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Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case–control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case–control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (

Background: A subset of high grade serous carcinomas may arise from the fallopian tube, while some endometrioid and clear cell carcinomas may derive from endometrial tissue. Previous studies have suggested differences in ovarian cancer risk factors by histologic subtypes, but had limited sample sizes. In the Ovarian Cancer Cohort Consortium (OC3), we evaluated associations of reproductive, hormonal, demographic and lifestyle factors, and family history of cancer with ovarian cancer subtypes. Identification of potential differences in associations among subtypes is important for clarifying ovarian cancer etiology and for developing novel prevention and risk prediction approaches. Methods: Among over 1.2 million women from 21 cohort studies, 4,347 ovarian cancers with histology information were identified during follow-up (3223 serous, 555 endometrioid, 316 mucinous, 253 clear cell). We used competing risks Cox proportional hazards regression to compute risk factor associations by histologic subtype. Models were stratified on study and year of birth and adjusted for age, parity and oral contraceptive use; subtype heterogeneity was evaluated by a likelihood ratio test. Unsupervised hierarchical clustering was used to evaluate patterns of risk factors by histology. Results: Most risk factors showed significant heterogeneity across histologic subtypes. Higher parity was most strongly associated with lower risks of endometrioid (RR per child: 0.79; 95%CI: 0.74-0.85) and clear cell (RR: 0.69; 95%CI: 0.61-0.78) carcinomas (p-het5 years) was associated with endometrioid carcinomas (RR: 2.23; 95% CI: 1.46-3.42) and serous carcinomas (RR: 1.66; 95% CI: 1.44-1.92), and inversely associated with clear cell carcinomas (RR: 0.43; 95% CI: 0.20-0.91; p-het = 0.001). Family history of breast cancer was associated with increased risk of serous carcinomas (RR:1.13; 95% CI:1.02-1.27) and endometrioid carcinomas (RR: 1.44; 95% CI: 1.12-1.87; p-het = 0.02). Smoking (per 20 pack years) showed a positive association with mucinous carcinomas (RR: 1.38; 95% CI: 1.09-1.75) and an inverse association with clear cell carcinomas (RR:0.62; 95% CI: 0.46-0.85; p-het = 0.001). In unsupervised hierarchical clustering, serous and mucinous carcinomas clustered in one group and endometrioid and clear cell carcinomas in the other. Conclusion: Our results demonstrate heterogeneous associations of risk factors with ovarian cancer subtypes, supporting the hypothesis that the subtypes develop through different pathways. Most established risk factors were more strongly associated with non-serous carcinomas, suggesting that risk prediction may be more challenging for serous cancers, the most fatal subtype. Citation Format: Nicolas A. Wentzensen, Elizabeth Poole, Alan A. Arslan, Alpa V. Patel, V Wendy Setiawan, Kala Visvanathan, Elisabete Weiderpass, Emily White, Hans-Olov Adami, Louise A. Brinton, Leslie Bernstein, Julie Buring, Lesley M. Butler, Saioa Chamosa, Tess V. Clendenen, Laure Dossus, Renee Fortner, Susan M. Gapstur, Mia M. Gaudet, Inger Torhild Gram, Patricia Hartge, Judith Hoffman-Bolton, Annika Idahl, Michael Jones, Rudolf Kaaks, Vivki Kirsh, Woon-Puay Koh, James V. Lacey, I-Min Lee, Eva Lundin, Melissa Merritt, Ulrike Peters, Jenny Poynter, Sabina Rinaldi, Kim Robien, Thomas Rohan, Dale P. Sandler, Leo J. Schouten, Louise Sjöholm, Sabina Sieri, Anthony Swerdlow, Anne Tjønneland, Britton Trabert, Lynne Wilkens, Alicja Wolk, Hannah P. Yang, Anne Zeleniuch-Jacquotte, Shelley S. Tworoger. Ovarian cancer risk factors by histologic subtypes: evidence for etiologic heterogeneity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 854. doi:10.1158/1538-7445.AM2015-854

Objective: Studies regarding the association between smoking and risk of epithelial ovarian cancer (EOC) are few and inconsistent. The purpose of this study was to examine the association between smoking and subtypes of EOC in the EPIC cohort. Material and methods : The EPIC cohort is a large, multi-centre prospective study to investigate the relations of nutritional, lifestyle, metabolic and genetic risk factors and cancer incidence. It was initiated in 1992 in ten European countries (Sweden, Denmark, Norway, the Netherlands, United Kingdom, France, Germany, Spain, Italy and Greece). The questionnaires included data about dietary, lifestyle and health factors. Information about tobacco smoking was collected from individuals in all participating countries. Subjects were asked if they smoked cigarettes currently and whether they had smoked in the past. Information was available on current and life-time number of cigarettes per day, duration of smoking, age started smoking and age of smoking cessation (for former smokers). Incident cancer cases were identified through several methods, including record linkage with regional cancer registries, health insurance records, cancer and pathology registries and active follow-up of study subjects. We used Cox proportional hazard regression models to estimate hazard ratio (RR) of EOC with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables and stratifying by center. Results: Altogether 836 [731 (87%) invasive, 67(8%) borderline and 38(5%) unclassified] incident EOC cases were identified among the 326,788 women during an average of 6 years of follow-up. The tumours were classified as 400 serous, 83 mucinous, 80 endometroid and 35 clear cell and 238 unspecified. Altogether, 11% of the serous and 28% of the mucinous tumors was classified as borderline tumors. Twenty-three percent of the women reported to be former and 20% current smokers. The multivariate models showed that current smokers had a 10 % increased risk for EOC overall [RR=1.1(95 % CI 0.9 − 1.4)], a 70% increased risk of borderline tumors [RR=1.7(95 % CI 0.9 − 3.0) and an 80 % [RR=1.8(95 % CI 1.1 − 3.0)] increased risk of mucinous tumors. Only the latter association achieved statistical significance. A positive trend test for age started smoking ( Conclusion: Our results support the notion that smoking increases the risk of mucinous EOC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1831.