Association Of Genetic Variants In ATR-CHEK1 And ATM-CHEK2 Pathway Genes With Risk Of Colorectal Cancer In A Chinese Population

OBJECTIVE: Colorectal cancer(CRC)is the third largest malignant tumor in the world.In the digestive system of malignant tumors,the morbidity and mortality rate ranked fourth.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:Ahospital-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 Taq Man 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.