Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women

Dong Hang,Ane Sørlie Kværner,Kana Wu,Mingyang Song,Xiaosheng He,Hongbing Shen,Shuji Ogino,Edward L Giovannucci,Zhibin Hu,Andrew T Chan

doi:10.1186/s12916-020-01895-1

Abstract

BackgroundSex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown.MethodsWe retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses’ Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant.ResultsDuring 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24–0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17–1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02–2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99–1.78, P for trend = 0.03, respectively).ConclusionsThe findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

Highlights

Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown
Higher concentrations of sex hormone-binding globulin (SHBG) were associated with lower risk of conventional adenomas (P for trend < 0.0001), with the multivariable odds ratio (OR) of 0.47
Given the established malignant potential of advanced conventional adenoma and large serrated polyp, we focused on these high-risk lesions and examined their associations with sex hormones (Table 4)

Summary

Introduction

Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. Colorectal cancer (CRC) is highly heterogeneous and can arise from distinct precursor lesions, including conventional adenomas and serrated polyps [1]. CRC incidence is lower in women than men across all ages It appears that women are more likely to develop serrated polyps than men [8, 9]. Exposure to exogenous sex hormones, including oral contraceptives [11, 12] and postmenopausal hormone therapy [13, 14], has been linked to lower risk of CRC in some but not all studies [15, 16]. A recent meta-analysis of cohort studies found that hormone replacement therapy, but not oral contraceptives, was associated with lower risk of conventional adenoma [17]. Due to first-pass metabolism by the liver, exogenous hormones may exert certain biological effects different from those of endogenous estrogens [18]

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Discussion

Conclusion