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Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study

Authors :
Hua, X
Dai, JY
Lindstrom, S
Harrison, TA
Lin, Y
Alberts, SR
Alwers, E
Berndt, S
Brenner, H
Buchanan, DD
Campbell, PT
Casey, G
Chang-Claude, J
Gallinger, S
Giles, GG
Goldberg, RM
Gunter, MJ
Hoffmeister, M
Jenkins, MA
Joshi, AD
Ma, W
Milne, RL
Murphy, N
Pai, RK
Sakoda, LC
Schoen, RE
Shi, Q
Slattery, ML
Song, M
White, E
Le Marchand, L
Chan, AT
Peters, U
Newcomb, PA
Hua, X
Dai, JY
Lindstrom, S
Harrison, TA
Lin, Y
Alberts, SR
Alwers, E
Berndt, S
Brenner, H
Buchanan, DD
Campbell, PT
Casey, G
Chang-Claude, J
Gallinger, S
Giles, GG
Goldberg, RM
Gunter, MJ
Hoffmeister, M
Jenkins, MA
Joshi, AD
Ma, W
Milne, RL
Murphy, N
Pai, RK
Sakoda, LC
Schoen, RE
Shi, Q
Slattery, ML
Song, M
White, E
Le Marchand, L
Chan, AT
Peters, U
Newcomb, PA
Publication Year :
2021

Abstract

BACKGROUND: A positive association between circulating C-reactive protein (CRP) and colorectal cancer 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 colorectal cancer-specific survival. METHODS: We used individual-level data for 16,918 eligible colorectal cancer 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. Because of 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 colorectal cancer-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 colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-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 colorectal cancer-specific survival. IMPACT: Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1340017211
Document Type :
Electronic Resource