Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma
Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma
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DOI：
10.1677/erc-08-0336
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Yamashita, Shunichi
中科院分区：
文献类型：
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作者：
Akulevich, Natallia M.;Saenko, Vladimir A.;Yamashita, Shunichi
甲状腺乳头状癌（PTC）是一种放射性或散发性的恶性肿瘤，其遗传因素尚不清楚。在这项回顾性病例对照研究中，我们评估了候选DNA损伤反应基因（ATM，XRCC 1，TP 53，XRCC 3，MTF 1）中的单核苷酸多态性（SNIPS）与辐射诱导和散发性PTC风险之间的可能关联。共有255例PTC病例（123例切尔诺贝利辐射诱导和132例散发，均为高加索人）和596例健康对照（198例切尔诺贝利地区居民和398例无辐射暴露史的受试者，均为高加索人）进行了基因分型。PTC和SNPs与辐射暴露的相互作用的风险通过逻辑回归进行评估。根据遗传的乘法和显性模型，ATM G5557 A和XRCC 1 Arg 399 Gln多态性与PTC风险降低相关（比值比（OR）分别为0.69，95%置信区间（CI）0.45-0.86和OR = 0.70，95% CI 0.59-0.93）。ATMIVS 22 -77 T > C和TP 53 Arg 72 Pro单核苷酸多态性与辐射有交互作用（分别为P = 0.04和P = 0.01）。ATMIVS 22 -77与散发性PTC的发病风险增加相关（OR = 1.84，95% CI 1.10-3.24），TP 53 Arg 72 Pro与放射源性PTC的发病风险增加相关（OR = 1.80，95% CI 1.06-2.36）。在ATM/TP 53（rs 1801516/rs664677/rs609429/rs 1042522）组合分析中，GG/TC/CG/GC基因型与辐射诱导的PTC密切相关（OR = 2.10，95%CI 1.17-3.78）。GG/CC/GG/GG基因型与散发性PTC的发病风险显著相关（OR = 3.32，95% CI 1.57 ~ 6.99）。结果表明，DNA损伤反应基因的多态性可能是电离辐射诱发或散发性PTC的潜在风险调节因子。
Papillary thyroid carcinoma (PTC) etiologically occurs as a radiation-induced or sporadic malignancy Genetic factors contributing to the susceptibility to either form remain unknown. In this retrospective case-control study, we evaluated possible associations between single-nucleotide polymorphisms (SNIPS) in the candidate DNA damage response genes (ATM, XRCC1, TP53, XRCC3, MTF1) and risk of radiation-induced and sporadic PTC. A total of 255 PTC cases (123 Chernobyl radiation-induced and 132 sporadic, all in Caucasians) and 596 healthy controls (198 residents of Chernobyl areas and 398 subjects without history of radiation exposure, all Caucasians) were genotyped. The risk of PTC and SNPs interactions with radiation exposure were assessed by logistic regressions. The ATM G5557A and XRCC1 Arg399Gln polymorphisms, regardless of radiation exposure, associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.45-0.86 and OR = 0.70, 95% Cl 0.59-0.93 respectively). The ATM IVS22-77 T > C and TP53 Arg72Pro SNPs interacted with radiation (P = 0.04 and P = 0 01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (OR = 1.84, 95% Cl 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (OR = 1 80, 95% Cl 1.06-2.36). In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (OR = 2.10, 95% Cl 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (OR = 3 32, 95% Cl 1 57-6.99). The results indicate that polymorphisms of DNA damage response genes may be potential risk modifiers of ionizing radiation-induced or sporadic PTCs.