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

BMC Cancer

Anna Abulí⁵  Ceres Fernández-Rozadilla⁷  Virginia Alonso-Espinaco⁸  Jenifer Muñoz⁸  Victoria Gonzalo⁸  Xavier Bessa⁵  Dolors González¹  Joan Clofent¹⁴  Joaquin Cubiella¹⁶  Juan D Morillas¹⁷  Joaquim Rigau¹⁵  Mercedes Latorre⁴  Fernando Fernández-Bañares¹⁰  Elena Peña¹³  Sabino Riestra³  Artemio Payá⁶  Rodrigo Jover⁶  Rosa M Xicola⁹  Xavier Llor⁹  Luis Carvajal-Carmona²  Cristina M Villanueva¹²  Victor Moreno¹⁸  Josep M Piqué⁸  Angel Carracedo⁷  Antoni Castells⁸  Montserrat Andreu⁵  Clara Ruiz-Ponte⁷  Sergi Castellví-Bel⁸  for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association¹¹ 

[1] Hospital Sant Pau, Barcelona, Catalonia, Spain

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

[3] Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Asturias, Spain

[4] Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain

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

[6] Department of Pathology and Gastroenterology, Hospital General d'Alacant, Alicante, Spain

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

[8] Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, University of Barcelona, Barcelona, Catalonia, Spain

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

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

[11] All authors are listed in the Acknowledgements section

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

[13] Department of Gastroenterology, Hospital Royo Villanova, Zaragoza, Spain

[14] Department of Gastroenterology, Hospital Meixoeiro, Vigo, Spain

[15] Department of Medicine, Hospital General de Granollers, Barcelona, Catalonia, Spain

[16] Department of Gastroenterology, Hospital de Ourense, Galicia, Spain

[17] Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain

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

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

Others  :  1080796
DOI  :  10.1186/1471-2407-11-339

 received in 2011-02-22, accepted in 2011-08-05,  发布年份 2011

【 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.

【 授权许可】

   
2011 Abulí et al; licensee BioMed Central Ltd.

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