XRCC1 and glutathione-S-transferase gene polymorphisms and susceptibility to radiotherapy-related malignancies in survivors of Hodgkin disease -: A report from the childhood cancer survivor study
XRCC1 and glutathione-S-transferase gene polymorphisms and susceptibility to radiotherapy-related malignancies in survivors of Hodgkin disease -: A report from the childhood cancer survivor study
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DOI：
10.1002/cncr.20520
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发表时间：
2004-09-15
期刊：
影响因子：
6.2
通讯作者：
Davies, SM
中科院分区：
文献类型：
--
作者：
Mertens, AC;Mitby, PA;Davies, SM
背景。儿童癌症治疗最严重的后期影响之一是随后发生恶性肿瘤。特别是霍奇金病（HD）的幸存者，其后续恶性肿瘤的风险很高，其发生与放射治疗暴露密切相关。在目前的研究中，作者调查了3个基因多态性-谷胱甘肽- s-转移酶M1 (GSTM1)，谷胱甘肽- s-转移酶T1 （GSTT1）和XRCC1之间的关系，这些基因在保护多种dna损伤剂中的作用-以及650名接受放疗的HD幸存者随后发生恶性肿瘤的风险。缺乏GSTM1而不缺乏GSTT1的个体在随后发生任何恶性肿瘤的风险增加（优势比[OR]， 1.5； 95%置信区间[CI]， 1.0-2.3），以及在辐射范围内发生后续癌症的风险增加（OR, 1.4; 95% CI, 0.9-2.1）。在缺乏GSTM1 （OR, 2.9; 95% CI, 0.8-10.9）或GSTT1 （OR, 3.7; 95% CI, 0.6-23.5）的个体中，甲状腺癌的风险没有显著增加。具有XRCC1基因密码子399处精氨酸/谷氨酰胺多态性基因型（11399）的个体与没有基因型的个体相比，患乳腺癌的风险没有显著增加（OR, 1.4; 95% CI, 0.7-2.7），随后患甲状腺癌的风险没有显著降低（OR, 0.6; 95% CI, 0.2-1.6）。与没有后续癌症的幸存者相比，基底细胞癌幸存者的基因型频率没有差异。这些数据说明了将基因组DNA收集纳入具有明确定义的潜在致癌暴露人群的纵向队列研究的潜在价值。对该队列中其他遗传多态性的评估可能有助于确定影响个体放射治疗敏感性的基因。(C) 2004年美国癌症协会。
BACKGROUND. One of the most serious late effects of treatment for childhood cancer is the occurrence of subsequent malignancy. Survivors of Hodgkin disease (HD), in particular, have been shown to be at high risk of subsequent malignancy, the occurrence of which has been associated strongly with exposure to radiotherapy.METHODS. In the current study, the authors investigated the association between polymorphisms in 3 genes-glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and XRCC1, with roles in protection from a variety of DNA-damaging agents-and the risk of subsequent malignancy in 650 survivors of HD enrolled in the Childhood Cancer Survivor Study who had received radiotherapy.RESULTS. individuals lacking GSTM1 but not GSTT1 were at increased risk of any subsequent malignancy (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.3), and for subsequent cancer within the radiation field (OR, 1.4; 95% CI, 0.9-2.1). A nonsignificant increased risk of thyroid carcinoma was observed in individuals lacking either GSTM1 (OR, 2.9; 95% CI, 0.8-10.9) or GSTT1 (OR, 3.7; 95% CI, 0.6-23.5). Individuals having the genotype of the arginine/glutamine polymorphism at codon 399 in the XRCC1 gene (11399) showed a nonsignificant increased risk of breast carcinoma compared with those without (OR, 1.4; 95% CI, 0.7-2.7), and a nonsignificant decreased risk against a subsequent thyroid carcinoma (OR, 0.6; 95% CI, 0.2-1.6). No differences in genotype frequencies were observed between survivors with basal cell carcinoma when compared with survivors without a subsequent cancer.CONCLUSIONS. These data illustrated the potential value of incorporating the collection of genomic DNA in longitudinal cohort studies of populations with well defined, potentially carcinogenic exposures. Evaluation of additional genetic polymorphisms in this cohort may help define genes that influence individual sensitivity to radiotherapy. (C) 2004 American Cancer Society.