Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study

Abstract

Objective In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. Methods We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. Results Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09–1.26, P = 2.51E−05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48–0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36–0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001–1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. Conclusion This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study

“…Similar to the MR study of Larsson et al on the effect of estradiol on lung cancer in 198,825 women in UK Biobank (24), we did not nd evidence of a causal association. To our knowledge, the only MR study investigating the causal effect of testosterone on lung cancer was performed among men (27). In this study, Chang et al reported no causal association of bioavailable testosterone and total testosterone with lung cancer risk (27).…”

“…To our knowledge, the only MR study investigating the causal effect of testosterone on lung cancer was performed among men (27). In this study, Chang et al reported no causal association of bioavailable testosterone and total testosterone with lung cancer risk (27). Nevertheless, effects of sex hormones are heterogenous between males and females (22) and may vary among lung cancer subtypes.…”

Causal relationships between prostate cancer and six psychiatri c disorders: A two-sample Mendelian randomization study

“…The link between total testosterone and the incidence of PCa is still debatable, though. There is no compelling epidemiological evidence between testosterone and PCa [33,34] , despite the fact that testosterone has been demonstrated to cause PCa in rats [35,36] .…”

Association Between Sex Hormones Levels and Cancer Prevalence in Women, Especially Breast Cancer

“…Testosterone is another important sex hormone that plays an important role in male sexual development and maintenance of male characteristics. In addition to this, testosterone has multiple target organs of action and has a regulatory effect on the function of several systems and organs of the body [11] . Circulating testosterone is converted to two important metabolites in peripheral tissue species: dihydrotestosterone and estradiol [12] .…”

“…Circulating testosterone is converted to two important metabolites in peripheral tissue species: dihydrotestosterone and estradiol [12] . Serum testosterone levels are closely related to the occurrence, treatment, and prognosis of many cancers [11,13] . In a study on testosterone and sex hormone-binding globulin and 19 cancers, it was shown that serum testosterone levels were associated with cancer prevalence in either male or female populations [14] .…”