Polymorphisms in DNA double-strand break repair genes and skin cancer risk
Polymorphisms in DNA double-strand break repair genes and skin cancer risk
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DOI：
10.1158/0008-5472.can-04-0246
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发表时间：
2004-05-01
期刊：
影响因子：
11.2
通讯作者：
Hunter, DJ
中科院分区：
文献类型：
--
作者：
Han, JL;Colditz, GA;Hunter, DJ
紫外线可以引起大范围的DNA损伤。uva诱导的DNA氧化损伤和uvb诱导的光产物阻断DNA复制可导致双链断裂（DSBs）。我们选择了3个DSB修复基因XRCC2、XRCC3和LigaseIV中的11个单倍型标记单核苷酸多态性，并在护士健康研究中的巢式病例对照研究中评估了它们与皮肤癌风险的关系[219例黑色素瘤，286例鳞状细胞癌（SCC）， 300例基底细胞癌（BCC）和873例对照]。我们观察到，XRCC3 18085T （(241)Met）等位基因及其相关单倍型与SCC和BCC风险显著负相关，而XRCC3 4552C等位基因及其相关单倍型和XRCC2 30833A等位基因与BCC风险增加显著相关。LigaseIV 4044T和4062T等位基因与BCC风险降低相关；四种单倍型中的两种与改变的BCC风险显著相关。在那些携带大量低风险等位基因的人群中，发现了非黑色素瘤皮肤癌风险降低的趋势（趋势为P， SCC为0.05,BCC < 0.0001）。这些基因型对黑色素瘤风险的主要影响基本上是无效的。这项研究为DSB修复通路在皮肤癌发展中的作用提供了证据，特别是在BCC中。
UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 18085T ((241)Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly, associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, < 0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.