Abstract
The association between polycystic ovary syndrome (PCOS) and endometrial cancer remains unclear. We aimed to investigate the causal association between genetically predicted PCOS and endometrial cancer risk in two ethnic groups through a two-sample Mendelian randomization (MR) approach. Our study includes 13 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for PCOS in Europeans, and another 13 SNPs are used as IVs for PCOS in Asians. Outcome data were obtained from the largest published meta-GWAS of European ancestry to date, as well as from the BioBank Japan Project of Asian ancestry. Our study demonstrates that genetically predicted PCOS is not causally associated with the risk of overall endometrial cancer in either Europeans or Asians (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.85–1.01, p = 0.09 and OR = 0.98, 95% CI 0.84–1.13, p = 0.75, respectively). Subgroup analyses according to histotype further illustrate that PCOS might not be associated with the risk of either endometrioid endometrial cancer or non-endometrioid endometrial cancer in European ancestry. No pleiotropy is found in our study, and a sensitivity analysis shows similar results. Our results indicate that genetically predicted PCOS might not be associated with the risk of endometrial cancer.
Highlights
Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive endocrine disorders affecting five to 10 percent of reproductive-aged women around the world, and it greatly influences patient quality of life, fertility and long-term health [1, 2]
Among individuals of European ancestry, we found that rs2271194 was significantly associated with body mass index (BMI), whereas in Asian PCOS single nucleotide polymorphisms (SNPs), we found that rs705702 was correlated with BMI
We did not observe a significant association between genetically predicted PCOS and the risk of endometrial cancer in either European ancestry or Asian ancestry (OR = 0.93, 95% confidence intervals (CIs) 0.85–1.01, p = 0.09 and Odds ratios (OR) = 0.98, 95% CI 0.84–1.13, p = 0.75, respectively)
Summary
Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive endocrine disorders affecting five to 10 percent of reproductive-aged women around the world, and it greatly influences patient quality of life, fertility and long-term health [1, 2]. PCOS is an unexplained heterogeneous clinical syndrome that might be caused by a combination of genetic and environmental factors. Women with PCOS are at higher risk for comorbidities, including obesity, hyperinsulinemia, insulin resistance (IR), metabolic disorders, infertility, endothelial dysfunction, cardiovascular disorders and the development of cancer. Previous studies have found that PCOS was associated with an increased risk of cancer in the endometrium, ovaries, endocrine glands, pancreas, kidneys and skeletal and hematopoietic system [7, 8]
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