, Torhild Gram, Inger, Duell, Eric J., Larrañaga, Nerea, Ardanaz, Eva, Sánchez, María José, Chirlaque, M. D., Brändstedt, Jenny, Idahl, Annika, Lundin, Eva, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C., Rinaldi, Sabina, Romieu, Isabelle, Gunter, Marc J., Riboli, Elio, and Kaaks, Rudolf

Published
2015

92. Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort

Author

Ose, Jennifer, primary, Schock, Helena, additional, Tjønneland, Anne, additional, Hansen, Louise, additional, Overvad, Kim, additional, Dossus, Laure, additional, Clavel-Chapelon, Françoise, additional, Baglietto, Laura, additional, Boeing, Heiner, additional, Trichopolou, Antonia, additional, Benetou, Vassiliki, additional, Lagiou, Pagona, additional, Masala, Giovanna, additional, Tagliabue, Giovanna, additional, Tumino, Rosario, additional, Sacerdote, Carlotta, additional, Mattiello, Amalia, additional, Bueno-de-Mesquita, H. B(as)., additional, Peeters, Petra H. M., additional, Onland-Moret, N. Charlotte, additional, Weiderpass, Elisabete, additional, Gram, Inger T., additional, Sánchez, Soledad, additional, Obon-Santacana, Mireia, additional, Sànchez-Pérez, Maria-José, additional, Larrañaga, Nerea, additional, Castaño, José María Huerta, additional, Ardanaz, Eva, additional, Brändstedt, Jenny, additional, Lundin, Eva, additional, Idahl, Annika, additional, Travis, Ruth C., additional, Khaw, Kay-Tee, additional, Rinaldi, Sabina, additional, Romieu, Isabelle, additional, Merritt, Melissa A., additional, Gunter, Marc J., additional, Riboli, Elio, additional, Kaaks, Rudolf, additional, and Fortner, Renée T., additional

Published
2015
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93. An epidemiological model for prediction of endometrial cancer risk in Europe

Author

Hüsing, Anika, primary, Dossus, Laure, additional, Ferrari, Pietro, additional, Tjønneland, Anne, additional, Hansen, Louise, additional, Fagherazzi, Guy, additional, Baglietto, Laura, additional, Schock, Helena, additional, Chang-Claude, Jenny, additional, Boeing, Heiner, additional, Steffen, Annika, additional, Trichopoulou, Antonia, additional, Bamia, Christina, additional, Katsoulis, Michalis, additional, Krogh, Vittorio, additional, Palli, Domenico, additional, Panico, Salvatore, additional, Onland-Moret, N. Charlotte, additional, Peeters, Petra H., additional, Bueno-de-Mesquita, H. Bas, additional, Weiderpass, Elisabete, additional, Gram, Inger T., additional, Ardanaz, Eva, additional, Obón-Santacana, Mireia, additional, Navarro, Carmen, additional, Sánchez-Cantalejo, Emilio, additional, Etxezarreta, Nerea, additional, Allen, Naomi E., additional, Khaw, Kay Tee, additional, Wareham, Nick, additional, Rinaldi, Sabina, additional, Romieu, Isabelle, additional, Merritt, Melissa A., additional, Gunter, Marc, additional, Riboli, Elio, additional, and Kaaks, Rudolf, additional

Published
2015
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94. Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Obón-Santacana, Mireia, primary, Peeters, Petra H.M., additional, Freisling, Heinz, additional, Dossus, Laure, additional, Clavel-Chapelon, Françoise, additional, Baglietto, Laura, additional, Schock, Helena, additional, Fortner, Renée T., additional, Boeing, Heiner, additional, Tjønneland, Anne, additional, Olsen, Anja, additional, Overvad, Kim, additional, Menéndez, Virginia, additional, Sanchez, Maria-José, additional, Larrañaga, Nerea, additional, Huerta Castaño, José María, additional, Barricarte, Aurelio, additional, Khaw, Kay-Tee, additional, Wareham, Nick, additional, Travis, Ruth C., additional, Merritt, Melissa A., additional, Trichopoulou, Antonia, additional, Trichopoulos, Dimitrios, additional, Orfanos, Philippos, additional, Masala, Giovanna, additional, Sieri, Sabina, additional, Tumino, Rosario, additional, Vineis, Paolo, additional, Mattiello, Amalia, additional, Bueno-de-Mesquita, H.B., additional, Onland-Moret, N. Charlotte, additional, Wirfält, Elisabeth, additional, Stocks, Tanja, additional, Idahl, Annika, additional, Lundin, Eva, additional, Skeie, Guri, additional, Gram, Inger T., additional, Weiderpass, Elisabete, additional, Riboli, Elio, additional, and Duell, Eric J., additional

Published
2015
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95. Pre-diagnostic plasma testosterone, sex hormone binding globulin, IGF-I and hepatocellular carcinoma : etiological factors or risk markers?

Author

Lukanova, Annekatrin, Becker, Susen, Hüsing, Anika, Schock, Helena, Fedirko, Veronika, Trepo, Elisabeth, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Benetou, Vassiliki, Trichopoulos, Dimitrios, Nöthlings, Ute, Tjønneland, Anne, Overvad, Kim, Dossus, Laure, Teucher, Birgit, Boeing, Heiner, Aleksandrova, Krasimira, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Siersema, Peter D, Peeters, Petra M, Quiros, Jose Ramon, Duell, Eric J, Molina-Montes, Esther, Chirlaque, Maria-Dolores, Gurrea, Aurelio Barricarte, Dorronsoro, Miren, Lindkvist, Björn, Johansen, Dorthe, Werner, Mårten, Sund, Malin, Khaw, Kay-Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Rinaldi, Sabina, Romieu, Isabelle, Gunter, Marc J, Riboli, Elio, Jenab, Mazda, Kaaks, Rudolf, Lukanova, Annekatrin, Becker, Susen, Hüsing, Anika, Schock, Helena, Fedirko, Veronika, Trepo, Elisabeth, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Benetou, Vassiliki, Trichopoulos, Dimitrios, Nöthlings, Ute, Tjønneland, Anne, Overvad, Kim, Dossus, Laure, Teucher, Birgit, Boeing, Heiner, Aleksandrova, Krasimira, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H Bas, Siersema, Peter D, Peeters, Petra M, Quiros, Jose Ramon, Duell, Eric J, Molina-Montes, Esther, Chirlaque, Maria-Dolores, Gurrea, Aurelio Barricarte, Dorronsoro, Miren, Lindkvist, Björn, Johansen, Dorthe, Werner, Mårten, Sund, Malin, Khaw, Kay-Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Rinaldi, Sabina, Romieu, Isabelle, Gunter, Marc J, Riboli, Elio, Jenab, Mazda, and Kaaks, Rudolf

Abstract

Elevated pre-diagnostic testosterone and insulin-like growth factor-I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk (OR for top versus bottom tertile of 3.86 (1.32-11.3), ptrend =0.009). As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p=0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with pre-diagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as pre-diagnostic risk marker for HCC.

Published
2014
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96. Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer

Author

Toriola, Adetunji T., Tolockiene, Egle, Schock, Helena, Surcel, Helja-Marja, Zeleniuch-Jacquotte, Anne, Wadell, Göran, Toniolo, Paolo, Lundin, Eva, Grankvist, Kjell, Lukanova, Annekatrin, Toriola, Adetunji T., Tolockiene, Egle, Schock, Helena, Surcel, Helja-Marja, Zeleniuch-Jacquotte, Anne, Wadell, Göran, Toniolo, Paolo, Lundin, Eva, Grankvist, Kjell, and Lukanova, Annekatrin

Abstract

Background: We investigated whether the free -human chorionic gonadotropin (free -hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free -hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free -hCG does not appear to provide any additional information.

Published
2014
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97. Anti-Mullerian hormone and risk of invasive serous ovarian cancer

Author

Schock, Helena, Lundin, Eva, Vääräsmäki, M., Grankvist, Kjell, Fry, A., Dorgan, J. F., Pukkala, E., Lehtinen, M., Surcel, H. M., Lukanova, Annekatrin, Schock, Helena, Lundin, Eva, Vääräsmäki, M., Grankvist, Kjell, Fry, A., Dorgan, J. F., Pukkala, E., Lehtinen, M., Surcel, H. M., and Lukanova, Annekatrin

Abstract

Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P (trend) = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P (homogeneity) = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

Published
2014
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98. Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer

Author

Schock, Helena, Surcel, Helja-Marja, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, Lakso, Hans-Åke, Fortner, Renee Turzanski, Kaaks, Rudolf, Pukkala, Eero, Lehtinen, Matti, Toniolo, Paolo, Lundin, Eva, Schock, Helena, Surcel, Helja-Marja, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, Lakso, Hans-Åke, Fortner, Renee Turzanski, Kaaks, Rudolf, Pukkala, Eero, Lehtinen, Matti, Toniolo, Paolo, and Lundin, Eva

Abstract

Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E-2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E-2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

Published
2014
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99. Early pregnancy sex steroids and maternal breast cancer : a nested case-control study

Author

Fortner, Renée T, Schock, Helena, Kaaks, Rudolf, Lehtinen, Matti, Pukkala, Eero, Lakso, Hans-Åke, Tanner, Minna, Kallio, Raija, Joensuu, Heikki, Grankvist, Kjell, Zeleniuch-Jacquotte, Anne, Toniolo, Paolo, Lundin, Eva, Surcel, Helja-Marja, Fortner, Renée T, Schock, Helena, Kaaks, Rudolf, Lehtinen, Matti, Pukkala, Eero, Lakso, Hans-Åke, Tanner, Minna, Kallio, Raija, Joensuu, Heikki, Grankvist, Kjell, Zeleniuch-Jacquotte, Anne, Toniolo, Paolo, Lundin, Eva, and Surcel, Helja-Marja

Abstract

Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association.

Published
2014
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