Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population.

Objective: The ATR-CHEK1 and ATM-CHEK2 pathway have been confirmed to be related with the DNA damage response (DDR). Many studies have reported that genetic variants in ATR/CHEK1 and ATM/CHEK2 are associated with cancer risk. However, the association between genetic variants in ATR-CHEK1, ATM-CHEK2 pathway genes and colorectal cancer susceptibility is still unknown. In this study, we aim to explore whether these variants are correlated with the risk of colorectal cancer in a Chinese population.

Methods: A hospital-based case-control study, including 1,121 cases and 1,056 controls was conducted to evaluate the association between eight selected single nucleotide polymorphisms (SNPs) (rs35514263 in ATR ; rs492510, rs558351 in CHKE1 ; rs189037 in ATM ; rs2236141, rs5762748, rs2236142 and rs9620817 in CHEK2 ) in ATR-CHEK1 and ATM-CHEK2 pathways and the risk of colorectal cancer in a Chinese population by using TaqMan method.

Results: Individuals with rs189037 A allele were found to have a significantly increased risk of colorectal cancer, compared to those carrying G allele [odds ratio(OR) = 1.23, 95% confidence interval (CI) = 1.02-1.47 in dominant model and OR= 1.14, 95%CI= 1.01-1.29 in additive model]. And this risk is more pronounced in elder people (>69), rectum, early stage and poorly grade. In addition, bioinformatic analysis showed that rs189037 may change the secondary structure.

Conclusions: Our results provide the evidence that rs189037 in ATM may increase the susceptibility of colorectal cancer in a Chinese population.