Cancer Epidemiol Biomarkers Prev. 2021 May 10:cebp.1848.2021. doi: 10.1158/1055-9965.EPI-20-1848. Online ahead of print.
ABSTRACT
BACKGROUND: A positive association between circulating C-reactive protein (CRP) and colorectal cancer (CRC) survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically-predicted CRP concentrations and CRC-specific survival.
METHODS: We used individual-level data for 16,918 eligible CRC cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Due to the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically-predicted CRP concentrations and CRC-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components.
RESULTS: Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to CRC. Genetically-predicted CRP concentration was not associated with CRC-specific survival (HD= -1.15, 95% CI: -2.76 to 0.47 per 100,000 person-years, P =0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location.
CONCLUSIONS: Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on CRC-specific survival.
IMPACT: Future research evaluating genetically-determined levels of other circulating inflammatory biomarkers (i.e. interleukin-6) with CRC survival outcomes is needed.
PMID:33972368 | DOI:10.1158/1055-9965.EPI-20-1848