Benhamou Simone, Sarasin Alain
Institut National de la Santé et de la Recherche Médicale-Evry University, 91034 Evry, France.
Am J Epidemiol. 2005 Jan 1;161(1):1-14. doi: 10.1093/aje/kwi018.
The xeroderma pigmentosum group D (XPD) protein is a well-characterized DNA helicase necessary for the nucleotide excision repair of bulky DNA lesions, such as those induced by cigarette smoking. Polymorphisms in several exons of the XPD gene have been identified; two of them, Asp312Asn and Lys751Gln, are common and result in an amino acid change. Most of the reported data indicate higher levels of DNA adducts in people carrying variant Asn or Gln alleles, which suggests that these persons have lower repair efficiency. These two polymorphisms have been hypothesized to modify the risk of lung cancer. To examine this association, the authors undertook a review and meta-analyses of nine published case-control studies. No clear association between XPD Asp312Asn or XPD Lys751Gln gene polymorphisms and lung cancer was found. However, it may be only the joint effect of multiple polymorphisms within the gene that provides information about an association with lung cancer. Because of advances in high-throughput genotyping techniques, it is likely that future association studies on lung cancer will need to investigate multiple polymorphisms within genes and multiple genes within the same pathway and will need to use recently developed haplotype-based methods to evaluate the haplotypic effects.
着色性干皮病D组（XPD）蛋白是一种已被充分表征的DNA解旋酶，对于诸如吸烟诱导的那些大片段DNA损伤的核苷酸切除修复是必需的。XPD基因几个外显子中的多态性已被识别；其中两个，Asp312Asn和Lys751Gln，较为常见且导致氨基酸改变。大多数已报道的数据表明，携带Asn或Gln变异等位基因的人DNA加合物水平较高，这表明这些人修复效率较低。这两种多态性被推测会改变肺癌风险。为检验这种关联，作者对九项已发表的病例对照研究进行了综述和荟萃分析。未发现XPD Asp312Asn或XPD Lys751Gln基因多态性与肺癌之间存在明确关联。然而，可能只有基因内多个多态性的联合效应才提供与肺癌关联的信息。由于高通量基因分型技术的进展，未来关于肺癌的关联研究可能需要调查基因内的多个多态性以及同一途径内的多个基因，并且需要使用最近开发的基于单倍型的方法来评估单倍型效应。
