Single Nucleotide Polymorphism In The HEXO1 Gene Associates With Colorectal Cancer Risk In A Chinese Population

Changes in the efficiency of DNA repair and recombination activities can lead to an elevated susceptibility to cancer, Human exonuclease 1(hEXO1) has been implicated play an important role in DNA replication, recombination and repair, Recently many studies have focused on the relationship between the genetic polymorphisms and the risk of colorectal cancer, however, few studies have previously examined the relation between the single nucleotide polymorphisms (SNPs) of hEXO1 gene and the risk of colorectal cancer (CRC). This study investigated the relation of single nucleotide polymorphisms, 49C→T polymorphism in exon 10 and 59C→T polymorphism in exon 13 of the hEXO1 gene to colorectal cancer in a hospital-based case-control study in Shanxi province of China. The subjects comprised 230 incident cases of histologically confirmed colorectal cancer and 168 controls selected randomly in the same area. The genotype was determined by the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method using genomic DNA extracted from peripheral blood. The frequency of the hEXO1 exon10 T allele was 17.2% in the cases and 10.4% in the controls, and the genotype frequency of hEXO1 C/C, C/T, and T/T were 68.7%, 28.3%, and 3.0%, respectively, in the cases, and 80.9%, 17.3%, and 1.8%, respectively, in the controls. There was significant difference in the genotype frequencies of the SNP between normal control and CRC patients(χ~2 test, p=0.023). The genotype frequency of hEXO1 exon13 C/C, C/T, and T/T were 17.0%, 43.5%, and 39.5%, respectively, in the cases, and 8.3%, 51.2%, and 40.5, respectively, in the controls. There was significant difference in the genotype frequencies of the SNP between normal control and CRC patients(χ~2 test, p=0.035). For exon10 C49T, the 49C/T genotype (OR=1.929, 95%CI, 1.177-3.162), the 49T/T genotype (OR=2.008, 95%CI, 0.509-7.918) and 49C/T and 49T/T genotypes combined (OR=1.937, 95%CI, 1.024-3.115) demonstrated significant association with the risk of CRC compared with 49C/C common genotype. The odds ratio of T allele to C allele was 1.783(95%CI, 1.165-2.729). For exon13 C59T, the 59C/C genotype (OR=2.082, 95%CI, 1.048-4.137) demonstrated significant association with the risk of CRC compared with 59T/T genotype. The odds ratio of C allele to T allele was 1.229(95%CI, 0.916-1.649).