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

Abstract

Background Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. Methods We 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. Results During 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). Conclusions The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

Disparate age and sex distribution of sessile serrated lesions and conventional adenomas in an outpatient colonoscopy population–implications for colorectal cancer screening?

“…Whether or not sex hormones and adiposity contribute to SSL risk in young women remains unclear. Such a link between sex hormones and early colorectal carcinogenesis has been suggested in a previous study by Hang et al; however, specific associations for SSLs were not explored [36]. Although the diverticular disease was not associated with SSL detection in our study, there was an association between diverticular disease and adenomas in our univariate analysis and also in previous studies and meta-analyses [2,37,38].…”

The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics

“…One possible mechanism to explain this phenomenon was the interaction of sex hormones and their regulators in CRC. The sex hormones were suggested as contributors for gender disparity in incidence and mortality of CRC [ 54 , 55 , 56 , 57 ]. Notably, despite its ambiguous and contradictory role in CRC, testosterone was suggested to be involved in CRC development and prognosis [ 56 , 58 ], and the androgen was suggested to regulate MMPs (MMP-2) and the cellular processes of intimal hyperplasia [ 59 ].…”

Metformin and testosterone replacement therapy inversely associated with hormone‐associated cancers (prostate, colorectal and male breast cancers) among older White and Black men

“…[1][2][3] Because endogenous testosterone has been previously associated with prostate, colorectal and male breast cancer, they will be referred as hormone-associated cancers, HRCs, when they are combined. [4][5][6][7][8][9][10][11] Colorectal cancer is investigated as a hormone-associated cancer and not as a hormonedependent or hormone-caused cancer; therefore, this potential hormone-cancer relationship has potential translational applications for preventive diagnosis, risk stratification and treatment. 6,8,9,11 A retrospective cohort study that emulated an intent-to-treat analysis on 95,820 participants found a similar incidence of total cancer, prostate, colorectal and postmenopausal breast cancers among those who used metformin compared with those who used sulfonylureas.…”

“…[4][5][6][7][8][9][10][11] Colorectal cancer is investigated as a hormone-associated cancer and not as a hormonedependent or hormone-caused cancer; therefore, this potential hormone-cancer relationship has potential translational applications for preventive diagnosis, risk stratification and treatment. 6,8,9,11 A retrospective cohort study that emulated an intent-to-treat analysis on 95,820 participants found a similar incidence of total cancer, prostate, colorectal and postmenopausal breast cancers among those who used metformin compared with those who used sulfonylureas. 1 A recent meta-analysis of 18 cohort studies did not show an association between metformin and prostate cancer.…”