Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

被引:35
作者
Abuli, Anna [1 ,2 ]
Fernandez-Rozadilla, Ceres [3 ]
Alonso-Espinaco, Virginia [1 ]
Munoz, Jenifer [1 ]
Gonzalo, Victoria [1 ]
Bessa, Xavier [2 ]
Gonzalez, Dolors [4 ]
Clofent, Joan [5 ]
Cubiella, Joaquin [6 ]
Morillas, Juan D. [7 ]
Rigau, Joaquim [8 ]
Latorre, Mercedes [9 ]
Fernandez-Banares, Fernando [10 ]
Pena, Elena [11 ]
Riestra, Sabino [12 ]
Paya, Artemio [13 ]
Jover, Rodrigo [13 ]
Xicola, Rosa M. [14 ,15 ]
Llor, Xavier [14 ,15 ]
Carvajal-Carmona, Luis [16 ]
Villanueva, Cristina M. [17 ]
Moreno, Victor [18 ]
Pique, Josep M. [1 ]
Carracedo, Angel [3 ]
Castells, Antoni [1 ]
Andreu, Montserrat [2 ]
Ruiz-Ponte, Clara [3 ]
Castellvi-Bel, Sergi [1 ]
机构
[1] Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
[2] Pompeu Fabra Univ, IMIM, Dept Gastroenterol, Barcelona, Catalonia, Spain
[3] Univ Santiago Compostela, Hosp Clin, Genom Med Grp, CIBERER,Galician Publ Fdn Genom Med, Galicia, Spain
[4] Hosp Santa Creu & Sant Pau, Barcelona, Catalonia, Spain
[5] Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
[6] Hosp Ourense, Dept Gastroenterol, Galicia, Spain
[7] Hosp 12 Octubre, Dept Gastroenterol, E-28041 Madrid, Spain
[8] Hosp Gen Granollers, Dept Med, Barcelona, Catalonia, Spain
[9] Univ Valencia, Gen Hosp, Dept Gastroenterol, Valencia, Spain
[10] Hosp Mutua de Terrassa, Dept Gastroenterol, Barcelona, Catalonia, Spain
[11] Hosp Royo Villanova, Dept Gastroenterol, Zaragoza, Spain
[12] Univ Oviedo, Hosp Cent Asturias, Dept Gastroenterol, E-33080 Oviedo, Asturias, Spain
[13] Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
[14] Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL 60612 USA
[15] Univ Illinois, Ctr Canc, Chicago, IL 60612 USA
[16] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[17] Hosp Mar Res Inst, CIBERESP, IMIM, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain
[18] Univ Barcelona, CIBERESP, IDIBELL Inst Catala Oncol ICO, Barcelona, Spain
关键词
Colorectal Neoplasms; Genetic Predisposition to Disease; Single Nucleotide Polymorphism; Mucins; Genetic Association Studies; GENOME-WIDE ASSOCIATION; ALCOHOL-CONSUMPTION; VITAMIN-D; RISK; POLYMORPHISMS; COLON; ARLTS1; GAMMA; LOCI;
D O I
10.1186/1471-2407-11-339
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods: CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results: None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, P-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, P-value = 0.09, log-additive 0, 1, 2 alleles). Conclusions: ARL11, ADH1C, GALNTL2 and IL6 genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.
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页数:8
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