Familial Colorectal Cancer and Genetic Susceptibility: Colorectal Risk Variants in First-Degree Relatives of Patients With Colorectal Cancer

INTRODUCTION: Epidemiological studies estimate that having a first-degree relative (FDR) with colorectal cancer (CRC) increases 2-fold to 3-fold the risk of developing the disease. Because FDRs of CRC patients are more likely to co-inherit CRC risk variants, we aimed to evaluate potential differences in genotype distribution of single nucleotide polymorphisms (SNPs) related to CRC risk between FDRs of patients with nonsyndromic CRC (cases) and individuals with no family history of CRC (controls). METHODS: We designed a case-control study comprising 750 cases and 750 Spanish Caucasian controls matched by sex, age, and histological findings after colonoscopy. Genomic DNA from all participants was genotyped for 88 SNPs associated with CRC risk using the MassArray (Sequenom) platform. RESULTS: Ten of the 88 SNPs analyzed revealed significant associations (P < 0.05) with a family history of CRC in our population. The most robust associations were found for the rs17094983G>A SNP in the long noncoding RNA LINC01500 (odds ratio = 0.72; 95% confidence interval: 0.58-0.88, log-additive model), and the rs11255841T>A SNP in the long noncoding RNA LINC00709 (odds ratio = 2.04; 95% confidence interval: 1.19-3.51, dominant model). Of interest, the observed associations were in the same direction than those reported for CRC risk. DISCUSSION: FDRs of CRC patients show significant differences in genotype distribution of SNPs related to CRC risk as compared to individuals with no family history of CRC. Genotyping of CRC risk variants in FDRs of CRC patients may help to identify subjects at risk that would benefit from stricter surveillance and CRC screening programs.

Automated summary

Epidemiological studies suggest that having a first-degree relative with colorectal cancer (CRC) increases the risk of developing the disease. This study found significant differences in genotype distribution of CRC risk-related SNPs between first-degree relatives of CRC patients and individuals with no family history of CRC. Genotyping of CRC risk variants in first-degree relatives of CRC patients could help identify individuals at risk who may benefit from increased surveillance and CRC screening programs.