Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer

• Published in: Endocrine-Related Cancer
• Main Authors: Schock, Helena, Surcel, Heljä-Marja, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, Lakso, Hans-Åke, Fortner, Renée Turzanski, Kaaks, Rudolf, Pukkala, Eero, Lehtinen, Matti, Toniolo, Paolo, Lundin, Eva
• Format: Text
• Language: English
• Published: 2014
• Subjects: Article; Northern Sweden
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282682/; http://www.ncbi.nlm.nih.gov/pubmed/25270324; https://doi.org/10.1530/ERC-14-0282

Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited prior studies have evaluated circulating androgens and risk of EOC, and estrogens and progesterone have been investigated in only one prior study. Further, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histologic subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations with the histologic subtypes of EOC. We identified 1,052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2,694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol, and sex hormone-binding globulin were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals [CI]. Associations between hormones and EOC differed by tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors, however, doubling of testosterone and 17-OHP concentration was associated with ~40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% risk increase for mucinous tumors. Risk of endometrioid tumors increased with higher estradiol concentrations (OR: 1.89 [1.20-2.98]). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.