We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794).
Our results provide evidence that the non-synonymous polymorphis</span>m of APEX1Asp(148)Glu may not be directly associated with lung cancer</span> risk, nor enhance the effects of smoking habit on lung cancer development.
However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp14</span>8Glu polymorphisms and lung cancer risk.
The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer.
In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.
The combined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association with risk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001).
Individuals carrying the APE1 Asp148Glu heterozygous and homozygous variant genotype had a 3.23-fold increased risk of lung cancer compared with these carrying the wild-type (Asp/Asp) genotype (p<0.0001), and those carrying the 148Glu homozygous genotype had a 3.17-fold increased risk (p=0.023).
In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk.
A common APE1 polymorphism, a T-->G transversion (Asp 148 Glu), was previously shown to be associated with risk of lung cancer, an association that was modified by cigarette smoking.
These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure.
Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA (-4G/A), XPD (Lys751Gln and Asp312Asn), XRCC1 (Arg399Gln), APE1 (Asp148Glu) and XRCC3 (Thr241Met).