A polymorphism in the APE1 gene promoter is associated with lung cancer risk.
Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway, which is the primary mechanism for the repair of DNA damage caused by oxidation and alkylation. We hypothesized that polymorphisms of APE1 are associated with risk for lung cancer. In the hospital-based matched case-control study, a total of 730 lung cancer cases and 730 cancer-free controls were genotyped for four APE1 haplotype-tagging polymorphisms (that is, -656T>G, 400A>G, 630T>C, and 1350T>G). Among them, the single-nucleotide polymorphism -656T>G located in the promoter region of APE1 was significantly associated with risk for lung cancer. We found that, compared with -656 TT homozygotes, the variant genotypes were associated with a significantly decreased risk [adjusted odds ratio, 0.51; 95% confidence interval (95% CI), 0.33-0.79 for -656 TG; adjusted odds ratio, 0.43; 95% CI, 0.25-0.76 for -656 GG, respectively]. Furthermore, we found a statistically significant reduced risk of -656T>G variants among heavy smokers (adjusted odds ratio, 0.52; 95% CI, 0.30-0.93 for -656 TG; adjusted odds ratio, 0.27; 95% CI, 0.13-0.57 for -656 GG, respectively), with a significant gene-smoking interaction (P = 0.013). A similar gene-smoking interaction in the context of APE1 haplotypes was also observed. The in vitro promoter assay revealed that the -656 G allele had a significantly higher transcriptional activity than that of the -656 T allele. Together, our results suggest that polymorphisms of the APE1 gene possibly interact with smoking and may contribute to the development of lung cancer.
Lo
Yen-Li
YL
Division of Biostatistics and Bioinformatics, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.
Jou
Yuh-Shan
YS
Hsiao
Chin-Fu
CF
Chang
Gee-Chen
GC
Tsai
Ying-Huang
YH
Su
Wu-Chou
WC
Chen
Kuan-Yu
KY
Chen
Yuh-Min
YM
Huang
Ming-Shyan
MS
Hu
Chi Yuan
CY
Chen
Chien-Jen
CJ
Hsiung
Chao A
CA
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D013624:Taiwan / Q000453:epidemiology
C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase