A genetic variant in the promoter of APE1 gene (-656 T>G) is associated with breast cancer risk and progression in a Chinese population

Abstract

Background/aims: APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (-656T>G and 1349T>G) and breast cancer risk.

Methods: We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results: We found that the variant genotypes of the -656T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.56-0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (<52 years) (OR=0.65, 95% CI=0.46-0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P=0.020, OR=0.64, 95% CI=0.44-0.94). We did not observe any significant association between the 1349T>G polymorphism and breast cancer risk.

Conclusion: Our results suggest that the APE1 -656T>G but not the 1349T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.

Keywords: AP endonuclease 1; APE1; BER; Breast cancer; CI; OR; Polymorphism; SNP; Susceptibility; base excision repair; confidence interval; odds ratio; single nucleotide polymorphism.