Background

Lung cancer among nonsmokers has been considered as a different disease from that among smokers. Involuntary smoking has been suggested to be a risk factor for lung cancer among nonsmokers with a modest effect. Few studies have examined the role of single nucleotide polymorphisms (SNPs) of the DNA repair genes and their potential interactions with involuntary smoking on the development of lung cancer among nonsmokers.

Methods

We evaluated the associations between SNPs of the DNA repair genes and lung cancer based on a pooled data of the International Lung Cancer Consortium. The individual-level epidemiological data and genotyping data on eight SNPs from six participating studies were pooled, including 845 nonsmoker cases and 4,262 nonsmoker controls. Logistic regression models with adjustment by age, sex, ethnicity, study, and ever involuntary smoking status were used to obtain odds ratios (OR) and 95% confidence intervals (CI).

Results

Among nonsmokers, the associations with the polymorphisms in OGG1 S326C and XPD D312N were observed among those with involuntary smoking (for OGG1 S326C: OR=1.61, 95% CI 1.18-2.20 for CG, OR=1.74, 0.99-3.06 for GG, compared to CC; for XPD D312N: OR=1.06, 0.76-1.47 for AG, OR=1.60, 1.06-2.42 for AA, compared to GG), but not for those without involuntary smoking (for OGG1 S326C: OR=0.78, 0.39-1.54 for CG, OR=0.88, 0.25-3.06 for GG, compared to CC; for XPD D312N: OR=1.13, 0.57-2.21 for AG, OR=0.81, 0.27-2.43 for AA, compared to GG). The association with XRCC3 T241M variant was detected for adenocarcinoma and non-small cell lung cancer among those without exposure to involuntary smoking (adenocarcinoma: OR=3.52, 1.21-10.20 for AA, OR=0.94, 0.38-2.38 for GA, compared to GG; and non-small cell lung cancer: OR=2.75, 1.05-7.21 for AA, OR=1.10, 0.51-2.38 for GA, compared to GG, respectively). Due to limited power, no apparent interaction between DNA repair SNPs and involuntary smoking was detected.

Conclusion

This is the first large-scale collaborative study on the relationship between DNA repair genetic variants and lung cancer among nonsmokers, accounting for involuntary smoking. Our results show that SNPs of the DNA repair genes may play an important role for lung cancer among nonsmokers, and the associations may vary by involuntary smoking status and histological subtype.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1869.