Genetic variation in 8q24 associated with risk of colorectal cancer

Chromosome 8q24 harbors oncogenes known to be involved in pathogenesis of colorectal cancer (CRC) as well as uncharacterized genetic variants that have recently been shown to influence inherited risk of prostate cancer. In a population-based case-control study of colorectal cancer in northern Israel, we investigated the association between variation in 8q24 and risk of CRC. Among 1,861 incident cases and 1,937 population-based controls matched on age, gender, ethnicity, and clinic, rs10505477 was associated with risk of CRC in a dominant model, with an odds ratio = 1.23, 95% confidence interval = 1.05-1.43, (p = 0.008). This association was independently validated in an analysis of cancer among relatives of carriers of the risk allele, with a hazard ratio of 3.2 (95% bootstrap CI = 1.16-17.8). Genetic variation at rs10505477 on 8q24 potentially accounts for 14% of CRC in this population and should be replicated in other studies.