Risk model for colorectal cancer in Spanish population using environmental and genetic factors : results from the MCC-Spain study

Abstract

Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), 'Biobanco La Fe' (RD 09 0076/00021) and FISABIO Biobank (RD09 0076/00058), as well as at the Public Health Laboratory of Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank of the University of Oviedo, and the ISCIII Biobank. SNP genotyping services were provided by the Spanish 'Centro Nacional de Genotipado' (CEGEN-ISCIII). We thank all the subjects who participated in the study and all MCC-Spain collaborators. This work was supported by the 'Accion Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds-'a way to build Europe' (grants PI08/1770, PI08/0533, PI08/1359, PI09/00773, PI09/01286, PI09/01903, PI09/02078, PI09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/00613, and PI15/00069). Support was also provided by the Fundacion Marques de Valdecilla (grant API 10/09); the Junta de Castilla y Leon (grant LE22A10-2); the Consejeria de Salud of the Junta de Andalucia (2009-S0143); the Conselleria de Sanitat of the Generalitat Valenciana (grant AP 061/10); the Recercaixa (grant 2010ACUP 00310); the Regional Government of the Basque Country; the Consejeria de Sanidad de la Region de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI (grant 2014SGR647); the Fundacion Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action BM1206 Eucolongene.Departamento de Biología Ambiental y Salud Públic