Genetic variation in XPD, sun exposure, and risk of skin cancer
Genetic variation in XPD, sun exposure, and risk of skin cancer
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DOI：
10.1158/1055-9965.epi-04-0846
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发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Hunter, DJ
中科院分区：
文献类型：
--
作者：
Han, JL;Colditz, GA;Hunter, DJ
XPD基因参与核苷酸切除修复途径，去除紫外线辐射诱导的DNA光产物。XPD的遗传变异可能对DNA修复能力产生微妙的影响。我们评估了两种常见的非同义多态性（ASP（312）Asn和Lys（751）Gln）与皮肤癌风险之间的关系，在护士健康研究（219例黑色素瘤，286例鳞状细胞癌，300例基底细胞癌和874例对照）的巢式病例对照研究中，沿着对XPD基因单倍型结构的探索性分析。Lys（751）Gln和Asp（312）Asn多态性与黑色素瘤和鳞状细胞癌的风险呈负相关。这两种多态性与基底细胞癌风险之间没有相关性。我们还观察到，（751）Gln等位基因与黑色素瘤风险的相关性受到终身严重晒伤、泳衣累积日光暴露和体质易感性评分的影响（相互作用的P值分别为0.03、0.04和0.02）。在Asp（312）Asn中也观察到类似的相互作用。我们的数据表明，这两个XPD非同义多态性可能与皮肤癌的风险，特别是黑色素瘤。
The XPD gene is involved in the nucleotide excision repair pathway removing DNA photoproducts induced by UV radiation. Genetic variation in XPD may exert a subtle effect on DNA repair capacity. We assessed the associations between two common nonsynonymous polymorphisms (ASP(312)Asn and Lys(751)Gln) with skin cancer risk in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma, 300 basal cell carcinoma, and 874 controls) along with exploratory analysis on the haplotype structure of the XPD gene. There were inverse associations between the Lys(751)Gln and Asp(312)Asn polymorphisms and the risks of melanoma and squamous cell carcinoma. No association was observed between these two polymorphisms and basal cell carcinoma risk. We also observed that the association of the (751)Gln allele with melanoma risk was modified by lifetime severe sunburns, cumulative sun exposure with a bathing suit, and constitutional susceptibility score (P for interaction = 0.03, 0.04, and 0.02 respectively). Similar interactions were also observed for the Asp(312)Asn. Our data suggest these two XPD nonsynonymous polymorphisms may be associated with skin cancer risk, especially for melanoma.