Department of Medicine, Division of Epidemiology and Biostatistics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Invest Dermatol. 2012 May;132(5):1354-62. doi: 10.1038/jid.2012.4. Epub 2012 Feb 16.
Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
核苷酸切除修复 (NER) 负责保护皮肤细胞中的 DNA 免受 UVR 诱导的损伤。采用候选途径方法，对嵌套在前瞻性、基于社区的队列中的匹配病例对照研究进行了测试，以检验以下假设：NER 基因中的单核苷酸多态性 (SNP) 与非黑色素瘤皮肤癌 (NMSC) 的易感性有关。基于年龄、性别和皮肤类型，对组织学证实的 NMSC 病例 (n=900) 与对照 (n=900) 进行匹配。使用加性模型，ERCC6 中两个紧密连锁的功能 SNP 与 NMSC 风险增加显著相关：rs2228527(比值比 (OR) 1.57，95%置信区间 (CI) 1.20-2.05) 和 rs2228529(OR 1.57，95% CI 1.20-2.05)。这些关联仅限于皮肤基底细胞癌 (BCC) (rs2228529，OR 1.78，95% CI 1.30-2.44；rs2228527，OR 1.78，95% CI 1.31-2.43)。这些产生假说的发现表明，ERCC6 中的功能变体可能与 NMSC 风险增加有关，这种风险可能特定于 BCC。
