Abstract
BackgroundNumerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.MethodsWe searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.ResultsThe results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98–1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13–1.48, and recessive model: OR = 1.19, 95% CI = 1.07–1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12–1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04–1.37, and recessive model OR = 1.23, 95% CI = 1.08–1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.ConclusionsDespite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.
Highlights
Cancer is recognized as the leading cause of death in economically developed countries and the second leading cause of death in developing countries
The distribution of genotypes for the OGG1 polymorphism in the controls of all studies was consistent with that expected from the Hardy-Weinberg equilibrium (HWE), except for three studies [23,35,36]
The study of Klinchid et al [20] was included only in the calculation of the dominant model, because the genotype distribution was not presented in sufficient detail
Summary
Cancer is recognized as the leading cause of death in economically developed countries and the second leading cause of death in developing countries. It has been estimated that approximately 12.7 million cancer cases and 7.6 million cancer deaths have been occurred in 2008. Lung cancer was the most commonly diagnosed type of cancer as well as the leading cause of cancer death in males in 2008. Lung cancer accounts for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths [1]. Cigarette smoking is the well known risk factor for lung cancer, which accounts for 80% of the worldwide lung cancer burden in males and at least 50% of the burden in females [2]. Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; the findings are inconsistent. We performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations
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