Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset

Sci Rep. 2017 Jan 13:7:40644. doi: 10.1038/srep40644.

Abstract

Common genetic risk variants for colorectal cancer (CRC) have been identified at approximately 40 loci by genome-wide association studies (GWAS). We investigated the association of these risk variants by age at onset of CRC using case-only and case-control analysis. A total of 1,962 CRC cases and 2,668 controls from two independent case-control studies conducted by Korea's National Cancer Center were included in this study. We genotyped 33 GWAS-identified single-nucleotide polymorphisms (SNPs) associated with CRC risk. The risk allele in SNP rs704017, located at 10q22.3 in the ZMIZ1-AS1 gene, was consistently less frequent among CRC patients aged <50 years than among CRC patients aged ≥50 years in the case-only analysis (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.66-0.92, P = 2.7 × 10-3, in an additive model), although this did not surpass the threshold for multiple testing. The direction of associations between rs704017 and CRC risk differed by age group in the combined case-control analysis (<50 years: OR = 0.77, 95% CI = 0.60-0.98, P = 0.03 and ≥50 years: OR = 1.13, 95% CI = 0.98-1.29, P = 0.09, in a dominant model); the p-values for heterogeneity (Pheterogeneity = 7.5 × 10-3) and for interaction were statistically significant (Pinteraction = 7.8 × 10-3, in the dominant model). Our results suggest that the CRC susceptibility SNP rs704017 has a hereditary effect on onset age of CRC.

Publication types

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

MeSH terms

  • Age of Onset
  • Aged
  • Alleles
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors