Kiyohara Chikako, Takayama Koichi, Nakanishi Yoichi
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Lung Cancer. 2006 Dec;54(3):267-83. doi: 10.1016/j.lungcan.2006.08.009. Epub 2006 Sep 18.
Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Although cigarette smoking is the main cause of lung cancer, not all smokers develop lung cancer, and a fraction of lifelong non-smokers will die from lung cancer. Genetic host factors have recently been implicated to account for some of the observed differences in lung cancer susceptibility. Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. Most of these alterations, if not repaired, may result in genetic instability, mutagenesis and cell death. DNA repair mechanisms are important for maintaining DNA integrity and preventing carcinogenesis. Recent genetic association studies on lung cancer risk have focused on identifying effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide base repair (BER) pathway, focusing on 8-oxoguanine DNA glycosylase 1, X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1. The 399Gln/Gln genotype of the XRCC1 Arg399Gln polymorphism was associated with an increased risk of lung cancer among Asians (OR=1.34, 95% CI=1.16-1.54) but not among Caucasians. Little evidence of associations has been found between other BER genes and lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between single SNP and lung cancer, this risk increase/decrease will probably be minimal. Advances in identification of new polymorphisms and in high-throughput genotyping techniques will facilitate 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.
肺癌是发达国家癌症相关死亡的主要原因，总体生存率仍然极低。尽管吸烟是肺癌的主要病因，但并非所有吸烟者都会患肺癌，而且一部分终生不吸烟者也会死于肺癌。最近有研究表明，遗传宿主因素可以解释肺癌易感性方面观察到的一些差异。接触环境和内源性致癌物可导致各种DNA改变。如果这些改变大多不被修复，可能会导致基因不稳定、诱变和细胞死亡。DNA修复机制对于维持DNA完整性和预防癌变很重要。最近关于肺癌风险的基因关联研究集中在确定候选基因中单核苷酸多态性（SNP）的影响，其中对DNA修复基因的研究越来越多。DNA修复基因的遗传变异被认为可调节DNA修复能力，并被认为与肺癌风险有关。我们确定了足够数量的关于肺癌的流行病学研究，以对核苷酸碱基修复（BER）途径中的基因多态性进行荟萃分析，重点关注8-氧代鸟嘌呤DNA糖基化酶1、X射线交叉互补组1（XRCC1）和脱嘌呤/脱嘧啶内切核酸酶1。XRCC1 Arg399Gln多态性的399Gln/Gln基因型与亚洲人患肺癌的风险增加有关（OR=1.34，95%CI=1.16-1.54），但在白种人中则不然。尚未发现其他BER基因与肺癌风险之间存在关联的证据。考虑到现有数据，可以推测，如果单个SNP与肺癌之间存在任何风险关联，这种风险的增加/降低可能很小。新多态性鉴定和高通量基因分型技术的进展将有助于分析多个DNA修复途径中的多个基因。因此，未来流行病学研究的一个显著特点可能是同时分析大量病例和对照样本。
