Association of a novel genetic variant in RP11-650L12.2 with risk of colorectal cancer in Han Chinese population

Background: This study aimed to investigate the associations of selected polymorphisms in RP11-650L12.2 with the risk of colorectal cancer (CRC) in a Chinese population.

Methods: A total of 821 CRC cases (test set: 320, validation set: 501) and 857 healthy controls (test set: 319, validation set: 538) were enrolled in this study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. A sample of 5ml venous blood was collected from each subject for DNA isolation, and the selected polymorphisms (rs144182521, rs514743, rs76071148, rs149941240) were genotyped by MassArray technique.

Results: The rs149941240 polymorphism was significantly associated with the risk of CRC, with ORs of 1.50 (95% CI: 1.15-1.96) by co-dominant model and 1.45 (95% CI: 1.21-1.87) by dominant model in the test set, respectively. Correspondingly, the ORs were 1.48 (95% CI: 1.19-1.82) and 1.41 (95% CI: 1.15-1.73) in the validation set, respectively. The crossover analysis showed that non-smokers with the variant genotypes in rs149941240 had a significantly increased risk of CRC than those with wild genotype by dominant model in the validation set (OR 1.42, 95% CI 1.04-1.96). However, no gene-environment multiplicative interactions of rs149941240 with tobacco smoking were found on risk of CRC.

Conclusions: Our findings suggest that rs149941240 polymorphism was associated with the risk of CRC, and might contribute to the susceptibility to CRC. The effects of this polymorphism should be validated in a larger sample and require further mechanistic investigations to determine the nature of its influence on CRC.