Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype

被引：48

作者：

Abuli, Anna ^{[1
]}

Bessa, Xavier ^{[1
]}

Ramon Gonzalez, Juan ^{[2
]}

Ruiz-Ponte, Clara ^{[3
]}

Caceres, Alejandro ^{[2
]}

Munoz, Jenifer ^{[4
]}

Gonzalo, Victoria ^{[4
]}

Balaguer, Francesc ^{[4
]}

Fernandez-Rozadilla, Ceres

Gonzalez, Dolors ^{[5
]}

de Castro, Luisa ^{[6
]}

Clofent, Juan ^{[6
]}

Bujanda, Luis ^{[7
]}

Cubiella, Joaquin ^{[8
]}

Ma Rene, Josep ^{[9
]}

Diego Morillas, Juan ^{[10
]}

Lanas, Angel ^{[11
]}

Rigau, Joaquim ^{[12
]}

Ma Garcia, Ana ^{[13
]}

Latorre, Mercedes ^{[14
]}

Salo, Joan ^{[15
]}

Fernandez Banares, Fernando ^{[16
]}

Argueello, Lidia ^{[17
]}

Pena, Elena ^{[18
]}

Vilella, Angels ^{[19
]}

Riestra, Sabino ^{[20
]}

Carreno, Ramiro ^{[21
]}

Paya, Artemio ^{[22
]}

Alenda, Cristina ^{[22
]}

Xicola, Rosa M. ^{[23
]}

Doyle, Brian J. ^{[23
]}

Jover, Rodrigo ^{[22
]}

Llor, Xavier ^{[23
]}

Carracedo, Angel ^{[3
]}

Castells, Antoni ^{[4
]}

Castellvi-Bel, Sergi ^{[4
]}

Andreu, Montserrat ^{[1
]}

机构：

[1] Pompeu Fabra Univ, Hosp Mar, Inst Municipal Invest Med, Dept Gastroenterol, Barcelona, Catalonia, Spain

[2] Inst Municipal Invest Med, Ctr Res Environm Epidemiol, E-08003 Barcelona, Catalonia, Spain

[3] Univ Santiago de Compostela, Genom Med Grp, CIBERER, Fdn Publ Galega Med Xen, Santiago De Compostela, Galicia, Spain

[4] Univ Barcelona, IDIBAPS, CIBERehd, Dept Gastroenterol,Hosp Clin, E-08036 Barcelona, Catalonia, Spain

[5] Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Catalonia, Spain

[6] Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain

[7] Univ Basque Country, CIBERehd, Hosp Donostia, Dept Gastroenterol, San Sebastian, Spain

[8] Hosp Ourense, Dept Gastroenterol, Galicia, Spain

[9] Hosp Arnau Vilanova, Dept Gastroenterol, Lleida, Catalonia, Spain

[10] Hosp 12 Octubre, Dept Gastroenterol, E-28041 Madrid, Spain

[11] Hosp Clin Univ, CIBERehd, Dept Gastroenterol, Zaragoza, Spain

[12] Hosp Gen Granollers, Dept Med, Barcelona, Catalonia, Spain

[13] Fdn Formac & Invest Sanitaria, Murcia, Spain

[14] Hosp Gen Univ Valencia, Dept Gastroenterol, Valencia, Spain

[15] Hosp Gen Vic, Dept Gastroenterol, Barcelona, Catalonia, Spain

[16] Hosp Mutua Terrassa, Dept Gastroenterol, Barcelona, Catalonia, Spain

[17] Hosp Univ La Fe, Dept Gastroenterol, Valencia, Spain

[18] Hosp Royo Villanova, Dept Gastroenterol, Zaragoza, Spain

[19] Hosp Son Llatzer, Dept Med, Palma de Mallorca, Balearic Isl, Spain

[20] Univ Oviedo, Hosp Cent Asturias, Dept Gastroenterol, E-33080 Oviedo, Asturias, Spain

[21] Fdn Hosp Calahorra, Dept Gastroenterol, Navarra, Spain

[22] Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain

[23] Univ Illinois, Digest Dis & Nutr Sect, Chicago, IL USA

来源：

GASTROENTEROLOGY | 2010年 / 139卷 / 03期

关键词：

Colon Cancer; Genetic Susceptibility; Low Penetrance; Genotype-Phenotype Correlation; GENOME-WIDE ASSOCIATION; CHROMOSOME; 8Q24; LYNCH SYNDROME; COLON-CANCER; LOCI; RS6983267; 18Q21; SCAN; IDENTIFICATION; POLYMORPHISM;

D O I：

10.1053/j.gastro.2010.05.072

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：788 / U129

页数：15

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