TY - JOUR
T1 - Genetically predicted circulating c-reactive protein concentration and colorectal cancer survival
T2 - A mendelian randomization consortium study
AU - Hua, Xinwei
AU - Dai, James Y.
AU - Lindstrom, Sara
AU - Harrison, Tabitha A.
AU - Lin, Yi
AU - Alberts, Steven R.
AU - Alwers, Elizabeth
AU - Berndt, Sonja I.
AU - Brenner, Hermann
AU - Buchanan, Daniel D.
AU - Campbell, Peter T.
AU - Casey, Graham
AU - Chang-Claude, Jenny
AU - Gallinger, Steven
AU - Giles, Graham G.
AU - Goldberg, Richard M.
AU - Gunter, Marc J.
AU - Hoffmeister, Michael
AU - Jenkins, Mark A.
AU - Joshi, Amit D.
AU - Ma, Wenjie
AU - Milne, Roger L.
AU - Murphy, Neil
AU - Pai, Rish K.
AU - Sakoda, Lori C.
AU - Schoen, Robert E.
AU - Shi, Qian
AU - Slattery, Martha L.
AU - Song, Mingyang
AU - White, Emily
AU - Le Marchand, Loic
AU - Chan, Andrew T.
AU - Peters, Ulrike
AU - Newcomb, Polly A.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research Inc.. All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Background: A positive association between circulating Creactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality.Weused 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. Wecalculated 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.
AB - Background: A positive association between circulating Creactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality.Weused 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. Wecalculated 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.
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U2 - 10.1158/1055-9965.EPI-20-1848
DO - 10.1158/1055-9965.EPI-20-1848
M3 - Article
C2 - 33972368
AN - SCOPUS:85109076361
SN - 1055-9965
VL - 30
SP - 1349
EP - 1358
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -