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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Anna Abulí, Ceres Fernández-Rozadilla, Virginia Alonso-Espinaco, Jenifer Muñoz, Victoria Gonzalo, Xavier Bessa, Dolors González, Joan Clofent, Joaquin Cubiella, Juan D Morillas, Joaquim Rigau, Mercedes Latorre, Fernando Fernández-Bañares, Elena Peña, Sabino Riestra, Artemio Payá, Rodrigo Jover, Rosa M Xicola, Xavier Llor, Luis Carvajal-Carmona, Cristina M Villanueva, Victor Moreno, Josep M Piqué, Angel Carracedo, Antoni Castells, Montserrat Andreu, Clara Ruiz-Ponte, Sergi Castellví-Bel, for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association

ABSTRACT

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. More... »

PAGES

339

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-11-339

DOI

http://dx.doi.org/10.1186/1471-2407-11-339

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052704341

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21819567


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452 schema:name Centre for Research in Environmental Epidemiology (CREAL), IMIM (Hospital del Mar Research Institute). CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
453 rdf:type schema:Organization
454 https://www.grid.ac/institutes/grid.5612.0 schema:alternateName Pompeu Fabra University
455 schema:name Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, University of Barcelona, Barcelona, Catalonia, Spain
456 Gastroenterology Department, Parc de Salut Mar, Institut Municipal d'Investigació Mèdica (IMIM), Pompeu Fabra University, Barcelona, Catalonia, Spain
457 rdf:type schema:Organization
458 https://www.grid.ac/institutes/grid.5841.8 schema:alternateName University of Barcelona
459 schema:name IDIBELL-Institut Català d'Oncologia (ICO), CIBER Epidemiología y Salud Pública (CIBERESP), University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
460 rdf:type schema:Organization
 




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