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

Area of Science:

• Endocrinology and Oncology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between testosterone and cancer.
• The causal relationship and magnitude remain unclear for various cancer types.

Purpose of the Study:

• To assess the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with the risk of 22 cancers in men using Mendelian randomization.
• To clarify the role of testosterone in the development of specific cancers.

Main Methods:

• Two-sample Mendelian randomization study utilizing publicly available GWAS summary statistics.
• Inverse variance weighted (IVW) method for causal estimates.
• Sensitivity analyses were performed to ensure the validity of causal inferences.

Main Results:

• Bioavailable testosterone (BT) showed a significant association with increased prostate cancer risk (OR=1.17).
• Total testosterone (TT) was suggestively associated with a reduced risk of stomach cancer (OR=0.66) and pancreatic cancer (OR=0.59).
• A suggestive association was also noted between TT and small intestine cancer risk.

Conclusions:

• Testosterone's role in cancer development is specific, with a notable association with prostate cancer risk.
• The study provides insights into the potential protective effects of total testosterone against stomach and pancreatic cancers.
• No significant causal associations were found between testosterone and other investigated cancers in men.