Do testosterone and sex hormone-binding globulin affect cancer risk? A Mendelian randomization and bioinformatics study

Abstract

Using Mendelian Randomization (MR) and large-scale Genome-Wide Association Study (GWAS) data, this study aimed to investigate the potential causative relationship between testosterone and sex hormone-binding globulin (SHBG) levels and the onset of several cancers, including pathway enrichment analyses of single nucleotide polymorphisms (SNPs) associated with cancer allowed for a comprehensive bioinformatics approach, which offered a deeper biological understanding of these relationships. The results indicated that increased testosterone levels in women were associated with a higher risk of breast and cervical cancers but a lower risk of ovarian cancer. Conversely, increased testosterone was linked to lower stomach cancer risk for men, whereas high SHBG levels were related to decreased risks of breast and prostate cancers. The corresponding genes of the identified SNPs, as revealed by pathway enrichment analysis, were involved in significant metabolic and proliferative pathways. These findings emphasize the need for further research into the biological mechanisms behind these associations, paving the way for potential targeted interventions in preventing and treating these cancers.

Keywords:

• Sex hormone binding globulin
• testosterone
• cancer
• mendelian randomization
• bioinformatical analysis

Acknowledgements

We acknowledge the First Affiliated Hospital of Guangzhou Medical University and State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease for providing access to necessary resources for conducting this study.

Authors’ contributions

Xiwen Liu, Lixuan Lin, Qi Cai and Caichen Li designed the article. Haoxiang Xu participated in editing the code. Ruiqi Zeng and Mingtong Zhang performed data analysis and made the graphs. Xinyi Qiu, Shiqi Chen, Xizhe Zhang and Linchong Huang collated the data results. Xiwen Liu, Lixuan Lin and Qi Cai wrote the first draft of the manuscript. Xiwen Liu, Caichen Li and Haoxiang Xu revised the primary version. Wenhua Liang and Jianxing He revised the final version of the manuscript. All authors contributed to revisions of the manuscript. LXW is the guarantor. All authors approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the China National Science Foundation (Grant No. 82022048 & 81871893), the Key Project of Guangzhou Scientific Research Project (grant No. 201804020030).