Circulating inflammatory markers and risk of endometrial cancer: A systematic review and meta-analysis

Evidence suggests that inflammation may be associated with a higher risk of endometrial cancer, but previous reviews have typically examined a limited number of biomarkers. This study aimed to critically appraise the evidence on the effect of 13 circulating inflammatory biomarkers on endometrial cancer risk. MEDLINE and EMBASE databases were searched for prospective cohort, (nested) case-control and case-cohort studies, and Mendelian randomization (MR) studies published up to 31 March 2023. We performed a random-effects meta-analysis to estimate the pooled risk ratio and 95 % confidence interval (CI) for the association between each biomarker and endometrial cancer risk. Heterogeneity between studies was assessed using the I-2 statistic. Eight studies were included in the meta-analysis. Comparing groups with the highest versus lowest concentration of biomarker, adiponectin levels were inversely associated with risk of endometrial cancer (risk ratio (RR) =0.75, 95 % CI: 0.57-0.99, I2: 9 %). Higher levels of CRP (RR=1.18, 95 % CI: 1.05-1.33, I-2: 2 %) and TNF-alpha (RR=1.58, 95 % CI: 1.13-2.21, I-2: 0 %) were positively associated with risk of endometrial cancer. There was suggestive evidence for a positive association was also found for IL-6 (RR=1.29, 95 % CI: 0.88-1.88, I-2: 0 %) and leptin (RR=1.50, 95 % CI: 0.83-2.71, I-2: 0 %). Our findings suggest that circulating inflammatory biomarkers are likely involved in the carcinogenesis of endometrial cancer. Future studies should consider prospective or MR design and measure a wider range of inflammatory markers.