Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins
Por:
Abuli, A, Fernandez-Rozadilla, C, Alonso-Espinaco, V, Munoz, J, Gonzalo, V, Bessa, X, Gonzalez, D, Clofent, J, Cubiella, J, Morillas, JD, Rigau, J, Latorre, M, Fernandez-Banares, F, Pena, E, Riestra, S, Paya, A, Jover, R, Xicola, RM, Llor, X, Carvajal-Carmona, L, Villanueva, CM, Moreno, V, Pique, JM, Carracedo, A, Castells, A, Andreu, M, Ruiz-Ponte, C, Castellvi-Bel, S
Publicada:
5 ago 2011
Resumen:
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.
Filiaciones:
Abuli, A:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Pompeu Fabra Univ, IMIM, Dept Gastroenterol, Barcelona, Catalonia, Spain
Fernandez-Rozadilla, C:
Univ Santiago Compostela, Hosp Clin, Genom Med Grp, CIBERER,Galician Publ Fdn Genom Med, Galicia, Spain
Alonso-Espinaco, V:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Munoz, J:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Gonzalo, V:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Bessa, X:
Pompeu Fabra Univ, IMIM, Dept Gastroenterol, Barcelona, Catalonia, Spain
Gonzalez, D:
Hosp Santa Creu & Sant Pau, Barcelona, Catalonia, Spain
Clofent, J:
Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
Cubiella, J:
Hosp Ourense, Dept Gastroenterol, Galicia, Spain
Morillas, JD:
Hosp 12 Octubre, Dept Gastroenterol, E-28041 Madrid, Spain
Rigau, J:
Hosp Gen Granollers, Dept Med, Barcelona, Catalonia, Spain
Latorre, M:
Univ Valencia, Gen Hosp, Dept Gastroenterol, Valencia, Spain
Fernandez-Banares, F:
Hosp Mutua de Terrassa, Dept Gastroenterol, Barcelona, Catalonia, Spain
Pena, E:
Hosp Royo Villanova, Dept Gastroenterol, Zaragoza, Spain
Riestra, S:
Univ Oviedo, Hosp Cent Asturias, Dept Gastroenterol, E-33080 Oviedo, Asturias, Spain
Paya, A:
Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
Jover, R:
Hosp Gen Alacant, Dept Pathol & Gastroenterol, Alicante, Spain
Xicola, RM:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL 60612 USA
Univ Illinois, Ctr Canc, Chicago, IL 60612 USA
Llor, X:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL 60612 USA
Univ Illinois, Ctr Canc, Chicago, IL 60612 USA
Carvajal-Carmona, L:
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
Villanueva, CM:
Hosp Mar Res Inst, CIBERESP, IMIM, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain
Moreno, V:
Univ Barcelona, CIBERESP, IDIBELL Inst Catala Oncol ICO, Barcelona, Spain
Pique, JM:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Carracedo, A:
Univ Santiago Compostela, Hosp Clin, Genom Med Grp, CIBERER,Galician Publ Fdn Genom Med, Galicia, Spain
Castells, A:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Andreu, M:
Pompeu Fabra Univ, IMIM, Dept Gastroenterol, Barcelona, Catalonia, Spain
Ruiz-Ponte, C:
Univ Santiago Compostela, Hosp Clin, Genom Med Grp, CIBERER,Galician Publ Fdn Genom Med, Galicia, Spain
Castellvi-Bel, S:
Univ Barcelona, CIBERehd, Hosp Clin, Dept Gastroenterol,IDIBAPS, Barcelona, Catalonia, Spain
Gold, Green Published
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