Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

Konstantinos K. Tsilidis, Kathy J. Helzlsouer, Michael W. Smith, Victoriya Grinberg, Judith Hoffman-Bolton, Sandra L. Clipp, Kala Visvanathan, Elizabeth A. Platz

Research output: Contribution to journalArticle

Abstract

Objective and methods: The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results: Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions: Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1739-1751
Number of pages13
JournalCancer Causes and Control
Volume20
Issue number9
DOIs
StatePublished - Nov 1 2009

Keywords

  • Colorectal cancer
  • Genetic epidemiology
  • Inflammation
  • Obesity
  • Prospective study

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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