Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study

Gemma Ibáñez-Sanz, Anna Díez-Villanueva, M. Henar Alonso, Francisco Rodríguez-Moranta, Beatriz Pérez-Gómez, Mariona Bustamante, Vicente Martin, Javier Llorca, Pilar Amiano, Eva Ardanaz, Adonina Tardón, Jose J. Jiménez-Moleón, Rosana Peiró, Juan Alguacil, Carmen Navarro, Elisabet Guinó, Gemma Binefa, Pablo Fernández-Navarro, Anna Espinosa, Verónica Dávila-Batista, Antonio José Molina, Camilo Palazuelos, Gemma Castaño-Vinyals, Nuria Aragonés, Manolis Kogevinas, Marina Pollán, Victor Moreno

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 (5(th) quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1(st) 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.