Yale School of Medicine, New Haven, Connecticut.
Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
Cancer Epidemiol Biomarkers Prev. 2018 Mar;27(3):285-294. doi: 10.1158/1055-9965.EPI-17-0319. Epub 2017 Dec 20.
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. 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. Three SNPs were associated with increased risk of thyroid cancer and with thyroid microcarcinoma: rs2708896, rs10951937, and rs12769288. No SNPs were associated with increased risk of larger tumor (>10 mm) in the additive model. The gene-environment interaction analysis yielded 24 SNPs with < 0.05 for all thyroid cancer, 12 SNPs with < 0.05 for thyroid microcarcinoma, and 5 SNPs with < 0.05 for larger tumors. 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. Thyroid microcarcinoma may represent a distinct subset of thyroid cancer. The effect of diagnostic radiation on thyroid cancer risk varies by germline polymorphism. .
辐射暴露是甲状腺癌的一个有据可查的风险因素；诊断性影像学代表了辐射暴露的一个不断增加的来源。DNA 修复基因的种系变异可能会增加诊断性辐射暴露后甲状腺癌的发病风险。目前尚无研究直接检测种系突变与辐射暴露之间的相互作用。利用 2010 年至 2011 年在康涅狄格州进行的一项基于人群的病例对照研究的数据和 DNA 样本，我们对 440 例新发病例甲状腺癌患者和 465 名基于人群的对照者进行了 52 个 DNA 修复基因中 296 个 SNP 的基因分型。我们使用多变量非条件逻辑回归模型来估计每个 SNP 与甲状腺癌风险之间的关联，以及直接估计每个 SNP 与电离辐射之间的基因型-环境相互作用。有三个 SNP 与甲状腺癌风险增加以及甲状腺微小癌有关：rs2708896、rs10951937 和 rs12769288。在加性模型中，没有 SNP 与更大肿瘤（>10mm）的风险增加相关。基因-环境相互作用分析产生了 24 个 SNP，所有甲状腺癌的 < 0.05，甲状腺微小癌的 12 个 SNP 的 < 0.05，较大肿瘤的 5 个 SNP 的 < 0.05。DNA 修复基因的种系变异与甲状腺癌风险相关，并与甲状腺微小癌和大肿瘤大小存在差异相关。本研究首次提供证据表明，种系遗传变异可修饰诊断性辐射与甲状腺癌风险之间的关联。甲状腺微小癌可能代表甲状腺癌的一个不同亚组。诊断性辐射对甲状腺癌风险的影响因种系多态性而异。
