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1. A framework for assessing interactions for risk stratification models: the example of ovarian cancer

Author: Phung, Minh Tung, Lee, Alice W, McLean, Karen, Anton-Culver, Hoda, Bandera, Elisa V, Carney, Michael E, Chang-Claude, Jenny, Cramer, Daniel W, Doherty, Jennifer Anne, Fortner, Renee T, Goodman, Marc T, Harris, Holly R, Jensen, Allan, Modugno, Francesmary, Moysich, Kirsten B, Pharoah, Paul DP, Qin, Bo, Terry, Kathryn L, Titus, Linda J, Webb, Penelope M, Wu, Anna H, Zeinomar, Nur, Ziogas, Argyrios, Berchuck, Andrew, Cho, Kathleen R, Hanley, Gillian E, Meza, Rafael, Mukherjee, Bhramar, Pike, Malcolm C, Pearce, Celeste Leigh, and Trabert, Britton
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Women's Health, Ovarian Cancer, Cancer, Prevention, Aetiology, 2.1 Biological and endogenous factors, 2.5 Research design and methodologies (aetiology), Good Health and Well Being, Humans, Female, Ovarian Neoplasms, Risk Factors, Risk Assessment, Case-Control Studies, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.
Published: 2023

2. Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions

Author: Dareng, Eileen O., Coetzee, Simon G., Tyrer, Jonathan P., Peng, Pei-Chen, Rosenow, Will, Chen, Stephanie, Davis, Brian D., Dezem, Felipe Segato, Seo, Ji-Heui, Nameki, Robbin, Reyes, Alberto L., Aben, Katja K.H., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Bandera, Elisa V., Beane Freeman, Laura E., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bolton, Kelly L., Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Cai, Hui, Campbell, Ian, Cannioto, Rikki, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chenevix-Trench, Georgia, Chiew, Yoke-Eng, Cook, Linda S., DeFazio, Anna, Dennis, Joe, Doherty, Jennifer A., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Ene, Gabrielle, Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Fostira, Florentia, Gentry-Maharaj, Aleksandra, Giles, Graham G., Goodman, Marc T., Gronwald, Jacek, Haiman, Christopher A., Håkansson, Niclas, Heitz, Florian, Hildebrandt, Michelle A.T., Høgdall, Estrid, Høgdall, Claus K., Huang, Ruea-Yea, Jensen, Allan, Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony N., Kelemen, Linda E., Kennedy, Catherine J., Khusnutdinova, Elza K., Kiemeney, Lambertus A., Kjaer, Susanne K., Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Larson, Melissa C., Le, Nhu D., Lester, Jenny, Li, Lian, Lubiński, Jan, Lush, Michael, Marks, Jeffrey R., Matsuo, Keitaro, May, Taymaa, McLaughlin, John R., McNeish, Iain A., Menon, Usha, Missmer, Stacey, Modugno, Francesmary, Moffitt, Melissa, Monteiro, Alvaro N., Moysich, Kirsten B., Narod, Steven A., Nguyen-Dumont, Tu, Odunsi, Kunle, Olsson, Håkan, Onland-Moret, N. Charlotte, Park, Sue K., Pejovic, Tanja, Permuth, Jennifer B., Piskorz, Anna, Prokofyeva, Darya, Riggan, Marjorie J., Risch, Harvey A., Rodríguez-Antona, Cristina, Rossing, Mary Anne, Sandler, Dale P., Setiawan, V. Wendy, Shan, Kang, Song, Honglin, Southey, Melissa C., Steed, Helen, Sutphen, Rebecca, Swerdlow, Anthony J., Teo, Soo Hwang, Terry, Kathryn L., Thompson, Pamela J., Vestrheim Thomsen, Liv Cecilie, Titus, Linda, Trabert, Britton, Travis, Ruth, Tworoger, Shelley S., Valen, Ellen, Van Nieuwenhuysen, Els, Edwards, Digna Velez, Vierkant, Robert A., Webb, Penelope M., Weinberg, Clarice R., Weise, Rayna Matsuno, Wentzensen, Nicolas, White, Emily, Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zeinomar, Nur, Zheng, Wei, Ziogas, Argyrios, Berchuck, Andrew, Goode, Ellen L., Huntsman, David G., Pearce, Celeste L., Ramus, Susan J., Sellers, Thomas A., Freedman, Matthew L., Lawrenson, Kate, Schildkraut, Joellen M., Hazelett, Dennis, Plummer, Jasmine T., Kar, Siddhartha, Jones, Michelle R., Pharoah, Paul D.P., and Gayther, Simon A.
Published: 2024
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3. Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium

Author: Trabert, Britton, Poole, Elizabeth M, White, Emily, Visvanathan, Kala, Adami, Hans-Olov, Anderson, Garnet L, Brasky, Theodore M, Brinton, Louise A, Fortner, Renee T, Gaudet, Mia, Hartge, Patricia, Hoffman-Bolton, Judith, Jones, Michael, Lacey, James V, Larsson, Susanna C, Mackenzie, Gerardo G, Schouten, Leo J, Sandler, Dale P, O’Brien, Katie, Patel, Alpa V, Peters, Ulrike, Prizment, Anna, Robien, Kim, Setiawan, V Wendy, Swerdlow, Anthony, van den Brandt, Piet A, Weiderpass, Elisabete, Wilkens, Lynne R, Wolk, Alicja, Wentzensen, Nicolas, and Tworoger, Shelley S
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Research, Orphan Drug, Cancer, Prevention, Ovarian Cancer, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, Analgesics, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Europe, Female, Follow-Up Studies, Humans, Middle Aged, Ovarian Neoplasms, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, United States, Ovarian Cancer Cohort Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: BACKGROUND:Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). METHODS:The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. RESULTS:Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. CONCLUSIONS:This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.
Published: 2019

4. Analgesic Use and Ovarian Cancer Risk

Author: Trabert, Britton, Poole, Elizabeth M, White, Emily, Visvanathan, Kala, Adami, Hans-Olov, Anderson, Garnet L, Brasky, Theodore M, Brinton, Louise A, Fortner, Renee T, Gaudet, Mia, Hartge, Patricia, Hoffman-Bolton, Judith, Jones, Michael, Lacey, James V, Larsson, Susanna C, Mackenzie, Gerardo G, Schouten, Leo J, Sandler, Dale P, O'Brien, Katie, Patel, Alpa V, Peters, Ulrike, Prizment, Anna, Robien, Kim, Setiawan, Wendy V, Swerdlow, Anthony, van den Brandt, Piet A, Weiderpass, Elisabete, Wilkens, Lynne R, Wolk, Alicja, Wentzensen, Nicolas, and Tworoger, Shelley S
Subjects: Cancer, Paediatrics and Reproductive Medicine, Obstetrics & Reproductive Medicine
Published: 2018

5. Abstract B047: Development and validation of an improved risk stratification model for ovarian cancer

Author: Phung, Minh Tung, primary, Lee, Alice W., additional, McLean, Karen, additional, Khoja, Lilah, additional, Anton-Culver, Hoda, additional, Bandera, Elisa V., additional, Doherty, Jennifer Anne, additional, Fortner, Renee T., additional, Goodman, Marc T., additional, Modugno, Francesmary, additional, Pharoah, Paul D. P., additional, Terry, Kathryn L., additional, Webb, Penelope M., additional, Wu, Anna H., additional, Berchuck, Andrew, additional, Hanley, Gillian E., additional, Mukherjee, Bhramar, additional, Pike, Malcolm C., additional, Pearce, Celeste Leigh, additional, and Trabert, Britton, additional
Published: 2024
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6. Offspring sex and risk of epithelial ovarian cancer : a multinational pooled analysis of 12 case–control studies

Author: AOCS Group, Modugno, Francesmary, Fu, Zhuxuan, Jordan, Susan J., Chang-Claude, Jenny, Fortner, Renée T., Goodman, Marc T., Moysich, Kirsten B., Schildkraut, Joellen M., Berchuck, Andrew, Bandera, Elisa V., Qin, Bo, Sutphen, Rebecca, McLaughlin, John R., Menon, Usha, Ramus, Susan J., Gayther, Simon A., Gentry-Maharaj, Aleksandra, Karpinskyj, Chloe, Pearce, Celeste L., Wu, Anna H., Risch, Harvey A., and Webb, Penelope M.
Published: 2020

7. Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival

Author: Brieger, Katharine K., Peterson, Siri, Lee, Alice W., Mukherjee, Bhramar, Bakulski, Kelly M., Alimujiang, Aliya, Anton-Culver, Hoda, Anglesio, Michael S., Bandera, Elisa V., Berchuck, Andrew, Bowtell, David D.L., Chenevix-Trench, Georgia, Cho, Kathleen R., Cramer, Daniel W., DeFazio, Anna, Doherty, Jennifer A., Fortner, Renée T., Garsed, Dale W., Gayther, Simon A., Gentry-Maharaj, Aleksandra, Goode, Ellen L., Goodman, Marc T., Harris, Holly R., Høgdall, Estrid, Huntsman, David G., Shen, Hui, Jensen, Allan, Johnatty, Sharon E., Jordan, Susan J., Kjaer, Susanne K., Kupryjanczyk, Jolanta, Lambrechts, Diether, McLean, Karen, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten, Ness, Roberta, Ramus, Susan J., Richardson, Jean, Risch, Harvey, Rossing, Mary Anne, Trabert, Britton, Wentzensen, Nicolas, Ziogas, Argyrios, Terry, Kathryn L., Wu, Anna H., Hanley, Gillian E., Pharoah, Paul, Webb, Penelope M., Pike, Malcolm C., and Pearce, Celeste Leigh
Published: 2020
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8. A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Author: Papadimitriou, Nikos, Muller, David, van den Brandt, Piet A., Geybels, Milan, Patel, Chirag J., Gunter, Marc J., Lopez, David S., Key, Timothy J., Perez-Cornago, Aurora, Ferrari, Pietro, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Agudo, Antonio, Sánchez, María-José, Overvad, Kim, Kühn, Tilman, Fortner, Renee T., Palli, Domenico, Drake, Isabel, Bjartell, Anders, Santiuste, Carmen, Bueno-de-Mesquita, Bas H., Krogh, Vittorio, Tjønneland, Anne, Lauritzen, Dorthe Furstrand, Gurrea, Aurelio Barricarte, Quirós, José Ramón, Stattin, Pär, Trichopoulou, Antonia, Martimianaki, Georgia, Karakatsani, Anna, Thysell, Elin, Johansson, Ingegerd, Ricceri, Fulvio, Tumino, Rosario, Larrañaga, Nerea, Khaw, Kay Tee, Riboli, Elio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K.
Published: 2020
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9. Reproducibility of serum oxysterols and lanosterol among postmenopausal women: Results from EPIC-Heidelberg

Author: Lu, Da-Lin, Sookthai, Disorn, Le Cornet, Charlotte, Katzke, Verena A., Johnson, Theron S., Kaaks, Rudolf, and Fortner, Renée T.
Published: 2018
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10. 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: 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

11. Obesity and Breast Cancer

Author: Fortner, Renée T., Katzke, Verena, Kühn, Tilman, Kaaks, Rudolf, Schlag, Peter M., Series editor, Senn, Hans-Jörg, Series editor, Pischon, Tobias, editor, and Nimptsch, Katharina, editor
Published: 2016
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12. Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers:A retrospective nested case-control study in two prospective cohorts

Author: Wu, Wendy Yi-Ying, Haider, Zahra, Feng, Xiaoshuang, Heath, Alicia K., Tjønneland, Anne, Agudo, Antonio, Masala, Giovanna, Robbins, Hilary A., Huerta, Maria-Jose, Guevara, Marcela, Schulze, Matthias B., Rodriguez-Barranco, Miguel, Vineis, Paolo, Tumino, Rosario, Kaaks, Rudolf, Fortner, Renee T., Sieri, Sabina, Panico, Salvatore, Nost, Therese Haugdahl, Sandanger, Torkjel M., Braaten, Tonje, Johansson, Mattias, Melin, Beatrice, Johansson, Mikael, Wu, Wendy Yi-Ying, Haider, Zahra, Feng, Xiaoshuang, Heath, Alicia K., Tjønneland, Anne, Agudo, Antonio, Masala, Giovanna, Robbins, Hilary A., Huerta, Maria-Jose, Guevara, Marcela, Schulze, Matthias B., Rodriguez-Barranco, Miguel, Vineis, Paolo, Tumino, Rosario, Kaaks, Rudolf, Fortner, Renee T., Sieri, Sabina, Panico, Salvatore, Nost, Therese Haugdahl, Sandanger, Torkjel M., Braaten, Tonje, Johansson, Mattias, Melin, Beatrice, and Johansson, Mikael
Abstract: The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts, The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample
Published: 2023

13. Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Author: Merritt, Melissa A, Tzoulaki, Ioanna, van den Brandt, Piet A, Schouten, Leo J, Tsilidis, Konstantinos K, Weiderpass, Elisabete, Patel, Chirag J, Tjønneland, Anne, Hansen, Louise, Overvad, Kim, His, Mathilde, Dartois, Laureen, Boutron-Ruault, Marie-Christine, Fortner, Renée T, Kaaks, Rudolf, Aleksandrova, Krasimira, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Bamia, Christina, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Mattiello, Amalia, Bueno-de-Mesquita, H Bas, Onland-Moret, N Charlotte, Peeters, Petra H, Skeie, Guri, Jareid, Mie, Quirós, J Ramón, Obón-Santacana, Mireia, Sánchez, María-José, Chamosa, Saioa, Huerta, José M, Barricarte, Aurelio, Dias, Joana A, Sonestedt, Emily, Idahl, Annika, Lundin, Eva, Wareham, Nicholas J, Khaw, Kay-Tee, Travis, Ruth C, Ferrari, Pietro, Riboli, Elio, and Gunter, Marc J
Published: 2016
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14. Vegetable and fruit consumption and the risk of hormone receptor–defined breast cancer in the EPIC cohort

Author: Emaus, Marleen J, Peeters, Petra HM, Bakker, Marije F, Overvad, Kim, Tjønneland, Anne, Olsen, Anja, Romieu, Isabelle, Ferrari, Pietro, Dossus, Laure, Boutron-Ruault, Marie Christine, Baglietto, Laura, Fortner, Renée T, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Polidoro, Silvia, Skeie, Guri, Lund, Eiliv, Weiderpass, Elisabete, Quirós, J Ramón, Travier, Noémie, Sánchez, María-José, Chirlaque, Maria-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Winkvist, Anna, Wennberg, Maria, Bueno-de-Mesquita, H Bas, Khaw, Kay-Tee, Travis, Ruth C, Key, Timothy J, Aune, Dagfinn, Gunter, Marc, Riboli, Elio, and van Gils, Carla H
Published: 2016
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15. Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Author: Merritt, Melissa A., Riboli, Elio, Weiderpass, Elisabete, Tsilidis, Konstantinos K., Overvad, Kim, Tjønneland, Anne, Hansen, Louise, Dossus, Laure, Fagherazzi, Guy, Baglietto, Laura, Fortner, Renée T., Ose, Jennifer, Steffen, Annika, Boeing, Heiner, Trichopoulou, Antonia, Trichopoulos, Dimitrios, Lagiou, Pagona, Masala, Giovanna, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, H. B(as), Onland-Moret, N. Charlotte, Peeters, Petra H., Hjartåker, Anette, Gram, Inger Torhild, Quirós, J. Ramón, Obón-Santacana, Mireia, Molina-Montes, Esther, Huerta Castaño, José María, Ardanaz, Eva, Chamosa, Saioa, Sonestedt, Emily, Idahl, Annika, Lundin, Eva, Khaw, Kay-Tee, Wareham, Nicholas, Travis, Ruth C., Rinaldi, Sabina, Romieu, Isabelle, Chajes, Veronique, and Gunter, Marc J.
Published: 2014
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16. Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium

Author: Fortner, Renee T., Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, Gaudet, Mia M., Tjonneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Hakansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., Schouten, Leo J., Fortner, Renee T., Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, Gaudet, Mia M., Tjonneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Hakansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., and Schouten, Leo J.
Abstract: Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.
Published: 2020

17. Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women

Author: Bauer, Scott R., Fortner, Renée T., Gates, Margaret A., Eliassen, A. Heather, Hankinson, Susan E., and Tworoger, Shelley S.
Published: 2013

18. Cigarette Smoking and Endometrial Cancer Risk:Observational and Mendelian Randomization Analyses

Author: Dimou, Niki, Omiyale, Wemimo, Biessy, Carine, Viallon, Vivian, Kaaks, Rudolf, O'Mara, Tracy A., Aglago, Elom K., Ardanaz, Eva, Bergmann, Manuela M., Bondonno, Nicola P., Braaten, Tonje, Colorado-Yohar, Sandra M., Crous-Bou, Marta, Dahm, Christina C., Fortner, Renee T., Gram, Inger T., Harlid, Sophia, Heath, Alicia K., Idahl, Annika, Kvaskoff, Marina, Nost, Therese H., Overvad, Kim, Palli, Domenico, Perez-Cornago, Aurora, Sacerdote, Carlotta, Sanchez, Maria-Jose, Schulze, Matthias B., Severi, Gianluca, Simeon, Vittorio, Tagliabue, Giovanna, Tjonneland, Anne, Truong, Therese, Tumino, Rosario, Johansson, Mattias, Weiderpass, Elisabete, Murphy, Neil, Gunter, Marc J., Lacey, Ben, Allen, Naomi E., Dossus, Laure, Dimou, Niki, Omiyale, Wemimo, Biessy, Carine, Viallon, Vivian, Kaaks, Rudolf, O'Mara, Tracy A., Aglago, Elom K., Ardanaz, Eva, Bergmann, Manuela M., Bondonno, Nicola P., Braaten, Tonje, Colorado-Yohar, Sandra M., Crous-Bou, Marta, Dahm, Christina C., Fortner, Renee T., Gram, Inger T., Harlid, Sophia, Heath, Alicia K., Idahl, Annika, Kvaskoff, Marina, Nost, Therese H., Overvad, Kim, Palli, Domenico, Perez-Cornago, Aurora, Sacerdote, Carlotta, Sanchez, Maria-Jose, Schulze, Matthias B., Severi, Gianluca, Simeon, Vittorio, Tagliabue, Giovanna, Tjonneland, Anne, Truong, Therese, Tumino, Rosario, Johansson, Mattias, Weiderpass, Elisabete, Murphy, Neil, Gunter, Marc J., Lacey, Ben, Allen, Naomi E., and Dossus, Laure
Abstract: Background: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. How-ever, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses. Methods: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined. Results: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer. Conclusions: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. Impact: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
Published: 2022

19. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author: DeVries, Amber A., Dennis, Joe, Tyrer, Jonathan P., Peng, Pei-Chen, Coetzee, Simon G., Reyes, Alberto L., Plummer, Jasmine T., Davis, Brian D., Chen, Stephanie S., Dezem, Felipe Segato, Aben, Katja K. H., Anton-Culver, Hoda, Antonenkova, Natalia N., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Berchuck, Andrew, Bogdanova, Natalia, Bogdanova-Markov, Nadja, Brenton, James D., Butzow, Ralf, Campbell, Ian, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cook, Linda S., DeFazio, Anna, Doherty, Jennifer A., Dork, Thilo, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Fortner, Renee T., Giles, Graham G., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Hakansson, Niclas, Hildebrandt, Michelle A. T., Huff, Chad, Huntsman, David G., Jensen, Allan, Kar, Siddhartha, Karlan, Beth Y., Khusnutdinova, Elza K., Kiemeney, Lambertus A., Kjaer, Susanne K., Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Le, Nhu D., Lubinski, Jan, DeVries, Amber A., Dennis, Joe, Tyrer, Jonathan P., Peng, Pei-Chen, Coetzee, Simon G., Reyes, Alberto L., Plummer, Jasmine T., Davis, Brian D., Chen, Stephanie S., Dezem, Felipe Segato, Aben, Katja K. H., Anton-Culver, Hoda, Antonenkova, Natalia N., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Berchuck, Andrew, Bogdanova, Natalia, Bogdanova-Markov, Nadja, Brenton, James D., Butzow, Ralf, Campbell, Ian, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cook, Linda S., DeFazio, Anna, Doherty, Jennifer A., Dork, Thilo, Eccles, Diana M., Eliassen, A. Heather, Fasching, Peter A., Fortner, Renee T., Giles, Graham G., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Hakansson, Niclas, Hildebrandt, Michelle A. T., Huff, Chad, Huntsman, David G., Jensen, Allan, Kar, Siddhartha, Karlan, Beth Y., Khusnutdinova, Elza K., Kiemeney, Lambertus A., Kjaer, Susanne K., Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Le, Nhu D., and Lubinski, Jan
Abstract: Background Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. Results We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (P-EOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR](HGSOC) = 5.74 del), and BRCA2 (P-HGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. Conclusions CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.
Published: 2022

20. Circulating inflammatory biomarkers, adipokines and breast cancer risk-a case-control study nested within the EPIC cohort

Author: Cairat, Manon, Rinaldi, Sabina, Navionis, Anne-Sophie, Romieu, Isabelle, Biessy, Carine, Viallon, Vivian, Olsen, Anja, Tjønneland, Anne, Fournier, Agnes, Severi, Gianluca, Kvaskoff, Marina, Fortner, Renee T., Kaaks, Rudolf, Aleksandrova, Krasimira, Schulze, Matthias B., Masala, Giovanna, Tumino, Rosario, Sieri, Sabina, Grasso, Chiara, Mattiello, Amalia, Gram, Inger T., Olsen, Karina Standahl, Agudo, Antonio, Etxezarreta, Pilar Amiano, Sanchez, Maria-Jose, Santiuste, Carmen, Barricarte, Aurelio, Monninkhof, Evelyn, Hiensch, Anouk E., Muller, David, Merritt, Melissa A., Travis, Ruth C., Weiderpass, Elisabete, Gunter, Marc J., Dossus, Laure, Cairat, Manon, Rinaldi, Sabina, Navionis, Anne-Sophie, Romieu, Isabelle, Biessy, Carine, Viallon, Vivian, Olsen, Anja, Tjønneland, Anne, Fournier, Agnes, Severi, Gianluca, Kvaskoff, Marina, Fortner, Renee T., Kaaks, Rudolf, Aleksandrova, Krasimira, Schulze, Matthias B., Masala, Giovanna, Tumino, Rosario, Sieri, Sabina, Grasso, Chiara, Mattiello, Amalia, Gram, Inger T., Olsen, Karina Standahl, Agudo, Antonio, Etxezarreta, Pilar Amiano, Sanchez, Maria-Jose, Santiuste, Carmen, Barricarte, Aurelio, Monninkhof, Evelyn, Hiensch, Anouk E., Muller, David, Merritt, Melissa A., Travis, Ruth C., Weiderpass, Elisabete, Gunter, Marc J., and Dossus, Laure
Abstract: Background Inflammation has been hypothesized to play a role in the development and progression of breast cancer and might differently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-alpha, interferon-gamma and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Methods Pre-diagnostic levels of inflammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Results Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statistically significant association was observed between inflammatory markers and breast cancer risk overall. In premenopausal women, borderline significant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77-1.03), OR= 0.88 (0.76-1.01) and OR= 0.87 (0.75-1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05-1.29), OR= 1.11 (1.01-1.23), OR= 1.10 (0.99-1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68-1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66-0.97), CRP: OR = 0.85 (0.72-1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96-1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89-1.16), CRP: OR = 1.04 (0.92-1.16)]. Conclusions Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual effect of obesity by menopausal status although this deserves further investigation
Published: 2022

21. Prediagnostic circulating concentrations of plasma insulin‐like growth factor‐I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Author: PerezCornago, Aurora, Appleby, Paul N., Tipper, Sarah, Key, Timothy J., Allen, Naomi E., Nieters, Alexandra, Vermeulen, Roel, Roulland, Sandrine, Casabonne, Delphine, Kaaks, Rudolf, Fortner, Renee T., Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Klinaki, Eleni, Hansen, Louise, Tjønneland, Anne, Bonnet, Fabrice, Fagherazzi, Guy, BoutronRuault, MarieChristine, Pala, Valeria, Masala, Giovanna, Sacerdote, Carlotta, Peeters, Petra H., BuenodeMesquita, H. B(as), Weiderpass, Elisabete, Dorronsoro, Miren, Quirós, J. Ramón, Barricarte, Aurelio, Gavrila, Diana, Agudo, Antonio, Borgquist, Signe, Rosendahl, Ann H., Melin, Beatrice, Wareham, Nick, Khaw, KayTee, Gunter, Marc, Riboli, Elio, Vineis, Paolo, and Travis, Ruth C.
Published: 2017
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22. Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium

Author: Fortner, Renee T., Fortner, Renee T., Poole, Elizabeth M., Wentzensen, Nicolas A., Trabert, Britton, White, Emily, Arslan, Alan A., Patel, Alpa, Setiawan, V. Wendy, Visvanathan, Kala, Weiderpass, Elisabete, Adami, Hans-Olov, Black, Amanda, Bernstein, Leslie, Brinton, Louise A., Buring, Julie, Clendenen, Tess, Fournier, Agnes, Fraser, Gary, Gapstur, Susan M., Gaudet, Mia M., Giles, Graham G., Gram, Inger T., Hartge, Patricia, Hoffman-Bolton, Judith, Idahl, Annika, Kaaks, Rudolf, Kirsh, Victoria A., Knutsen, Synnove, Koh, Woon-Puay, Lacey, James V., Lee, I-Min, Lundin, Eva, Merritt, Melissa A., Milne, Roger L., Onland-Moret, N. Charlotte, Peters, Ulrike, Poynter, Jenny N., Rinaldi, Sabina, Robien, Kim, Rohan, Thomas, Sanchez, Maria-Jose, Schairer, Catherine, Schouten, Leo J., Tjonneland, Anne, Townsend, Mary K., Travis, Ruth C., Trichopoulou, Antonia, van den Brandt, Piet A., Vineis, Paolo, Wilkens, Lynne, Wolk, Alicja, Yang, Hannah P., Zeleniuch-Jacquotte, Anne, Tworoger, Shelley S., Fortner, Renee T., Fortner, Renee T., Poole, Elizabeth M., Wentzensen, Nicolas A., Trabert, Britton, White, Emily, Arslan, Alan A., Patel, Alpa, Setiawan, V. Wendy, Visvanathan, Kala, Weiderpass, Elisabete, Adami, Hans-Olov, Black, Amanda, Bernstein, Leslie, Brinton, Louise A., Buring, Julie, Clendenen, Tess, Fournier, Agnes, Fraser, Gary, Gapstur, Susan M., Gaudet, Mia M., Giles, Graham G., Gram, Inger T., Hartge, Patricia, Hoffman-Bolton, Judith, Idahl, Annika, Kaaks, Rudolf, Kirsh, Victoria A., Knutsen, Synnove, Koh, Woon-Puay, Lacey, James V., Lee, I-Min, Lundin, Eva, Merritt, Melissa A., Milne, Roger L., Onland-Moret, N. Charlotte, Peters, Ulrike, Poynter, Jenny N., Rinaldi, Sabina, Robien, Kim, Rohan, Thomas, Sanchez, Maria-Jose, Schairer, Catherine, Schouten, Leo J., Tjonneland, Anne, Townsend, Mary K., Travis, Ruth C., Trichopoulou, Antonia, van den Brandt, Piet A., Vineis, Paolo, Wilkens, Lynne, Wolk, Alicja, Yang, Hannah P., Zeleniuch-Jacquotte, Anne, and Tworoger, Shelley S.
Abstract: Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in = 35 vs. 20 to <25 kg/m(2), 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
Published: 2019

23. Prognostic and Immunological Significance of ARID1A Status in Endometriosis-Associated Ovarian Carcinoma

Author: Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Kraemer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun-Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans-Walter, additional, Heitze, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix K.F, additional, Heublein, Sabine, additional, Sinn, Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, deFazio, Anna, additional, Fortner, Renee T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Toloczko-Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El-Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda B, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry-Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez-Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing-Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng-Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Koebel, Martin, additional, and Anglesio, Michael S, additional
Published: 2021
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24. Causal effects of lifetime smoking on breast and colorectal cancer risk: Mendelian randomization study

Author: Dimou, Niki, Yarmolinsky, James, Bouras, Emmanouil, Tsilidis, Konstantinos K., Martin, Richard M., Lewis, Sarah J., Gram, Inger T., Bakker, Marije F., Brenner, Hermann, Figueiredo, Jane C., Fortner, Renee T., Gruber, Stephen B., van Guelpen, Bethany, Hsu, Li, Kaaks, Rudolf, Kweon, Sun-Seog, Lin, Yi, Lindor, Noralane M., Newcomb, Polly A., Sanchez, Maria-Jose, Severi, Gianluca, Tindle, Hilary A., Tumino, Rosario, Weiderpass, Elisabete, Gunter, Marc J., Murphy, Neil, Dimou, Niki, Yarmolinsky, James, Bouras, Emmanouil, Tsilidis, Konstantinos K., Martin, Richard M., Lewis, Sarah J., Gram, Inger T., Bakker, Marije F., Brenner, Hermann, Figueiredo, Jane C., Fortner, Renee T., Gruber, Stephen B., van Guelpen, Bethany, Hsu, Li, Kaaks, Rudolf, Kweon, Sun-Seog, Lin, Yi, Lindor, Noralane M., Newcomb, Polly A., Sanchez, Maria-Jose, Severi, Gianluca, Tindle, Hilary A., Tumino, Rosario, Weiderpass, Elisabete, Gunter, Marc J., and Murphy, Neil
Abstract: Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer. Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n ¼ 126 variants) and ever having smoked regularly (n ¼ 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/ 105,974 controls) and colorectal cancer (52,775 cases/45,940 controls). Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P ¼ 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P ¼ 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P ¼ 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P ¼ 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P ¼ 0.68). Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer. Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.
Published: 2021
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25. Risk prediction for renal cell Carcinoma: Results from the European Prospective Investigation into Cancer and nutrition (EPIC) prospective cohort study

Author: Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Börje, Harbs, Justin, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, Muller, David C., Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Börje, Harbs, Justin, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, and Muller, David C.
Abstract: Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679–0.721]). Our model had slightly improved discrimination (0.714 [0.694–0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
Published: 2021
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26. Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Van Puyvelde, Heleen, Papadimitriou, Nikos, Clasen, Joanna, Muller, David, Biessy, Carine, Ferrari, Pietro, Halkjær, Jytte, Overvad, Kim, Tjønneland, Anne, Fortner, Renee T., Katzke, Verena, Schulze, Matthias B., Chiodini, Paolo, Masala, Giovanna, Pala, Valeria, Sacerdote, Carlotta, Tumino, Rosario, Bakker, Marije F., Agudo, Antonio, Ardanaz, Eva, Chirlaque Lopez, Maria Dolores, Sanchez, Maria-Jose, Ericson, Ulrika, Gylling, Bjorn, Karlsson, Therese, Manjer, Jonas, Schmidt, Julie A., Nicolas, Genevieve, Casagrande, Corinne, Weiderpass, Elisabete, Heath, Alicia K., Godderis, Lode, Van Herck, Koen, De Bacquer, Dirk, Gunter, Marc J., Huybrechts, Inge, Van Puyvelde, Heleen, Papadimitriou, Nikos, Clasen, Joanna, Muller, David, Biessy, Carine, Ferrari, Pietro, Halkjær, Jytte, Overvad, Kim, Tjønneland, Anne, Fortner, Renee T., Katzke, Verena, Schulze, Matthias B., Chiodini, Paolo, Masala, Giovanna, Pala, Valeria, Sacerdote, Carlotta, Tumino, Rosario, Bakker, Marije F., Agudo, Antonio, Ardanaz, Eva, Chirlaque Lopez, Maria Dolores, Sanchez, Maria-Jose, Ericson, Ulrika, Gylling, Bjorn, Karlsson, Therese, Manjer, Jonas, Schmidt, Julie A., Nicolas, Genevieve, Casagrande, Corinne, Weiderpass, Elisabete, Heath, Alicia K., Godderis, Lode, Van Herck, Koen, De Bacquer, Dirk, Gunter, Marc J., and Huybrechts, Inge
Abstract: (1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992-2000 and December 2013-December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 mu g/day compared to a reference intake of 205 mu g/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.
Published: 2021

27. Dietary intake of trans fatty acids and breast cancer risk in 9 European countries

Author: Matta, Michele, Huybrechts, Inge, Biessy, Carine, Casagrande, Corinne, Yammine, Sahar, Fournier, Agnes, Olsen, Karina Standahl, Lukic, Marco, Gram, Inger Torhild, Ardanaz, Eva, Sanchez, Maria-Jose, Dossus, Laure, Fortner, Renee T., Srour, Bernard, Jannasch, Franziska, Schulze, Matthias B., Amiano, Pilar, Agudo, Antonio, Colorado-Yohar, Sandra, Quiros, J. Ramon, Tumino, Rosario, Panico, Salvatore, Masala, Giovanna, Pala, Valeria, Sacerdote, Carlotta, Tjonneland, Anne, Olsen, Anja, Dahm, Christina C., Rosendahl, Ann H., Borgquist, Signe, Wennberg, Maria, Heath, Alicia K., Aune, Dagfinn, Schmidt, Julie, Weiderpass, Elisabete, Chajes, Veronique, Gunter, Marc J., Murphy, Neil, Matta, Michele, Huybrechts, Inge, Biessy, Carine, Casagrande, Corinne, Yammine, Sahar, Fournier, Agnes, Olsen, Karina Standahl, Lukic, Marco, Gram, Inger Torhild, Ardanaz, Eva, Sanchez, Maria-Jose, Dossus, Laure, Fortner, Renee T., Srour, Bernard, Jannasch, Franziska, Schulze, Matthias B., Amiano, Pilar, Agudo, Antonio, Colorado-Yohar, Sandra, Quiros, J. Ramon, Tumino, Rosario, Panico, Salvatore, Masala, Giovanna, Pala, Valeria, Sacerdote, Carlotta, Tjonneland, Anne, Olsen, Anja, Dahm, Christina C., Rosendahl, Ann H., Borgquist, Signe, Wennberg, Maria, Heath, Alicia K., Aune, Dagfinn, Schmidt, Julie, Weiderpass, Elisabete, Chajes, Veronique, Gunter, Marc J., and Murphy, Neil
Abstract: Background Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions These results support the hypothesis that higher dietary intakes of ITFAs, in pa
Published: 2021

28. Risk Prediction for Renal Cell Carcinoma:Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Prospective Cohort Study

Author: Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Borje, Harbs, Justin, Olsen, Anja, Tjonneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, Muller, David C., Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Borje, Harbs, Justin, Olsen, Anja, Tjonneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, and Muller, David C.
Abstract: Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives.Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure.Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679-0.721]). Our model had slightly improved discrimination (0.714 [0.694-0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025.Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population.Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
Published: 2021

29. The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles : An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author: Trabert, Britton, Tworoger, Shelley S., O'Brien, Katie M., Townsend, Mary K., Fortner, Renee T., Iversen, Edwin S., Hartge, Patricia, White, Emily, Amiano, Pilar, Arslan, Alan A., Bernstein, Leslie, Brinton, Louise A., Buring, Julie E., Dossus, Laure, Fraser, Gary E., Gaudet, Mia M., Giles, Graham G., Gram, Inger T., Harris, Holly R., Bolton, Judith Hoffman, Idahl, Annika, Jones, Michael E., Kaaks, Rudolf, Kirsh, Victoria A., Knutsen, Synnove F., Kvaskoff, Marina, Lacey, James, V, Lee, I-Min, Milne, Roger L., Onland-Moret, N. Charlotte, Overvad, Kim, Patel, Alpa, V, Peters, Ulrike, Poynter, Jenny N., Riboli, Elio, Robien, Kim, Rohan, Thomas E., Sandler, Dale P., Schairer, Catherine, Schouten, Leo J., Setiawan, Veronica W., Swerdlow, Anthony J., Travis, Ruth C., Trichopoulou, Antonia, van den Brandt, Piet A., Visvanathan, Kala, Wilkens, Lynne R., Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Wentzensen, Nicolas, Trabert, Britton, Tworoger, Shelley S., O'Brien, Katie M., Townsend, Mary K., Fortner, Renee T., Iversen, Edwin S., Hartge, Patricia, White, Emily, Amiano, Pilar, Arslan, Alan A., Bernstein, Leslie, Brinton, Louise A., Buring, Julie E., Dossus, Laure, Fraser, Gary E., Gaudet, Mia M., Giles, Graham G., Gram, Inger T., Harris, Holly R., Bolton, Judith Hoffman, Idahl, Annika, Jones, Michael E., Kaaks, Rudolf, Kirsh, Victoria A., Knutsen, Synnove F., Kvaskoff, Marina, Lacey, James, V, Lee, I-Min, Milne, Roger L., Onland-Moret, N. Charlotte, Overvad, Kim, Patel, Alpa, V, Peters, Ulrike, Poynter, Jenny N., Riboli, Elio, Robien, Kim, Rohan, Thomas E., Sandler, Dale P., Schairer, Catherine, Schouten, Leo J., Setiawan, Veronica W., Swerdlow, Anthony J., Travis, Ruth C., Trichopoulou, Antonia, van den Brandt, Piet A., Visvanathan, Kala, Wilkens, Lynne R., Wolk, Alicja, Zeleniuch-Jacquotte, Anne, and Wentzensen, Nicolas
Abstract: Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies.
Published: 2020
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30. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk : Results from the EPIC cohort

Author: Idahl, Annika, Le Cornet, Charlotte, Gonzalez Maldonado, Sandra, Waterboer, Tim, Bender, Noemi, Tjonneland, Anne, Hansen, Louise, Boutron-Ruault, Marie-Christine, Fournier, Agnes, Kvaskoff, Marina, Boeing, Heiner, Trichopoulou, Antonia, Valanou, Elisavet, Peppa, Eleni, Palli, Domenico, Agnoli, Claudia, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Onland-Moret, N. Charlotte, Gram, Inger T., Weiderpass, Elisabete, Quiros, Jose R., Duell, Eric J., Sanchez, Maria-Jose, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Gil, Leire, Brandstedt, Jenny, Riesbeck, Kristian, Lundin, Eva, Khaw, Kay-Tee, Perez-Cornago, Aurora, Gunter, Marc J., Dossus, Laure, Kaaks, Rudolf, Fortner, Renee T., Idahl, Annika, Le Cornet, Charlotte, Gonzalez Maldonado, Sandra, Waterboer, Tim, Bender, Noemi, Tjonneland, Anne, Hansen, Louise, Boutron-Ruault, Marie-Christine, Fournier, Agnes, Kvaskoff, Marina, Boeing, Heiner, Trichopoulou, Antonia, Valanou, Elisavet, Peppa, Eleni, Palli, Domenico, Agnoli, Claudia, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Onland-Moret, N. Charlotte, Gram, Inger T., Weiderpass, Elisabete, Quiros, Jose R., Duell, Eric J., Sanchez, Maria-Jose, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Gil, Leire, Brandstedt, Jenny, Riesbeck, Kristian, Lundin, Eva, Khaw, Kay-Tee, Perez-Cornago, Aurora, Gunter, Marc J., Dossus, Laure, Kaaks, Rudolf, and Fortner, Renee T.
Abstract: A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV‐2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead‐based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22‐4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60‐1) was associated with higher risk of EOC overall (1.36 [1.13‐1.64]) and with the serous subtype (1.44 [1.12‐1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV‐2 was associated with higher risk of endometrioid EOC (2.35 [1.24‐4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV‐2 might promote the development of endometrioid disease.
Published: 2020
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31. Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition

Author: Yammine, Sahar, Huybrechts, Inge, Biessy, Carine, Dossus, Laure, Aglago, Elom K., Naudin, Sabine, Ferrari, Pietro, Weiderpass, Elisabete, Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Mancini, Francesca R., Boutron-Ruault, Marie-Christine, Kvaskoff, Marina, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Boeing, Heiner, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Benetou, Vassiliki, Masala, Giovanna, Krogh, Vittorio, Mattiello, Amalia, Macciotta, Alessandra, Gram, Inger T., Skeie, Guri, Quiros, Jose R., Agudo, Antonio, Sanchez, Maria-Jose, Chirlaque, Maria-Dolores, Ardanaz, Eva, Gil, Leire, Sartor, Hanna, Drake, Isabel, Idahl, Annika, Lundin, Eva, Aune, Dagfinn, Ward, Heather, Merritt, Melissa A., Allen, Naomi E., Gunter, Marc J., Chajes, Veronique, Yammine, Sahar, Huybrechts, Inge, Biessy, Carine, Dossus, Laure, Aglago, Elom K., Naudin, Sabine, Ferrari, Pietro, Weiderpass, Elisabete, Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Mancini, Francesca R., Boutron-Ruault, Marie-Christine, Kvaskoff, Marina, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Boeing, Heiner, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Benetou, Vassiliki, Masala, Giovanna, Krogh, Vittorio, Mattiello, Amalia, Macciotta, Alessandra, Gram, Inger T., Skeie, Guri, Quiros, Jose R., Agudo, Antonio, Sanchez, Maria-Jose, Chirlaque, Maria-Dolores, Ardanaz, Eva, Gil, Leire, Sartor, Hanna, Drake, Isabel, Idahl, Annika, Lundin, Eva, Aune, Dagfinn, Ward, Heather, Merritt, Melissa A., Allen, Naomi E., Gunter, Marc J., and Chajes, Veronique
Abstract: Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer. Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis. Results: Apositive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintile(Q5-Q1) = 1.29; 95% confidence interval (CI) = 1.03-1.62; P-trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P-trend = 0.03) and n-3 alpha-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P-trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile(T3-T1) = 1.39; 95% CI = 0.99-1.94; P-trend = 0.06) anda-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P-trend = 0.06). Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and alpha-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer. Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
Published: 2020
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32. Exogenous hormone use and cutaneous melanoma risk in women : The European Prospective Investigation into Cancer and Nutrition

Author: Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnes, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjonneland, Anne, Olsen, Anja, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sanchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay-Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, Kvaskoff, Marina, Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnes, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjonneland, Anne, Olsen, Anja, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sanchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay-Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, and Kvaskoff, Marina
Abstract: Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
Published: 2020
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33. Ovarian Cancer Risk Factor Associations by Primary Anatomic Site:The Ovarian Cancer Cohort Consortium

Author: Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, Gaudet, Mia M., Tjønneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Hakansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., Schouten, Leo J., Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, Gaudet, Mia M., Tjønneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Hakansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., and Schouten, Leo J.
Abstract: Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.
Published: 2020

34. Genital powder use and risk of uterine cancer: A pooled analysis of prospective studies

Author: O'Brien, Katie M., primary, Tworoger, Shelley S., additional, Harris, Holly R., additional, Trabert, Britton, additional, Weinberg, Clarice R., additional, Fortner, Renee T., additional, D'Aloisio, Aimee A., additional, Kaunitz, Andrew M., additional, Wentzensen, Nicolas, additional, and Sandler, Dale P., additional
Published: 2021
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35. Association between Premenopausal Circulating Sex Steroids and Breast Cancer Risk

Author: Fortner, Renee T, primary, Eliassen, A Heather, additional, and Hankinson, Susan E, additional
Published: 2011
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36. Association between Physical Activity and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women

Author: Matthews, Charles E., Fortner, Renee T., Xu, Xia, Hankinson, Susan E., Eliassen, A. Heather, and Ziegler, Regina G.
Published: 2012

37. Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium

Author: Fortner, Renee T. Poole, Elizabeth M. Wentzensen, Nicolas A. and Trabert, Britton White, Emily Arslan, Alan A. Patel, V, Alpa and Setiawan, V. Wendy Visvanathan, Kala Weiderpass, Elisabete and Adami, Hans-Olov Black, Amanda Bernstein, Leslie and Brinton, Louise A. Buring, Julie Clendenen, V, Tess and Fournier, Agnes Fraser, Gary Gapstur, Susan M. Gaudet, Mia M. Giles, Graham G. Gram, Inger T. Hartge, Patricia and Hoffman-Bolton, Judith Idahl, Annika Kaaks, Rudolf Kirsh, Victoria A. Knutsen, Synnove Koh, Woon-Puay Lacey, Jr., James V. Lee, I-Min Lundin, Eva Merritt, Melissa A. and Milne, Roger L. Onland-Moret, N. Charlotte Peters, Ulrike and Poynter, Jenny N. Rinaldi, Sabina Robien, Kim Rohan, Thomas and Sanchez, Maria-Jose Schairer, Catherine Schouten, Leo J. and Tjonneland, Anne Townsend, Mary K. Travis, Ruth C. and Trichopoulou, Antonia van den Brandt, Piet A. Vineis, Paolo and Wilkens, Lynne Wolk, Alicja Yang, Hannah P. and Zeleniuch-Jacquotte, Anne Tworoger, Shelley S.
Abstract: Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in = 35 vs. 20 to < 25 kg/m(2), 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
Published: 2019

38. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis., Correction in: NATURE COMMUNICATIONS, Volume: 10, Article Number: 4386, DOI: 10.1038/s41467-019-12095-8
Published: 2019
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39. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

Author: Yang, Yaohua, Wu, Lang, Shu, Xiang, Lu, Yingchang, Shu, Xiao-Ou, Cai, Qiuyin, Beeghly-Fadiel, Alicia, Li, Bingshan, Ye, Fei, Berchuck, Andrew, Anton-Culver, Hoda, Banerjee, Susana, Benitez, Javier, Bjorge, Line, Brenton, James D., Butzow, Ralf, Campbell, Ian G., Chang-Claude, Jenny, Chen, Kexin, Cook, Linda S., Cramer, Daniel W., defazio, Anna, Dennis, Joe, Doherty, Jennifer A., Doerk, Thilo, Eccles, Diana M., Edwards, Digna Velez, Fasching, Peter A., Fortner, Renee T., Gayther, Simon A., Giles, Graham G., Glasspool, Rosalind M., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Harris, Holly R., Heitz, Florian, Hildebrandt, Michelle A., Hogdall, Estrid, Hogdall, Claus K., Huntsman, David G., Kar, Siddhartha P., Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne K., Koushik, Anita, Lambrechts, Diether, Le, Nhu D., Levine, Douglas A., Massuger, Leon F., Matsuo, Keitaro, May, Taymaa, McNeish, Iain A., Menon, Usha, Modugno, Francesmary, Monteiro, Alvaro N., Moorman, Patricia G., Moysich, Kirsten B., Ness, Roberta B., Nevanlinna, Heli, Olsson, Hakan, Onland-Moret, N. Charlotte, Park, Sue K., Paul, James, Pearce, Celeste L., Pejovic, Tanja, Phelan, Catherine M., Pike, Malcolm C., Ramus, Susan J., Riboli, Elio, Rodriguez-Antona, Cristina, Romieu, Isabelle, Sandler, Dale P., Schildkraut, Joellen M., Setiawan, Veronica W., Shan, Kang, Siddiqui, Nadeem, Sieh, Weiva, Stampfer, Meir J., Sutphen, Rebecca, Swerdlow, Anthony J., Szafron, Lukasz M., Teo, Soo Hwang, Tworoger, Shelley S., Tyrer, Jonathan P., Webb, Penelope M., Wentzensen, Nicolas, White, Emily, Willett, Walter C., Wolk, Alicja, Woo, Yin Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Chenevix-Trench, Georgia, Sellers, Thomas A., Pharoah, Paul D. P., Zheng, Wei, Long, Jirong, Yang, Yaohua, Wu, Lang, Shu, Xiang, Lu, Yingchang, Shu, Xiao-Ou, Cai, Qiuyin, Beeghly-Fadiel, Alicia, Li, Bingshan, Ye, Fei, Berchuck, Andrew, Anton-Culver, Hoda, Banerjee, Susana, Benitez, Javier, Bjorge, Line, Brenton, James D., Butzow, Ralf, Campbell, Ian G., Chang-Claude, Jenny, Chen, Kexin, Cook, Linda S., Cramer, Daniel W., defazio, Anna, Dennis, Joe, Doherty, Jennifer A., Doerk, Thilo, Eccles, Diana M., Edwards, Digna Velez, Fasching, Peter A., Fortner, Renee T., Gayther, Simon A., Giles, Graham G., Glasspool, Rosalind M., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Harris, Holly R., Heitz, Florian, Hildebrandt, Michelle A., Hogdall, Estrid, Hogdall, Claus K., Huntsman, David G., Kar, Siddhartha P., Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne K., Koushik, Anita, Lambrechts, Diether, Le, Nhu D., Levine, Douglas A., Massuger, Leon F., Matsuo, Keitaro, May, Taymaa, McNeish, Iain A., Menon, Usha, Modugno, Francesmary, Monteiro, Alvaro N., Moorman, Patricia G., Moysich, Kirsten B., Ness, Roberta B., Nevanlinna, Heli, Olsson, Hakan, Onland-Moret, N. Charlotte, Park, Sue K., Paul, James, Pearce, Celeste L., Pejovic, Tanja, Phelan, Catherine M., Pike, Malcolm C., Ramus, Susan J., Riboli, Elio, Rodriguez-Antona, Cristina, Romieu, Isabelle, Sandler, Dale P., Schildkraut, Joellen M., Setiawan, Veronica W., Shan, Kang, Siddiqui, Nadeem, Sieh, Weiva, Stampfer, Meir J., Sutphen, Rebecca, Swerdlow, Anthony J., Szafron, Lukasz M., Teo, Soo Hwang, Tworoger, Shelley S., Tyrer, Jonathan P., Webb, Penelope M., Wentzensen, Nicolas, White, Emily, Willett, Walter C., Wolk, Alicja, Woo, Yin Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Chenevix-Trench, Georgia, Sellers, Thomas A., Pharoah, Paul D. P., Zheng, Wei, and Long, Jirong
Abstract: DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
Published: 2019
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40. Development and validation of circulating CA125 prediction models in postmenopausal women

Author: Sasamoto, Naoko, Babic, Ana, Rosner, Bernard A., Fortner, Renee T., Vitonis, Allison F., Yamamoto, Hidemi, Fichorova, Raina N., Titus, Linda J., Tjonneland, Anne, Hansen, Louise, Kvaskoff, Marina, Fournier, Agnes, Mancini, Francesca Romana, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Karakatsani, Anna, Palli, Domenico, Grioni, Sara, Mattiello, Amalia, Tumino, Rosario, Fiano, Valentina, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Gram, Inger T., Quiros, J. Ramon, Lujan-Barroso, Leila, Sanchez, Maria-Jose, Colorado-Yohar, Sandra, Barricarte, Aurelio, Amiano, Pilar, Idahl, Annika, Lundin, Eva, Sartor, Hanna, Khaw, Kay-Tee, Key, Timothy J., Muller, David, Riboli, Elio, Gunter, Marc, Dossus, Laure, Trabert, Britton, Wentzensen, Nicolas, Kaaks, Rudolf, Cramer, Daniel W., Tworoger, Shelley S., Terry, Kathryn L., Sasamoto, Naoko, Babic, Ana, Rosner, Bernard A., Fortner, Renee T., Vitonis, Allison F., Yamamoto, Hidemi, Fichorova, Raina N., Titus, Linda J., Tjonneland, Anne, Hansen, Louise, Kvaskoff, Marina, Fournier, Agnes, Mancini, Francesca Romana, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Karakatsani, Anna, Palli, Domenico, Grioni, Sara, Mattiello, Amalia, Tumino, Rosario, Fiano, Valentina, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Gram, Inger T., Quiros, J. Ramon, Lujan-Barroso, Leila, Sanchez, Maria-Jose, Colorado-Yohar, Sandra, Barricarte, Aurelio, Amiano, Pilar, Idahl, Annika, Lundin, Eva, Sartor, Hanna, Khaw, Kay-Tee, Key, Timothy J., Muller, David, Riboli, Elio, Gunter, Marc, Dossus, Laure, Trabert, Britton, Wentzensen, Nicolas, Kaaks, Rudolf, Cramer, Daniel W., Tworoger, Shelley S., and Terry, Kathryn L.
Abstract: Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods: We developed and validated linear and dichotomous (>= 35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening b
Published: 2019
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41. Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma : results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Zamora-Ros, Raul, Alghamdi, Muath A., Cayssials, Valerie, Franceschi, Silvia, Almquist, Martin, Hennings, Joakim, Sandström, Maria, Tsilidis, Konstantinos K., Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, Hammer Bech, Bodil, Overvad, Kim, Tjonneland, Anne, Petersen, Kristina E. N., Mancini, Francesca Romana, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kuehn, Tilman, Fortner, Renee T., Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Martimianaki, Georgia, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Fasanelli, Francesca, Skeie, Guri, Braaten, Tonje, Lasheras, Cristina, Salamanca-Fernandez, Elena, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Manjer, Jonas, Wallstrom, Peter, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Khaw, Kay-Thee, Wareham, Nicholas J., Schmidt, Julie A., Aune, Dagfinn, Byrnes, Graham, Scalbert, Augustin, Agudo, Antonio, Rinaldi, Sabina, Zamora-Ros, Raul, Alghamdi, Muath A., Cayssials, Valerie, Franceschi, Silvia, Almquist, Martin, Hennings, Joakim, Sandström, Maria, Tsilidis, Konstantinos K., Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, Hammer Bech, Bodil, Overvad, Kim, Tjonneland, Anne, Petersen, Kristina E. N., Mancini, Francesca Romana, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kuehn, Tilman, Fortner, Renee T., Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Martimianaki, Georgia, Masala, Giovanna, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Fasanelli, Francesca, Skeie, Guri, Braaten, Tonje, Lasheras, Cristina, Salamanca-Fernandez, Elena, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Manjer, Jonas, Wallstrom, Peter, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Khaw, Kay-Thee, Wareham, Nicholas J., Schmidt, Julie A., Aune, Dagfinn, Byrnes, Graham, Scalbert, Augustin, Agudo, Antonio, and Rinaldi, Sabina
Abstract: Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases. Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk.
Published: 2019
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42. High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer : Results from the Ovarian Cancer Cohort Consortium

Author: Peres, Lauren C., Mallen, Adrianne R., Townsend, Mary K., Poole, Elizabeth M., Trabert, Britton, Allen, Naomi E., Arslan, Alan A., Dossus, Laure, Fortner, Renee T., Gram, Inger T., Hartge, Patricia, Idahl, Annika, Kaaks, Rudolf, Kvaskoff, Marina, Magliocco, Anthony M., Merritt, Melissa A., Quiros, J. Ramon, Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, van Gils, Carla H., Visvanathan, Kala, Wentzensen, Nicolas, Zeleniuch-Jacquotte, Anne, Tworoger, Shelley S., Peres, Lauren C., Mallen, Adrianne R., Townsend, Mary K., Poole, Elizabeth M., Trabert, Britton, Allen, Naomi E., Arslan, Alan A., Dossus, Laure, Fortner, Renee T., Gram, Inger T., Hartge, Patricia, Idahl, Annika, Kaaks, Rudolf, Kvaskoff, Marina, Magliocco, Anthony M., Merritt, Melissa A., Quiros, J. Ramon, Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, van Gils, Carla H., Visvanathan, Kala, Wentzensen, Nicolas, Zeleniuch-Jacquotte, Anne, and Tworoger, Shelley S.
Abstract: Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P-heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P-interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. Significance: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endomet
Published: 2019
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43. Predicting Circulating CA125 Levels among Healthy Premenopausal Women

Author: Sasamoto, Naoko, Babic, Ana, Rosner, Bernard A., Fortner, Renee T., Vitonis, Allison F., Yamamoto, Hidemi, Fichorova, Raina N., Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Kvaskoff, Marina, Fournier, Agnes, Mancini, Francesca Romana, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Karakatsani, Anna, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Grasso, Chiara C., Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Ramon Quiros, J., Lujan-Barroso, Leila, Rodriguez-Barranco, Miguel, Colorado-Yohar, Sandra, Barricarte, Aurelio, Dorronsoro, Miren, Idahl, Annika, Lundin, Eva, Sartor, Hanna, Khaw, Kay-Tee, Key, Timothy J., Muller, David, Riboli, Elio, Gunter, Marc J., Dossus, Laure, Kaaks, Rudolf, Cramer, Daniel W., Tworoger, Shelley S., Terry, Kathryn L., Sasamoto, Naoko, Babic, Ana, Rosner, Bernard A., Fortner, Renee T., Vitonis, Allison F., Yamamoto, Hidemi, Fichorova, Raina N., Tjonneland, Anne, Hansen, Louise, Overvad, Kim, Kvaskoff, Marina, Fournier, Agnes, Mancini, Francesca Romana, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Karakatsani, Anna, Palli, Domenico, Pala, Valeria, Mattiello, Amalia, Tumino, Rosario, Grasso, Chiara C., Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Ramon Quiros, J., Lujan-Barroso, Leila, Rodriguez-Barranco, Miguel, Colorado-Yohar, Sandra, Barricarte, Aurelio, Dorronsoro, Miren, Idahl, Annika, Lundin, Eva, Sartor, Hanna, Khaw, Kay-Tee, Key, Timothy J., Muller, David, Riboli, Elio, Gunter, Marc J., Dossus, Laure, Kaaks, Rudolf, Cramer, Daniel W., Tworoger, Shelley S., and Terry, Kathryn L.
Abstract: Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
Published: 2019
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44. Reproductive Factors, Exogenous Hormone Use, and Risk of B-Cell Non-Hodgkin Lymphoma in a Cohort of Women From the European Prospective Investigation Into Cancer and Nutrition

Author: Costas, Laura, Lujan-Barroso, Leila, Benavente, Yolanda, Allen, Naomi E., Amiano, Pilar, Ardanaz, Eva, Besson, Caroline, Boeing, Heiner, Bueno-de-Mesquita, Bas, Cervenka, Iris, Fortner, Renee T., Fournier, Agnes, Gunter, Marc, Harlid, Sophia, Maria Huerta, Jose, Jerkeman, Mats, Jirstrom, Karin, Kaaks, Rudolf, Karakatsani, Anna, Khaw, Kay-Tee, Kotanidou, Anastasia, Lund, Eiliv, Masala, Giovanna, Mattiello, Amalia, Melin, Beatrice S., Menendez, Virginia, Murphy, Neil, Nieters, Alexandra, Overvad, Kim, Riboli, Elio, Sacerdote, Carlotta, Sanchez, Maria-Jose, Schmidt, Julie A., Sieri, Sabina, Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Vermeulen, Roel, Weiderpass, Elisabete, de Sanjose, Silvia, Agudo, Antonio, Casabonne, Delphine, Costas, Laura, Lujan-Barroso, Leila, Benavente, Yolanda, Allen, Naomi E., Amiano, Pilar, Ardanaz, Eva, Besson, Caroline, Boeing, Heiner, Bueno-de-Mesquita, Bas, Cervenka, Iris, Fortner, Renee T., Fournier, Agnes, Gunter, Marc, Harlid, Sophia, Maria Huerta, Jose, Jerkeman, Mats, Jirstrom, Karin, Kaaks, Rudolf, Karakatsani, Anna, Khaw, Kay-Tee, Kotanidou, Anastasia, Lund, Eiliv, Masala, Giovanna, Mattiello, Amalia, Melin, Beatrice S., Menendez, Virginia, Murphy, Neil, Nieters, Alexandra, Overvad, Kim, Riboli, Elio, Sacerdote, Carlotta, Sanchez, Maria-Jose, Schmidt, Julie A., Sieri, Sabina, Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Vermeulen, Roel, Weiderpass, Elisabete, de Sanjose, Silvia, Agudo, Antonio, and Casabonne, Delphine
Abstract: The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.
Published: 2019
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45. Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Author: Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C, Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnès, Fortner, Renee T, Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, Bas, Peeters, Petra H, Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolores, Ardanaz, Eva, Sánchez, Maria-Jose, Quirós, Jose Ramón, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A, Khaw, Kay-Tee, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, Rinaldi, Sabina, Institut National du Cancer, Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C., Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnè, Fortner, Renee T., Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, H. Ba, Peeters, Petra H., Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolore, Ardanaz, Eva, Sánchez, Maria-Jose, Ramón Quirós, Jose, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A., Khaw, Kay-Tee, Tsilidis, Konstantinos K., Aune, Dagfinn, Riboli, Elio, and Rinaldi, Sabina
Subjects: Adult, Male, Cancer Research, GENE POLYMORPHISM, BIOMARKERS, prospective cohort, Body Mass Index, POOLED ANALYSIS, Adipokines, Risk Factors, Journal Article, Biomarkers, Tumor, Càncer de tiroide, thyroid cancer, cytokine, Humans, BREAST-CANCER, Prospective Studies, Thyroid Neoplasms, Oncology & Carcinogenesis, Obesity, Aged, ENDOMETRIAL CANCER-RISK, Science & Technology, adipokine, Interleukin-6, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Incidence, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, INTERLEUKIN-10, C-REACTIVE PROTEIN, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ADIPOSE-TISSUE, Oncology, inflammation, Case-Control Studies, Thyroid gland cancer, PLASMA ADIPONECTIN CONCENTRATIONS, Obesitat, Female, CIRCULATING ADIPONECTIN, Adiponectin, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Abstract: Source at https://doi.org/10.1002/ijc.31172. Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C‐reactive protein, interleukin (IL)‐6, IL‐10 and tumor necrosis factor (TNF)‐α and the risk of TC. A case‐control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer‐free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49–0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67–2.76, Ptrend = 0.37). Increasing levels of IL‐10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13–2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80–3.98, Ptrend = 0.17). Leptin, CRP, IL‐6 and TNF‐α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL‐10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.
Published: 2017

46. A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author: Lu, Yingchang Beeghly-Fadiel, Alicia Wu, Lang Guo, Xingyi and Li, Bingshan Schildkraut, Joellen M. Im, Hae Kyung Chen, Yian A. Permuth, Jennifer B. Reid, Brett M. Teer, Jamie K. and Moysich, Kirsten B. Andrulis, Irene L. Anton-Culver, Hoda and Arun, Banu K. Bandera, Elisa V. Barkardottir, Rosa B. and Barnes, Daniel R. Benitez, Javier Bjorge, Line Brenton, James Butzow, Ralf Caldes, Trinidad Caligo, Maria A. and Campbell, Ian Chang-Claude, Jenny Claes, Kathleen B. M. and Couch, Fergus J. Cramer, DanielW. Daly, Mary B. deFazio, Anna Dennis, Joe Diez, Orland Domchek, Susan M. Doerk, Thilo Easton, Douglas F. Eccles, Diana M. Fasching, Peter A. and Fortner, Renee T. Fountzilas, George Friedman, Eitan and Ganz, Patricia A. Garber, Judy Giles, Graham G. Godwin, Andrew K. Goldgar, David E. Goodman, Marc T. Greene, Mark H. and Gronwald, Jacek Hamann, Ute Heitz, Florian Hildebrandt, Michelle A. T. Hogdall, Claus K. Hollestelle, Antoinette and Hulick, Peter J. Huntsman, David G. Imyanitov, Evgeny N. and Isaacs, Claudine Jakubowska, Anna James, Paul Karlan, Beth Y. Kelemen, Linda E. Kiemeney, Lambertus A. Kjaer, Susanne K. Kwong, Ava Le, Nhu D. Leslie, Goska Lesueur, Fabienne and Levine, Douglas A. Mattiello, Amalia May, Taymaa and McGuffog, Lesley McNeish, Iain A. Merritt, Melissa A. and Modugno, Francesmary Montagna, Marco Neuhausen, Susan L. and Nevanlinna, Heli Nielsen, Finn C. Nikitina-Zake, Liene and Nussbaum, Robert L. Offit, Kenneth Olah, Edith Olopade, Olufunmilayo I. Olson, Sara H. Olsson, Hakan Osorio, Ana and Park, Sue K. Parsons, Michael T. Peeters, Petra H. M. and Pejovic, Tanja Peterlongo, Paolo Phelan, Catherine M. and Pujana, Miquel Angel Ramus, Susan J. Rennert, Gad Risch, Harvey Rodriguez, Gustavo C. Rodriguez-Antona, Cristina and Romieu, Isabelle Rookus, Matti A. Rossing, Mary Anne and Rzepecka, Iwona K. Sandler, Dale P. Schmutzler, Rita K. and Setiawan, Veronica W. Sharma, Priyanka Sieh, Weiva Simard, Jacques Singer, Christian F. Song, Honglin Southey, Melissa C. Spurdle, Amanda B. Sutphen, Rebecca Swerdlow, Anthony J. and Teixeira, Manuel R. Teo, Soo H. Thomassen, Mads and Tischkowitz, Marc Toland, Amanda E. Trichopoulou, Antonia and Tung, Nadine Tworoger, Shelley S. van Rensburg, Elizabeth J. and Vanderstichele, Adriaan Vega, Ana Edwards, Digna Velez Webb, Penelope M. Weitzel, Jeffrey N. Wentzensen, Nicolas White, Emily Wolk, Alicja Wu, Anna H. Yannoukakos, Drakoulis and Zorn, Kristin K. Gayther, Simon A. Antoniou, Antonis C. and Berchuck, Andrew Goode, Ellen L. Chenevix-Trench, Georgia and Sellers, Thomas A. Pharoah, Paul D. P. Zheng, Wei Long, Jirong
Subjects: endocrine system diseases, female genital diseases and pregnancy complications
Abstract: Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 x 10(-6), we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 x 10(-7), the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 x 10(-3)). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. (C) 2018 AACR.
Published: 2018

47. Anti-Mullerian hormone and risk of ovarian cancer in nine cohorts

Author: Jung, Seungyoun Allen, Naomi Arslan, Alan A. Baglietto, Laura Barricarte, Aurelio Brinton, Louise A. Egleston, Brian L. Falk, Roni T. Fortner, Renee T. Helzlsouer, Kathy J. and Gao, Yutang Idahl, Annika Kaaks, Rudolph Krogh, Vittorio and Merritt, Melissa A. Lundin, Eva Onland-Moret, N. Charlotte and Rinaldi, Sabina Schock, Helena Shu, Xiao-Ou Sluss, Patrick M. Staats, Paul N. Sacerdote, Carlotta Travis, Ruth C. and Tjonneland, Anne Trichopoulou, Antonia Tworoger, Shelley S. and Visvanathan, Kala Weiderpass, Elisabete Zeleniuch-Jacquotte, Anne Dorgan, Joanne F.
Subjects: endocrine system, endocrine system diseases, female genital diseases and pregnancy complications
Abstract: Animal and experimental data suggest that anti-Mullerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (P-trend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all P-heterogeneity: >= 0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all P-heterogeneity: >= 0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
Published: 2018

48. A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Author: Papadimitriou, Nikos, primary, Muller, David, additional, van den Brandt, Piet A., additional, Geybels, Milan, additional, Patel, Chirag J., additional, Gunter, Marc J., additional, Lopez, David S., additional, Key, Timothy J., additional, Perez-Cornago, Aurora, additional, Ferrari, Pietro, additional, Vineis, Paolo, additional, Weiderpass, Elisabete, additional, Boeing, Heiner, additional, Agudo, Antonio, additional, Sánchez, María-José, additional, Overvad, Kim, additional, Kühn, Tilman, additional, Fortner, Renee T., additional, Palli, Domenico, additional, Drake, Isabel, additional, Bjartell, Anders, additional, Santiuste, Carmen, additional, Bueno-de-Mesquita, Bas H., additional, Krogh, Vittorio, additional, Tjønneland, Anne, additional, Lauritzen, Dorthe Furstrand, additional, Gurrea, Aurelio Barricarte, additional, Quirós, José Ramón, additional, Stattin, Pär, additional, Trichopoulou, Antonia, additional, Martimianaki, Georgia, additional, Karakatsani, Anna, additional, Thysell, Elin, additional, Johansson, Ingegerd, additional, Ricceri, Fulvio, additional, Tumino, Rosario, additional, Larrañaga, Nerea, additional, Khaw, Kay Tee, additional, Riboli, Elio, additional, Tzoulaki, Ioanna, additional, and Tsilidis, Konstantinos K., additional
Published: 2019
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49. Sex hormone binding globulin and risk of breast cancer: a Mendelian randomization study

Author: Dimou, Niki L, primary, Papadimitriou, Nikos, additional, Gill, Dipender, additional, Christakoudi, Sofia, additional, Murphy, Neil, additional, Gunter, Marc J, additional, Travis, Ruth C, additional, Key, Tim J, additional, Fortner, Renee T, additional, Haycock, Philip C, additional, Lewis, Sarah J, additional, Muir, Kenneth, additional, Martin, Richard M, additional, and Tsilidis, Konstantinos K, additional
Published: 2019
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50. Adipokines and inflammation markers and risk of differentiated thyroid carcinoma : The EPIC study

Author: Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C, Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnès, Fortner, Renee T, Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, H B As, Peeters, Petra H, Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolores, Ardanaz, Eva, Sánchez, Maria-Jose, Ramón Quirós, Jose, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A, Khaw, Kay-Tee, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, Rinaldi, Sabina, Dossus, Laure, Franceschi, Silvia, Biessy, Carine, Navionis, Anne-Sophie, Travis, Ruth C, Weiderpass, Elisabete, Scalbert, Augustin, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bonnet, Fabrice, Fournier, Agnès, Fortner, Renee T, Kaaks, Rudolf, Aleksandrova, Krasimira, Trichopoulou, Antonia, La Vecchia, Carlo, Peppa, Eleni, Tumino, Rosario, Panico, Salvatore, Palli, Domenico, Agnoli, Claudia, Vineis, Paolo, Bueno-de-Mesquita, H B As, Peeters, Petra H, Skeie, Guri, Zamora-Ros, Raul, Chirlaque, María-Dolores, Ardanaz, Eva, Sánchez, Maria-Jose, Ramón Quirós, Jose, Dorronsoro, Miren, Sandström, Maria, Nilsson, Lena Maria, Schmidt, Julie A, Khaw, Kay-Tee, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, and Rinaldi, Sabina
Abstract: Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.
Published: 2018
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