Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

中文翻译：

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具有无法解释的 BRCA1 或 BRCA2 突变的乳腺癌遗传倾向的女性的诊断性胸部 X 光检查和乳腺癌风险


诊断电离辐射是乳腺癌 (BC) 的危险因素。乳腺癌风险随着胸部剂量的增加而增加，并随着暴露年龄的增加而降低，可能与家族或遗传易感性相关的效应改变。虽然与非携带者相比，胸部 X 光检查会增加 BRCA1/2 突变携带者的 BC 风险，但对于具有 BC 遗传倾向但 BRCA1 或 BRCA2 (BRCA1/2) 突变检测呈阴性的女性，我们知之甚少。我们在由法国家庭癌症诊所识别的 1552 例 BC 病例和 1363 例无关对照组成的数据集中评估了诊断医疗程序中胸部 X 光的效果。参与者在一份详细的调查问卷中报告了他们的 X 射线暴露史，并接受了 113 个 DNA 修复基因的测试。使用逻辑回归和多项逻辑回归模型来评估与 BC 的关联。胸部 X 光照射使 BC 风险增加一倍。每增加一次暴露，BC 风险就会增加 3%。首次接触年龄为 20 岁或以下，或者在第一次足月妊娠之前接触似乎不会改变这种风险。 1960 年以后出生或在 DNA 修复基因中携带除 BRCA1/2 以外的罕见的可能有害的编码变异会改变胸部 X 光照射的影响。无论首次接触时的年龄如何，曾经/从未接触过胸部 X 射线照射都会使 BC 风险增加 2 倍，而当 DNA 修复基因中携带 3 个或更多罕见变异时，乳腺癌风险会增加高达 5 倍。需要进一步的研究来评估其他 DNA 修复基因或变异体，以确定那些可以改变辐射敏感性的基因或变异体。鉴定对电离辐射或多或少敏感的亚群很重要，并且具有潜在的临床相关性。