No Link Found Between PCOS, Endometrial Cancer

A new analysis of 13 single nucleotide polymorphisms (SNPs) as instrumental variables did not show a pleitropic relationship between polycystic ovary syndrome (PCOS) and endometrial cancer, the incidence and mortality of which are rising, according to study findings published in Frontiers in Endocrinology.

“PCOS is an unexplained heterogeneous clinical syndrome that might be caused by a combination of genetic and environmental factors,” the authors wrote. “We aimed to investigate the causal association between genetically predicted PCOS and endometrial cancer risk in 2 ethnic groups through a 2-sample Mendelian randomization approach.”

They used data on patients of European ancestry from the largest genome-wide association study (GWAS) of endometrial cancer (n = 12,906 persons with endometrial cancer and 108,979 health controls; 17 studies from the UK Biobank, the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium) and data on patients of Asian descent from the BioBank Japan Project (n = 999 cases of endometrial cancer and 89,731 controls) to estimate if there was a link between PCOS and risk of endometrial cancer.

Their overall analysis results do not show significant associations between women with genetically predicted PCOS and them having a higher risk of endometrial cancer. Findings were nearly equal between the groups:

• Women of European ancestry had an odds ratio (OR) of 0.93 (95% CI, 0.85-1.01; P = .09)
• Women of Asian ancestry had an OR of 0.98 (95% CI, 0.84-1.13; P = 0.75)

A subgroup analysis according to histotype showed similar results, in that having PCOC was not linked to higher risks of either endometrioid endometrial cancer or nonendometrioid endometrial cancer among the women with European ancestry:

• Endometrioid endometrial cancer had an OR of 0.96 (95% CI, 0.87-1.05; P = .36)
• Nonendometrioid endometrial cancer had an OR of 0.99 (95% CI, 0.79-1.25; P = 0.94)

Knowing that significant correlations exist between endometrial cancer and obesity, high body mass index (BMI), and waist-to-hip ratio (WHR)—which increase a women’s risk of PCOS—the authors conducted a separate analysis of these confounders.

After excluding the PCOS SNPs associated with WHR, the risk for endometrial cancer dropped only among the participants of European ancestry (OR, 0.91; 95% CI, 0.84-0.99; P = .03), while excluding the PCOS SNPs associated with BMI did not show a similar relationship between the Asian or European patients. In addition, excluding the PCOS SNPs associated with either BMI or WHR showed a lower risk of endometrial cancer in Europeans only (OR, 0.91; 95% CI, 0.83-0.99; P = .03).

Noting that previous findings on the risk of endometrial cancer from PCO are controversial, because of confounding factors, the authors note that their findings are significant because their use of a Mendelian randomization (MR) approach “can control for the influence of confounding factors.” In addition, their use of a 2-sample MR design, the incorporation of instrumental variables from the latest PCOS GWAS among Asians and Europeans, and utilizing sensitivity analyses for confounding factors and pleitrophy add heft to their findings.

“Moreover, we stratified our outcomes based on the histotype of endometrial cancer, which was often neglected by previous observation studies,” they added. “In conclusion, based on the MR results generated using data summaries from large-scale GWAS analyses, our observations suggest that genetically predicted PCOS is not related to a higher risk of endometrial cancer.”

Reference

Chen H, Zhang Y, Li S, et al. The genetic association of polycystic ovary syndrome and the risk of endometrial cancer: a Mendelian randomization study. Front Endocrinol (Lausanne). Published online November 5, 2021. doi:10.3389/fendo.2021.756137