Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study

Cancer Causes Control. 2013 Dec;24(12):2077-87. doi: 10.1007/s10552-013-0285-y. Epub 2013 Sep 14.

Abstract

Purpose: Many studies, including the Atherosclerosis Risk in Communities (ARIC) cohort, reported a positive association between plasma C-reactive protein (CRP)-a biomarker of low-grade chronic inflammation-and colorectal cancer risk, although it is unclear whether the association is causal. Our aims were to assess the associations of a CRP genetic risk score (CRP-GRS) created from single-nucleotide polymorphisms (SNPs) with colorectal cancer risk, as well as examine plasma CRP and CRP-GRS in relation to common cancers in the ARIC cohort.

Methods: Cox proportional hazards models were used to prospectively estimate hazard ratios (HRs) and 95 % confidence interval (95 % CI) of total, colorectal, lung, prostate, and breast cancers in relation to: (1) CRP-GRS among 8,657 Whites followed in 1987-2006 and (2) log-transformed plasma CRP among 7,603 Whites followed in 1996-2006. A weighted CRP-GRS was comprised of 20 CRP-related SNPs located in/near CRP, APOC1, HNF1A, LEPR, and 16 other genes that were identified in genome-wide association studies.

Results: After multivariable adjustment, one standard deviation increment of the CRP-GRS was associated with colorectal cancer risk (HR 1.19; 95 % CI 1.03-1.37), but not with any other cancer. One unit of log-transformed plasma CRP was associated with the risk of total, colorectal, lung, and breast cancers: HRs (95 % CIs) were 1.08 (1.01-1.15), 1.24 (1.01-1.51), 1.29 (1.08-1.54), and 1.27 (1.07-1.51), respectively. HRs remained elevated, although lost statistical significance for all but breast cancer, after excluding subjects with <2 years of follow-up.

Conclusions: The study corroborates a causative role of chronic low-grade inflammation in colorectal carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • African Americans / genetics*
  • Atherosclerosis / blood
  • Atherosclerosis / complications*
  • Atherosclerosis / genetics
  • Biomarkers, Tumor / analysis*
  • C-Reactive Protein / metabolism*
  • DNA, Neoplasm / genetics
  • European Continental Ancestry Group / genetics*
  • Female
  • Follow-Up Studies
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / etiology*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Prospective Studies
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • C-Reactive Protein

Grant support