Causal effect of C-reaction protein and endometrial cancer: Genetic evidence of the role of inflammation in endometrial cancer

Consensus remains elusive regarding the relationship between C-reactive protein (CRP) levels and endometrial cancer (EC). Our study sought to elucidate the causal association between CRP and EC, aiming to contribute to the understanding of this complex interplay. We primarily utilized the random-effects inverse variance-weighted method. This approach served as the foundation for our analysis, complemented by 3 additional techniques, including Mendelian randomization-Egger, weighted-median, and weighted mode. A series of sensitivity analyses were also conducted to affirm the stability and reliability of our results. Employing the inverse variance-weighted method, our findings indicated that a one-unit increment in log-transformed CRP concentrations (mg/L) was associated with a relatively 9.7% increased risk of overall EC (odds ratio OR = 1.097, 95% confidence interval CI: 0.996-1.208, P = .061), an 11% higher risk of endometrioid endometrial cancer (OR = 1.110, 95% CI: 1.000-1.231, P = .049) and a 25% increased risk of non-endometrioid cancers (OR = 1.250, 95% CI: 1.005-1.555, P = .045). Sensitivity analyses did not reveal evidence of horizontal pleiotropy in the analysis of CRP and overall EC, endometrioid endometrial cancer, or non-endometrioid cancers (P > .05). In the reverse analysis, our data demonstrated that EC exert no reverse effect on CRP levels. Our study suggested causal relationships between CRP and an elevated risk of EC and its subtypes, which contribute to the ongoing discourse on the role of inflammation, as indicated by CRP levels, in the etiology of EC and its variants.