EXO1 is a member of the RAD2 nuclease family and functions in DNA replication, repair and recombination. We investigated the relationship of single nucleotide polymorphisms (SNPs) at exon 10 (T439M) and exon 13 (P757L) of the EXO1 gene with development, progression and
metastasis of
colorectal cancer. For T439M, the Thr/Met genotype [odds ratio (OR) = 2.03, 95% confidence interval (CI) 1.04-3.98] and Thr/Met and
Met/Met genotypes combined (OR = 2.37, 95% CI 1.23-4.56) demonstrated significant association with the development of
colorectal cancer after adjusting for age, gender and smoking status. For P757L, patients with the
Leu/Leu genotype showed a reduced risk of
colorectal cancer (adjusted OR = 0.398, 95% CI 0.183-0.866) when the
Pro/Leu and
Pro/Pro genotypes were combined and used as the reference. The
Leu/Leu genotype also had a reduced risk (adjusted OR = 0.373, 95% CI 0.164-0.850) when the
Pro/Leu genotype was used as the reference. Individuals who carried both putative risk genotypes (Thr/Met and
Met/Met for T439M and
Pro/Leu for P757L) showed an adjusted OR of 4.95 (95% CI 1.56-15.7) compared with those who carried both low risk genotypes. Analysis of
microsatellite instability (MSI) revealed that
tumors from individuals who carried both putative risk genotypes tended to have a higher frequency of MSI positives than those from patients who carried both low risk genotypes, although a significant correlation was not found between EXO1 genotype and MSI status. This is the first report to provide evidence for an association of EXO1 gene polymorphisms with
colorectal cancer risk. The EXO1 genotypes were not associated with any clinicopathological characteristics in
colorectal cancer patients.