Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry
Jiang, Xuejuan; Esteban Castelao, J.; Vandenberg, David; Carracedo, Angel; Redondo, Carmen M.; Conti, David V.; Paredes Cotore, Jesus P.; Potter, John D.; Newcomb, Polly A.; Passarelli, Michael N.; Jenkins, Mark A.; Hopper, John L.; Gallinger, Steven; Le Marchand, Loic; Martinez, Maria E.; Ahnen, Dennis J.; Baron, John A.; Lindor, Noralane M.; Haile, Robert W.; Gago Dominguez, Manuela
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Identificadores
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Fecha de publicación
2013Título de revista
PLoS One
Tipo de contenido
Artigo
DeCS
Antiinflamatorios no Esteroideos | Neoplasias Colorrectales | Predisposición Genética a la Enfermedad | Polimorfismo de Nucleótido Simple | Proteína smad7 | Modelos LogísticosMeSH
Adult | Aged | Anti-Inflammatory Agents, Non-Steroidal | Body Mass Index | Case-Control Studies | Colonic Polyps | Colorectal Neoplasms | Female | Genetic Predisposition to Disease | Humans | Logistic Models | Middle Aged | Odds Ratio | Polymorphism, Single Nucleotide | Registries | Risk | Smad7 Protein | SmokingResumen
BACKGROUND: Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. MATERIALS AND METHODS: 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. RESULTS: Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. CONCLUSIONS: SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs.
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