| Title: | Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study |
| Journal: | Cancer Epidemiology Biomarkers & Prevention |
| Published: | 10 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33972368/ |
| DOI: | https://doi.org/10.1158/1055-9965.epi-20-1848 |
| URL: | https://aacrjournals.org/cebp/article-pdf/30/7/1349/3100874/1349.pdf |
Publication 13787
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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.</p>
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.</p>
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.</p>
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.</p>
IMPACT: Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.</p>
12 Keywords
- Aged
- C-Reactive Protein
- Case-Control Studies
- Colorectal Neoplasms
- Female
- Follow-Up Studies
- Genetic Variation
- Humans
- Male
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Risk Factors
34 Authors
- Xinwei Hua
- James Y. Dai
- Sara Lindström
- Tabitha A. Harrison
- Yi Lin
- Steven R. Alberts
- Elizabeth Alwers
- Sonja I. Berndt
- Hermann Brenner
- Daniel D. Buchanan
- Peter T. Campbell
- Graham Casey
- Jenny Chang-Claude
- Steven Gallinger
- Graham G. Giles
- Richard M. Goldberg
- Marc J. Gunter
- Michael Hoffmeister
- Mark A. Jenkins
- Amit D. Joshi
- Wenjie Ma
- Roger L. Milne
- Neil Murphy
- Rish K. Pai
- Lori C. Sakoda
- Robert E. Schoen
- Qian Shi
- Martha L. Slattery
- Mingyang Song
- Emily White
- Loic Le Marchand
- Andrew T. Chan
- Ulrike Peters
- Polly A. Newcomb
1 Application
| Application ID | Title |
|---|---|
| 8614 | Evaluating genome-wide association and gene-environment interaction in colorectal cancer |
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