Open Access Research article

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

Anna Abulí12, Ceres Fernández-Rozadilla3, Virginia Alonso-Espinaco1, Jenifer Muñoz1, Victoria Gonzalo1, Xavier Bessa2, Dolors González4, Joan Clofent5, Joaquin Cubiella6, Juan D Morillas7, Joaquim Rigau8, Mercedes Latorre9, Fernando Fernández-Bañares10, Elena Peña11, Sabino Riestra12, Artemio Payá13, Rodrigo Jover13, Rosa M Xicola14, Xavier Llor14, Luis Carvajal-Carmona15, Cristina M Villanueva16, Victor Moreno17, Josep M Piqué1, Angel Carracedo3, Antoni Castells1, Montserrat Andreu2, Clara Ruiz-Ponte3, Sergi Castellví-Bel1* and for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association18

Author Affiliations

1 Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, University of Barcelona, Barcelona, Catalonia, Spain

2 Gastroenterology Department, Parc de Salut Mar, Institut Municipal d'Investigació Mèdica (IMIM), Pompeu Fabra University, Barcelona, Catalonia, Spain

3 Galician Public Foundation of Genomic Medicine, CIBERER, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain

4 Hospital Sant Pau, Barcelona, Catalonia, Spain

5 Department of Gastroenterology, Hospital Meixoeiro, Vigo, Spain

6 Department of Gastroenterology, Hospital de Ourense, Galicia, Spain

7 Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain

8 Department of Medicine, Hospital General de Granollers, Barcelona, Catalonia, Spain

9 Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain

10 Department of Gastroenterology, Hospital Mutua de Terrassa, Barcelona, Catalonia, Spain

11 Department of Gastroenterology, Hospital Royo Villanova, Zaragoza, Spain

12 Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Asturias, Spain

13 Department of Pathology and Gastroenterology, Hospital General d'Alacant, Alicante, Spain

14 Section of Digestive Diseases and Nutrition and Cancer Center, University of Illinois at Chicago, IL 60612, USA

15 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK

16 Centre for Research in Environmental Epidemiology (CREAL), IMIM (Hospital del Mar Research Institute). CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

17 IDIBELL-Institut Català d'Oncologia (ICO), CIBER Epidemiología y Salud Pública (CIBERESP), University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain

18 All authors are listed in the Acknowledgements section

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BMC Cancer 2011, 11:339  doi:10.1186/1471-2407-11-339

Published: 5 August 2011



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.


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.


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).


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.

Colorectal Neoplasms; Genetic Predisposition to Disease; Single Nucleotide Polymorphism; Mucins; Genetic Association Studies