Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Cancers (Basel). 2010 Oct 28;2(4):1813-29. doi: 10.3390/cancers2041813.
Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg's and Egger's tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.
最近的肺癌研究集中在鉴定候选基因中单核苷酸多态性（SNPs）的作用上，其中 DNA 修复基因越来越受到关注。人们认为 DNA 修复基因的遗传变异可以调节 DNA 修复能力，并与肺癌风险有关。在这项研究中，我们试图评估已报道的人类 8-氧鸟嘌呤 DNA 糖基化酶 1（hOGG1）Ser326Cys 多态性与肺癌相关性的研究。我们使用“hOGG1”、“肺癌”和“多态性”作为关键词，在 MEDLINE、Current Contents 和 Web of Science 上进行了检索，以搜索 1995 年 1 月至 2010 年 8 月发表的论文。使用固定效应（倒数方差加权法）和随机效应（DerSimonian 和 Laird 法）模型合并数据。使用 Cochran Q 检验评估异质性。使用 Begg 和 Egger 检验评估发表偏倚。我们在 21 个不同的人群中确定了 20 项病例对照研究。由于有两项研究不符合 Hardy-Weinberg 平衡，因此我们将来自 19 个不同人群的 18 项病例对照研究（7792 例病例和 9358 例对照）纳入荟萃分析。基于随机效应模型，白种人和亚洲人 Cys 等位基因的汇总频率分别为 20.9%（95%置信区间[CI]为 18.9-22.9）和 46.1%（95%CI为 40.2-52.0）。Cys 等位基因在亚洲人和白种人中的分布有显著差异（P<0.001）。Cys/Cys 基因型与亚洲人群的肺癌风险显著相关（比值比=1.27，95%CI=1.09-1.48），但与白种人群无关。肺癌风险的这种种族差异可能是由于环境因素，如吸烟和饮食因素。虽然患肺癌的总体风险可能不大，但由于肺癌是一种常见的恶性肿瘤，即使风险略有增加，也会导致大量的肺癌病例增加。由于肺癌是一种多因素疾病，进一步研究 hOGG1 多态性与肺癌风险相关的基因-基因和基因-环境相互作用可能有助于更好地理解人类肺癌的分子发病机制。
