The causal relationships between early sexual behaviors and cancer risks in individuals of European ancestry: a two-step Mendelian randomization study

Abstract

Abstract Background Sexual behaviors have been found to be linked to a variety of cancer risks. While The association between early sexual behaviors and cancer risk, as well as its underlying mechanism, remains unclear. Methods Two-sample Mendelian randomization (TSMR) was conducted to evaluate the association between sexual behaviors and cancer risks. We define sexual behaviors as the external manifestation represented by age at first sexual intercourse (AFS) and age at first birth (AFB). The large-scale genome-wide association studies (GWASs) of ten types of cancer were used as outcomes. Moreover, two-step Mendelian randomization was conducted to investigate the role of mediation. Causal steps approach and product of coefficients approach was performed in two-step MR study. Results Our results indicate that increased AFS was associated with the following cancers: cervical cancer [odds ratio, 0.996 95% CI = 0.994–0.998], endometrial cancer [odds ratio, 0.815 95% CI = 0.676–0.984], liver cell carcinoma [odds ratio, 0.999 95%CI = 0.999–0.999], lung cancer [odds ratio, 0.626 95% CI 0.501 to 0.783], oropharyngeal cancer [odds ratio, 0.343 95%CI = 0.173–0.681] and prostate cancer [odds ratio, 1.143 95%CI = 1.019–1.281], as well as increased AFB result in a reduced risk of certain cancers, including cervical cancer [odds ratio, 0.999 95%CI = 0.998–0.999], lung cancer [odds ratio, 0.862 95%CI = 0.791–0.940]. In two-step MR study, fasting insulin, BMI and daily cigarettes previously smoked were mediators for the relationship between sexual behaviors and the risk of certain types of cancer. Conclusions Early sexual behaviors are associated with the increased risk of cancer. Mediators for this relationship include fasting insulin, BMI and daily cigarettes previously smoked.