Genetic variation in XRCC1, sun exposure, and risk of skin cancer.
Genetic variation in XRCC1, sun exposure, and risk of skin cancer.
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DOI：
10.1038/sj.bjc.6602174
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发表时间：
2004-10-18
影响因子：
8.8
通讯作者：
Hunter, DJ
中科院分区：
文献类型：
--
作者：
Han, J;Hankinson, SE;Colditz, GA;Hunter, DJ
XRCC1基因参与碱基切除修复途径。我们在护士健康研究的一项巢式病例对照研究中评估了XRCC1基因多态性和单倍型与皮肤癌风险的相关性（219例黑色素瘤，286例鳞状细胞癌（SCC）和300例基底细胞癌（BCC），以及873例对照）。我们对4个单倍型标记的单核苷酸多态性（Arg194Trp、C26602T、Arg399Gln和Gln632Gln）进行了基因分型。有没有显着差异，病例和对照组之间的频率分布的任何五个推断常见的单倍型。我们观察到399Gln等位基因与SCC风险呈负相关。这种负相关仅见于那些一生中有五次或五次以上晒伤的人，那些有皮肤癌家族史的人，以及那些在泳衣中累积阳光照射最高的三分位数的人，但不是那些由这些风险因素定义的低风险人群。我们还观察到194Trp等位基因携带与SCC风险增加显著相关，这是由皮肤癌家族史修改的。这两个多态性与BCC或黑色素瘤风险无关。我们的数据表明，Arg194Trp和Arg399Gln多态性可能与皮肤癌的风险不同，根据暴露剂量和皮肤癌的类型。
The XRCC1 gene is involved in the base excision repair pathway. We assessed the associations of polymorphisms and haplotypes in XRCC1 with skin cancer risk in a nested case–control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma (SCC) and 300 basal cell carcinoma (BCC), and 873 controls). We genotyped four haplotype-tagging single-nucleotide polymorphisms (Arg194Trp, C26602T, Arg399Gln, and Gln632Gln). There was no significant difference in frequency distribution between cases and controls for any of the five inferred common haplotypes. We observed that the 399Gln allele was inversely associated with SCC risk. This inverse association was only seen among those who had five or more lifetime sunburns, those with a family history of skin cancer, and those in the highest tertile of cumulative sun exposure in a bathing suit, but not among those with low risk defined by these risk factors. We also observed a significant association of the carriage of 194Trp allele with increased SCC risk, which was modified by family history of skin cancer. These two polymorphisms were not associated with BCC or melanoma risk. Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differently associated with skin cancer risk according to exposure dose and skin cancer type.
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影响因子：
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