title: Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset.
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.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea.|Molecular Epidemiology Branch, National Cancer Center, Goyang, 10408, Korea.
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.|Department of Surgery, Seoul National University College of Medicine and Hospital, Seoul, 03080, Korea.|Center for Colorectal Cancer, National Cancer Center, Goyang, 10408, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, 10408, Korea.
authors.forename: Jeongseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for Colorectal Cancer, National Cancer Center, Goyang, 10408, Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors