Lung cancer risk and genetic polymorphisms in DNA repair pathways: a meta-analysis

Abstract

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61-0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02-1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10-1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.

Figure 1

Meta-analysis of 8 studies (5 Caucasian studies and 3 non-Caucasian studies) of lung cancer and theXPA G23A polymorphism (GG versus AA). The center of a box and the horizontal line (logarithm) indicate the odds ratio (OR) and the 95% confidence interval (CI) in each study, with the areas of the boxes representing the weight of each study. The summary OR based on random effects model is represented by the middle of a diamond whose width indicated the 95% CI. The summary OR is shown by the dotted vertical line. Statistical heterogeneity between studies was assessed with Cochran Q test (Q = 7.86, P = .35). Summary: OR = 0.76 (95% CI = 0.61–0.94).

Figure 2

Meta-analysis of 10 Caucasian studies of lung cancer and the ERCC2 Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). The center of a box and the horizontal line (logarithm) indicate the odds ratio (OR) and the 95% confidence interval (CI) in each study, with the areas of the boxes representing the weight of each study. The summary OR based on random effects model is represented by the middle of a diamond whose width indicated the 95% CI. The summary OR is shown by the dotted vertical line. Statistical heterogeneity between studies was assessed with Cochran Q test(Q = 2.75, P = .97). Summary: OR = 1.24 (95% CI = 1.06–1.45).