C-reactive protein (CRP) is the inflammation-responsible protein and a significant rise of the plasma concentration of CRP is pervasive in the progress of ovarian cancer. However, there are few studies that comprehensively evaluate the correlation between CRP concentrations and ovarian cancer and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted CRP levels and ovarian cancer risk.
Utilizing 32 CRP-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted CRP and ovarian cancer risk using summary statistics from the Ovarian Cancer Association Consortium (25,509 cases and 40,941 controls). The Inverse variance weighted (IVW) method was applied to estimate the causality between genetically elevated CRP concentrations and ovarian cancer risk. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different histotypes of ovarian cancer were also conducted.
An inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and ovarian cancer (OR = 0.93, 95%CI = 0.87-1.00 p = 0.047). When results were examined by histotypes, an inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and endometrioid ovarian cancer (OR = 0.80, 95%CI = 0.70-0.91 p = 0.001), low-grade serous ovarian cancer (OR = 0.70, 95%CI = 0.58-0.86 p = 0.001) and serous ovarian cancer (OR = 0.84, 95%CI = 0.74-0.96 p = 0.012). Additionally, the results demonstrated the absence of the horizontal pleiotropy.
MR findings provide evidence for a causal relationship between genetically predicted one-unit increase in the log-transformed CRP concentrations and reduced ovarian cancer risk, overall and among specific histotypes. Further studies are warranted to investigate the underlying mechanism.