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

About this Publication
Title
Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study.
Pubmed ID
33972368 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Epidemiol Biomarkers Prev. 2021 Jul; Volume 30 (Issue 7): Pages 1349-1358
Authors
Hua X, Dai JY, Lindström S, Harrison TA, Lin Y, Alberts SR, Alwers E, Berndt SI, 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, ...show more Ma W, Milne RL, Murphy N, Pai RK, Sakoda LC, Schoen RE, Shi Q, Slattery ML, Song M, White E, Marchand LL, Chan AT, Peters U, Newcomb PA
Affiliations
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Department of Clinical Pathology, Colorectal Oncogenomics Group, The University of Melbourne, Parkville, Victoria, Australia.
  • Department of Population Science, American Cancer Society, Atlanta, Geogia.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
...show more
  • West Virginia University Cancer Institute, Morgantown, West Virginia.
  • Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Center for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
  • Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. pnewcomb@fredhutch.org.
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.

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