Abstract LB-152: Associations between circulating sex hormone levels and risk of colon cancer among men from six European countries
Authors: Justin Harbs, Sabina Rinaldi, Audrey Gicquiau, Xijia Liu, Marc Gunter, Bethany Van Guelpen, Neil Murphy, Sophia Harlid
Journal: Cancer Research (2020)

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide and its incidence is rising. Identifying etiologic pathways and early detection for CRC are key to prevention and reducing mortality as the prognosis for advanced CRC, despite recent improvements in therapy, remains poor. One area of potentially measurable CRC risk factors, that is still relatively unexplored, are circulating levels of endogenous sex hormones. The incidence of CRC is greater in men than in women and a proposed hypothesis for this sex disparity is that higher levels of endogenous estrogens found in women may be protective against CRC. In addition, androgens, including testosterone, have been hypothesized to confer protective effects for CRC in men. However, few studies have evaluated the association between testosterone and CRC in men, and the limited available data suggest that any observed protective association is likely confined to colon rather than rectal cancer. The aim of this study was therefore to evaluate the relation of colon cancer risk with circulating levels of sex hormones and sex hormone binding globulin (SHBG) in a male population. Preliminary analyses included data from 461 cases of incident colon cancer and 461 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Sex hormones (estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) were measured in prediagnostic plasma samples using liquid chromatography-tandem /mass spectrometry (LC/-MS/MS), and SHBG was measured using a solid phase “sandwich” immunoradiometric assay. To test potential associations between circulating levels of sex hormones and SHBG with the risk of developing colon cancer, conditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Multivariable models were adjusted for colon cancer risk factors, including anthropometric parameters, alcohol consumption, physical activity and smoking status. In addition, models including estrone, estradiol and testosterone were adjusted for SHBG and vice versa. Preliminary results indicated an inverse association for testosterone (multivariable OR per SD: 0.80 95% CI: 0.69 - 0.93) and SHBG (multivariable OR per SD: 0.84 95% CI: 0.72 - 0.99) with CRC risk. However, after additional adjustments to SHBG and sex hormone models respectively these associations were attenuated towards the null. No associations were identified for estradiol, estrone, androstenedione, dehydroepiandrosterone, and progesterone. These preliminary results do not support an association between endogenous estrogen and colon cancer in men, while a potential association between testosterone and SHBG and colon cancer will need to be further evaluated. Citation Format: Justin Harbs, Sabina Rinaldi, Audrey Gicquiau, Xijia Liu, Marc Gunter, Bethany Van Guelpen, Neil Murphy, Sophia Harlid, Epic Network. Associations between circulating sex hormone levels and risk of colon cancer among men from six European countries [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-152.