Germline Variants in DNA Repair Genes, Diagnostic Radiation, and Risk of Thyroid Cancer.
Germline Variants in DNA Repair Genes, Diagnostic Radiation, and Risk of Thyroid Cancer.
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DNA 修复基因的种系变异、诊断放射和甲状腺癌的风险。
DOI：
10.1158/1055-9965.epi-17-0319
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Zhang,Yawei
中科院分区：
文献类型：
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作者：
Sandler,JasonE;Huang,Huang;Zhao,Nan;Wu,Weiwei;Liu,Fangfang;Ma,Shuangge;Udelsman,Robert;Zhang,Yawei
背景：辐射暴露是甲状腺癌的一个有据可查的危险因素;诊断成像是一个日益增加的暴露源。DNA修复基因的种系变异可能会增加诊断辐射照射后患甲状腺癌的风险。没有研究直接测试生殖系突变和radiation exposure.Methods之间的相互作用：使用数据和DNA样本从康涅狄格州人口为基础的病例对照研究在2010年至2011年进行，我们的基因型440例甲状腺癌和465个人口为基础的控制296 SNP在52个DNA修复基因。我们使用多变量非条件Logistic回归模型来估计每个SNP和甲状腺癌风险之间的关联，以及直接估计每个SNP和电离辐射之间的基因型-环境相互作用。结果：三个SNP与甲状腺癌和甲状腺微小癌的风险增加相关：HUSrs 2708896，HUSrs 10951937，andMGMTrs 12769288。在累加模型中，没有SNP与较大肿瘤（>10 mm）的风险增加相关。基因-环境交互作用分析得到24个SNPs的Pinteraction < 0.05的所有甲状腺癌，12个SNPs的Pinteraction < 0.05的甲状腺微小癌，和5个SNPs的Pinteraction < 0.05的较大tumors.Conclusions：DNA修复基因的生殖系变异与甲状腺癌的风险，并与甲状腺微小癌和大肿瘤大小的差异。我们的研究提供了第一个证据，生殖系遗传变异修改诊断辐射和甲状腺癌risk.Impact之间的关联：甲状腺微小癌可能代表甲状腺癌的一个独特的子集。诊断辐射对甲状腺癌风险的影响因生殖系多态性而异。癌症流行病学生物标志物Prev; 27（3）; 285-94。©2017 AACR.
Background:Radiation exposure is a well-documented risk factor for thyroid cancer; diagnostic imaging represents an increasing source of exposure. Germline variations in DNA repair genes could increase risk of developing thyroid cancer following diagnostic radiation exposure. No studies have directly tested for interaction between germline mutations and radiation exposure.Methods:Using data and DNA samples from a Connecticut population–based case–control study performed in 2010 to 2011, we genotyped 440 cases of incident thyroid cancer and 465 population-based controls for 296 SNPs in 52 DNA repair genes. We used multivariate unconditional logistic regression models to estimate associations between each SNP and thyroid cancer risk, as well as to directly estimate the genotype–environment interaction between each SNP and ionizing radiation.Results:Three SNPs were associated with increased risk of thyroid cancer and with thyroid microcarcinoma:HUSrs2708896,HUSrs10951937, andMGMTrs12769288. No SNPs were associated with increased risk of larger tumor (>10 mm) in the additive model. The gene–environment interaction analysis yielded 24 SNPs withPinteraction< 0.05 for all thyroid cancer, 12 SNPs withPinteraction< 0.05 for thyroid microcarcinoma, and 5 SNPs withPinteraction< 0.05 for larger tumors.Conclusions:Germline variants in DNA repair genes are associated with thyroid cancer risk and are differentially associated with thyroid microcarcinoma and large tumor size. Our study provides the first evidence that germline genetic variations modify the association between diagnostic radiation and thyroid cancer risk.Impact:Thyroid microcarcinoma may represent a distinct subset of thyroid cancer. The effect of diagnostic radiation on thyroid cancer risk varies by germline polymorphism.Cancer Epidemiol Biomarkers Prev; 27(3); 285–94. ©2017 AACR.