Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, EPS 7060, MSC 7238, Bethesda, MD, 20892-7238, USA.
Breast Cancer Res Treat. 2009 Nov;118(1):177-84. doi: 10.1007/s10549-009-0307-3. Epub 2009 Feb 12.
Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1,083 controls within the US radiologic technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR = 0.3; 95% CI 0.1-0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR = 1.2; 95% CI 0.9-1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic X-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (p (interaction) = 0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic X-ray exposure (p (interaction) = 0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.
电离辐射相关乳腺癌风险似乎受生殖事件的时间影响，如辐射暴露时的年龄、产次、首次活产年龄和绝经年龄。然而，低至中度辐射剂量对多态雌激素代谢相关基因变异的潜在乳腺癌风险修饰尚未得到常规研究。我们在一项美国放射技师（USRT）队列中对 859 例病例和 1083 例对照进行了研究，评估了 12 个参与类固醇代谢、分解代谢、结合或受体功能的基因中 12 个候选变异的乳腺癌风险。使用详细评估职业和个人诊断电离辐射暴露的累积乳房剂量估计值，我们研究了基因型对乳腺癌风险的联合影响。在多变量分析中，我们观察到 CYP3A4 M445T 次要等位基因（rs4986910，OR=0.3；95%CI 0.1-0.9）与乳腺癌风险显著降低相关。我们发现 CYP1B1 V432L 的两个次要等位基因（rs1056836，CC 与 GG，OR=1.2；95%CI 0.9-1.6）与乳腺癌风险略有增加。假设隐性模型，CYP1B1 V432L 的次要等位基因显著增加了个人诊断 X 射线暴露与乳腺癌风险之间的剂量反应关系，调整了累积职业辐射剂量（p（交互）=0.03），并且在调整了个人诊断 X 射线暴露的累积职业辐射剂量时也具有类似的联合作用（p（交互）=0.06）。我们发现有证据表明，选定的雌激素代谢基因中的常见变异可能会修饰电离辐射暴露与乳腺癌风险之间的关联。
