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.

Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting

“…In agreement with results for genetic prediction of CRC with a limited number of SNPs, weighting of risk alleles did not lead to improvement of predictive performance of the GRS, compared to a GRS based on simple counts of risk alleles.…”

“…The prediction from the joint score increased the AUC to 0.636. This AUC estimate is similar to AUCs reported from comprehensive large case–control and cohort studies on CRC risk, which combined environmental risk factors and SNPs, such as the Spanish population study with 21 SNPs and AUC = 0.63 and the study on multiple populations with 63 SNPs and AUC = 0.63 …”

“…This is in agreement with expectations, as the predictive performance of risk scores tested in independent and external samples is generally lower than in the sample used for model development. The prediction from the single GRS (AUC = 0.606) is within the range reported from large case–control studies on CRC risk, while using different set and number of SNPs (e.g., study on multiple populations mainly of north European descent, 10 SNPs, AUC = 0.57; multiple populations of European descent, 27 SNPs, AUC = 0.60; Spanish population, 21 SNPs, AUC = 0.56; multiple populations, 63 SNPs, AUC = 0.60). The prediction from the joint score increased the AUC to 0.636.…”

“…A limited number of independent SNPs was selected, whose incorporation in risk assessment within screening programs might be feasible and practical. Moreover, large studies with distinct number of SNPs have shown comparable performance between the derived polygenic scores . Despite the overall moderate sample size, sample size limitations allowed to assess only two genetic risk groups for the joint risk score.…”

“…[18][19][20][21] Recent studies have demonstrated that combination of environmental and genetic factors may substantially improve prediction of CRC risk. [22][23][24][25] However, to the best of our knowledge, no previous study has combined information from environmental risk scores (ERS) and genetic risk scores (GRS) for predicting the presence of CRC and its precursors, the targets for CRC screening, in a true screening setting.…”