title: Increased risk of colon cancer associated with a genetic polymorphism of SMAD7.
abstract: Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.38; 95% confidence intervals (CI), 1.13-1.68; P linear trend < 0.01] for the TT genotype compared with the CC genotype, whereas the CC genotype of the rs4939827 SNP was inversely associated with colon cancer (0.77; 95% CI, 0.64-0.93) relative to the TT genotype. There were no significant differences in association for either of these polymorphisms when stratified by age, tumor site, sex, or family history. The odds ratios between SMAD7 and colon cancer among individuals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43-0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20-2.38) for the TT genotype of the rs1295371 polymorphism. This result compares to odds ratios of 0.86 (95% CI, 0.68-1.09) for rs4939827 and 1.22 (95% CI, 0.96-1.56) among individuals who did not use aspirin/nonsteroidal anti-inflammatory drugs. An assessment of SMAD7 genotypes with tumor markers did not reveal any significant differences by KRAS2, TP53, CpG island methylator phenotype, or microsatellite instability status. No significant associations were observed for the rs4464148 SNP or other SNPs evaluated in the SMAD7. These results corroborate the findings of GWAS in colon cancer pointing to SMAD7 and reinforce interest in SNPs in this gene.
authors.affiliation: Departments of Internal Medicine and Pathology, University of Utah School of Medicine, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108, USA. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrick
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Wade
authors.initials: W
authors.lastname: Samowitz
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051906:Smad7 Protein / Q000235:genetics*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein