DNA repair, genetic variation and skin cancer

描述(由申请人提供)我们建议在护士健康研究中前瞻性地评估候选DNA修复基因的低外显度多态和单倍型与黑色素瘤和非黑色素细胞皮肤癌(包括基底细胞癌和鳞状细胞癌)风险的关系。我们假设三个重要的DNA修复基因(核苷酸切除修复中的XPD；碱基切除修复中的XRCC1；同源重组修复中的XRCC3)的候选多态和单倍型与皮肤癌的风险相关。我们将进一步研究候选基因的多态是否改变了阳光照射和皮肤癌风险之间的联系。自1989~1990年至1998年，我们共收集了743例皮肤癌的发病病例(从确诊的基底细胞癌病例中随机抽取177例黑色素瘤、283例鳞状细胞癌和283例基底细胞癌)，每个病例将按年龄和种族与嵌套病例对照研究中的对照病例相匹配。 我们将有90%的权力来检测大多数感兴趣的基因类型的主要影响的相对风险为1.5或更高。我们还将有相当大的能力来检测这些基因类型与终生阳光暴露之间的相互作用。 这项研究将是关于候选DNA修复基因的多态与皮肤癌之间关系的首批研究之一，该研究评估了基因和阳光暴露之间的潜在交互作用。

DESCRIPTION (provided by applicant)We propose to prospectively assess the association of low-penetrance polymorphisms and haplotypes in candidate DNA repair genes to the risk for melanoma and non-melanocytic skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the Nurses' Health Study. We hypothesize that candidate polymorphisms and haplotypes in three important DNA repair genes (XPD in nucleotide excision repair; XRCC1 in base excision repair; XRCC3 in homologous recombination repair) are associated with higher risk of skin cancer. We will further examine whether the candidate polymorphisms modify the association between the sunlight exposure and the risk of skin cancer. After blood collection in 1989-90 up to 1998, we have accrued 743 incident cases of skin cancers (177 melanoma, 283 SCC, and 283 BCC which were randomly selected from diagnosed BCC cases); each case will be matched by age and race to a control in the nested case-control study. We will have >90% power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and lifetime sunlight exposure. This study will be among the first studies of the association of polymorphisms in candidate DNA repair genes with skin cancer, which assess potential interactions between genotype and sunlight exposure.