Association between testosterone and cancers risk in women: a two-sample Mendelian randomization study

Abstract

Objective: Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females. Methods: Initially, a rigorous quality control process was used to identify suitable instrumental single nucleotide polymorphisms (SNPs) linked with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined via two-sample Mendelian randomization. A variety of analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Moreover, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized in order to further validate the robustness of the results. Results: Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1184, 95%CI: 1.0448-1.1971, P = 0.0083) and endometrial cancer (OR = 1.4995, 95%CI: 1.3179-1.7061, P = 9.94E-09). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1403, 95%CI: 1.0574-1.2298, P = 0.0043), cervical cancer (OR = 1.0017, 95%CI: 1.0006-1.0028, P =0.0122), and endometrial cancer (OR = 1.5046, 95%CI: 1.3103-1.7277, P = 9.06E-08). However, no causal relationship was found with BT and TT on other types of cancer (corrected P> 0.05). Conclusions: This study elucidates the role of testosterone in the development of breast cancer, endometrial cancer, and cervical cancer, while also indicating a potential tenuous link between testosterone and bladder cancer as well as skin cancer. Nonetheless, no statistically meaningful relationship between testosterone and various other types of cancer in females was observed.