Body Mass Index and Causal Relationships with Four Characteristic Female Cancers: A Two-Sample Mendelian Randomization Study

Yulai YIN; Xiaoyu ZHANG

doi:10.5281/zenodo.11079951

Authors

YIN Yulai Hebei Medical University Author
ZHANG Xiaoyu Cangzhou Central Hospital Author

DOI:

https://doi.org/10.5281/zenodo.11079951

Keywords:

Mendelian Randomisation, Body Mass Index, breast cancer, endometrial cancer, ovarian cancer, cervical cancer

Abstract

This study employs a two-sample Mendelian randomization (MR) approach to investigate the causal relationship between increased Body Mass Index (BMI) and four characteristic female cancers. BMI and data pertaining to the four characteristic female cancers were obtained from the GWAS database. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) based on assumptions. The PhenoScanner method was utilized to eliminate SNPs associated with confounding factors. Five Mendelian randomization analysis methods, including inverse variance-weighted (IVW), were employed for two-sample Mendelian randomization analysis. Cochran Q and Rücker Q heterogeneity tests were conducted using IVW and MR-Egger methods. Egger-intercept method was employed for pleiotropy testing, and stepwise exclusion testing for sensitivity analysis. F-values were calculated to assess the presence of weak IVs bias. Genetically predicted increase in BMI was causally associated with reduced risk of breast cancer (OR=0.648, 95% CI: 0.535-0.783, P=7.74e-06), and increased risk of endometrial cancer (OR=1.534, 95% CI: 1.195-1.970, P=7.84e-04). There was insufficient evidence to suggest a causal relationship between genetically determined BMI increase and other characteristic female cancers studied. Increased Body Mass Index may potentially decrease the risk of female breast cancer while increasing the risk of endometrial cancer. There is inadequate evidence to indicate a significant impact of increased BMI on the occurrence risk of other characteristic female cancers studied. Further research is warranted to elucidate these findings.

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