Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New Hampshire.
Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New Hampshire.
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DOI：
10.1289/ehp.10096
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发表时间：
2007-08
影响因子：
10.4
通讯作者：
Nelson HH
中科院分区：
文献类型：
--
作者：
Applebaum KM;Karagas MR;Hunter DJ;Catalano PJ;Byler SH;Morris S;Nelson HH
砷暴露可能会改变DNA修复的效率。紫外线损伤通过核苷酸切除修复（NER）进行特异性修复，NER中常见的遗传变异可能会增加非黑色素瘤皮肤癌（NMSC）的风险。我们测试了NER基因XPA（A23 G）和XPD（Asp 312 Asn和Lys 751 Gln）的多态性是否改变了砷和NMSC之间的关联。通过遍布新罕布什尔州的皮肤科医生和病理学实验室网络确定基底细胞癌和鳞状细胞癌（分别为BCC和SCC）的发病病例。以人群为基础的对照与病例的年龄和性别频率相匹配。砷暴露进行了评估，在脚趾甲剪。分析包括880例BCC，666例SCC和780例对照。在XPA纯合子变异体中，高砷暴露与BCC风险增加相关[比值比（OR）= 1.8; 95%置信区间（CI），0.9-3.7]。对于XPD，与对照组相比，BCC和SCC病例中两个位点（312 Asn和751 Gln）的变异发生率较低（OR = 0.8; 95%CI，0.6-1.0）。在两种XPD多态性都有变异的受试者中，砷含量升高与SCC的风险增加2倍（OR = 2.2; 95%CI，1.0-5.0）。XPD和砷在SCC中的相互作用的检验具有临界显著性（p < 0.07，3个自由度）。我们的研究结果表明，与XPD Asp 312 Asn和Lys 751 Gln变体相关的NMSC风险降低。此外，这些数据支持NER多态性可能改变NMSC和砷之间的关联的假设。
Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.
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影响因子：
10.4
作者：
Andrew AS;Burgess JL;Meza MM;Demidenko E;Waugh MG;Hamilton JW;Karagas MR
通讯作者：
Karagas MR
影响因子：
3.8
作者：
Han, JL;Colditz, GA;Hunter, DJ
通讯作者：
Hunter, DJ
影响因子：
4.7
作者：
Hou, SM;Fält, S;Hemminki, K
通讯作者：
Hemminki, K
DOI：
10.1177/096032718300200110
发表时间：
1983-01-01
期刊：
HUMAN TOXICOLOGY
影响因子：
--
作者：
CEBRIAN, ME;ALBORES, A;BLAKELY, E
通讯作者：
BLAKELY, E
影响因子：
8.8
作者：
Han, J;Hankinson, SE;Colditz, GA;Hunter, DJ
通讯作者：
Hunter, DJ