Dataset Information

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

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.

SUBMITTER: Hua X

PROVIDER: S-EPMC8254760 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Hua Xinwei X Dai James Y JY Lindström Sara S Harrison Tabitha A TA Lin Yi Y Alberts Steven R SR Alwers Elizabeth E Berndt Sonja I SI Brenner Hermann H Buchanan Daniel D DD Campbell Peter T PT Casey Graham G Chang-Claude Jenny J Gallinger Steven S Giles Graham G GG Goldberg Richard M RM Gunter Marc J MJ Hoffmeister Michael M Jenkins Mark A MA Joshi Amit D AD Ma Wenjie W Milne Roger L RL Murphy Neil N Pai Rish K RK Sakoda Lori C LC Schoen Robert E RE Shi Qian Q Slattery Martha L ML Song Mingyang M White Emily E Marchand Loic Le LL Chan Andrew T AT Peters Ulrike U Newcomb Polly A PA

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20210510 7

<h4>Background</h4>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.<h4>Methods</h4>We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry f ...[more]

PMID: 33972368

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Dataset Information

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

Background

Methods

Results

Conclusions

Impact

Publications

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

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