DNA repair, genetic variation and skin cancer

我们建议在护士健康研究中前瞻性评估候选DNA修复基因的低外显子多态性和单倍型与黑色素瘤和非黑素细胞皮肤癌（包括基底细胞癌（BCC）和鳞状细胞癌（SCC））风险的关系。我们假设三个重要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）的候选多态性和单倍型与皮肤癌的高风险相关。我们将进一步研究候选多态性是否改变阳光照射与皮肤癌风险之间的关系。从1989-90年到1998年，我们采集了743例皮肤癌病例（黑色素瘤177例，鳞状细胞癌283例，黑素瘤283例，黑素瘤283例，从确诊的黑素瘤病例中随机抽取）；每个病例将按年龄和种族与嵌套病例对照研究中的对照相匹配。

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.