Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype
Por:
Abuli, A, Bessa, X, Gonzalez, JR, Ruiz-Ponte, C, Caceres, A, Munoz, J, Gonzalo, V, Balaguer, F, Fernandez-Rozadilla, C, Gonzalez, D, de Castro, L, Clofent, J, Bujanda, L, Cubiella, J, Rene, JM, Morillas, JD, Lanas, A, Rigau, J, Garcia, AM, Latorre, M, Salo, J, Banares, FF, Arguello, L, Pena, E, Vilella, A, Riestra, S, Carreno, R, Paya, A, Alenda, C, Xicola, RM, Doyle, BJ, Jover, R, Llor, X, Carracedo, A, Castells, A, Castellvi-Bel, S, Andreu, M
Publicada:
1 sep 2010
Resumen:
BACKGROUND & AIMS: Ten common low-penetrant genetic variants have been consistently associated with colorectal cancer (CRC) risk; little is known about the correlation between these variants and CRC phenotype. Characterization of such a correlation would improve CRC management and prevention programs. We assessed the association between these genetic variants and CRC phenotype in patients and modeled pairwise combinations to detect epistasis. METHODS: The validation population corresponded to a prospective, multicenter, population-based cohort (EPICOLON I) of 1096 patients with newly diagnosed CRC. The replication set was an independent, prospective, multicenter Spanish cohort (EPICOLON II) of 895 patients with newly diagnosed CRC. For individual single nucleotide polymorphism (SNP) association analyses, a multivariate method using logistic regression was applied in EPICOLON I and subsequently prospectively validated in EPICOLON II. Interactions between SNPs were assessed using the likelihood ratio test. RESULTS: Validated results confirmed that the C allele on 8q23.3 (rs16892766) was significantly associated with advanced-stage tumors (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.15-1.90; P value = 4.9 x 10(-3)). The G allele on 8q24.21 (rs6983267) was more common in patients with a familial history of CRC (OR, 2.02; 95% CI, 1.35-3.03; P value = 3.9 x 10(-4)). The combination of rs6983267 on 8q24.21 and rs9929218 on 16q22.2 was associated with a history of colorectal adenoma (carriers of GG and AA, respectively; OR, 2.28; 95% CI, 1.32-3.93; P = 5.0 x 10(-4)). CONCLUSIONS: CRC susceptibility variants at 8q23.3, 8q24.21, and 16q22.2 appear to be associated with cancer phenotype. These findings might be used to develop screening and surveillance strategies.
Filiaciones:
Abuli, A:
Pompeu Fabra Univ, Hosp Mar, Inst Municipal Invest Med, Dept Gastroenterol, Barcelona, Catalonia, Spain
Bessa, X:
Pompeu Fabra Univ, Hosp Mar, Inst Municipal Invest Med, Dept Gastroenterol, Barcelona, Catalonia, Spain
Gonzalez, JR:
Inst Municipal Invest Med, Ctr Res Environm Epidemiol, E-08003 Barcelona, Catalonia, Spain
Ruiz-Ponte, C:
Univ Santiago de Compostela, Genom Med Grp, CIBERER, Fdn Publ Galega Med Xen, Santiago De Compostela, Galicia, Spain
Caceres, A:
Inst Municipal Invest Med, Ctr Res Environm Epidemiol, E-08003 Barcelona, Catalonia, Spain
Munoz, J:
Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain
Gonzalo, V:
Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain
Balaguer, F:
Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain
Gonzalez, D:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Catalonia, Spain
de Castro, L:
Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
Clofent, J:
Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
Bujanda, L:
Univ Basque Country, CIBERehd, Hosp Donostia, Dept Gastroenterol, San Sebastian, Spain
Cubiella, J:
Hosp Ourense, Dept Gastroenterol, Galicia, Spain
Rene, JM:
Hosp Arnau Vilanova, Dept Gastroenterol, Lleida, Catalonia, Spain
Morillas, JD:
Hosp 12 Octubre, Dept Gastroenterol, E-28041 Madrid, Spain
Lanas, A:
Hosp Clin Univ, CIBERehd, Dept Gastroenterol, Zaragoza, Spain
Rigau, J:
Hosp Gen Granollers, Dept Med, Barcelona, Catalonia, Spain
Garcia, AM:
Fdn Formac & Invest Sanitaria, Murcia, Spain
Latorre, M:
Hosp Gen Univ Valencia, Dept Gastroenterol, Valencia, Spain
Salo, J:
Hosp Gen Vic, Dept Gastroenterol, Barcelona, Catalonia, Spain
Banares, FF:
Hosp Mutua Terrassa, Dept Gastroenterol, Barcelona, Catalonia, Spain
Arguello, L:
Hosp Univ La Fe, Dept Gastroenterol, Valencia, Spain
Pena, E:
Hosp Royo Villanova, Dept Gastroenterol, Zaragoza, Spain
Vilella, A:
Hosp Son Llatzer, Dept Med, Palma de Mallorca, Balearic Isl, Spain
Riestra, S:
Univ Oviedo, Hosp Cent Asturias, Dept Gastroenterol, E-33080 Oviedo, Asturias, Spain
Carreno, R:
Fdn Hosp Calahorra, Dept Gastroenterol, Navarra, Spain
Paya, A:
Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
Alenda, C:
Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
Xicola, RM:
Univ Illinois, Digest Dis & Nutr Sect, Chicago, IL USA
Doyle, BJ:
Univ Illinois, Digest Dis & Nutr Sect, Chicago, IL USA
Jover, R:
Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
Llor, X:
Univ Illinois, Digest Dis & Nutr Sect, Chicago, IL USA
Carracedo, A:
Univ Santiago de Compostela, Genom Med Grp, CIBERER, Fdn Publ Galega Med Xen, Santiago De Compostela, Galicia, Spain
Castells, A:
Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain
Castellvi-Bel, S:
Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain
Andreu, M:
Pompeu Fabra Univ, Hosp Mar, Inst Municipal Invest Med, Dept Gastroenterol, Barcelona, Catalonia, Spain
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