文章：

筛查性乳腺X线摄影与乳腺癌：DNA修复基因罕见有害或预测有害变异对风险的影响差异

Screening Mammography and Breast Cancer: Variation in Risk with Rare Deleterious or Predicted Deleterious Variants in DNA Repair Genes

原文发布日期：21 March 2025

DOI: 10.3390/cancers17071062

类型: Article

开放获取: 是

英文摘要：

Background: Women with a familial predisposition to breast cancer (BC) are offered screening at earlier ages and more frequently than women from the general population. Methods: We evaluated the effect of screening mammography in 1552 BC cases with a hereditary predisposition to BC unexplained byBRCA1orBRCA2and 1363 unrelated controls. Participants reported their lifetime mammography exposures in a detailed questionnaire. Germline rare deleterious or predicted deleterious variants (D-PDVs) in 113 DNA repair genes were investigated in 82.5% of the women and classified according to the strength of their association with BC. Genes with an odds ratio (OR) < 0.9 was assigned to the Gene Group “Reduced”, those with OR ≥ 0.9 and ≤1.1 to Group “Independent”, and those with OR > 1.1 to Group “Increased”. Results: Overall, having been exposed to mammograms (never vs. ever) was not associated with BC risk. However, an increase in BC risk of 4% (95% CI: 1–6%) per additional exposure was found under the assumption of linearity. When grouped according to D-PDV carrier status, mammograms doubled the BC risk of women carrying a D-PDV in Group “Reduced”, as compared to those carrying a D-PDV in Group “Increased”. Conclusions: Our study is the first to investigate the joint effect of mammogram exposure and variants in DNA repair genes other thanBRCA1andBRCA2in women at high risk of BC; therefore, further studies are needed to verify our findings. Even though mammographic screening reduces the risk of mortality from BC, the identification of populations that are more or less susceptible to ionizing radiation may be clinically relevant.

摘要翻译： 

背景：与普通人群相比，具有乳腺癌家族遗传倾向的女性接受筛查的起始年龄更早、频率更高。方法：本研究评估了1552例具有非BRCA1/BRCA2基因解释的遗传性乳腺癌易感病例及1363例无关联对照人群的乳腺X线筛查效果。参与者通过详细问卷报告了其终生乳腺X线检查暴露史。对82.5%的女性进行了113个DNA修复基因的种系罕见有害或预测有害变异检测，并根据其与乳腺癌的关联强度进行分类：比值比<0.9的基因归入"风险降低"组，比值比≥0.9且≤1.1的归入"风险独立"组，比值比>1.1的归入"风险增加"组。结果：总体而言，是否接受过乳腺X线检查（从未检查vs.曾检查）与乳腺癌风险无显著关联。但在线性假设条件下，每增加一次检查暴露，乳腺癌风险增加4%（95% CI：1-6%）。按D-PDV携带状态分组分析发现，携带"风险降低"组D-PDV的女性，其乳腺X线检查导致的乳腺癌风险是携带"风险增加"组D-PDV女性的两倍。结论：本研究首次探讨了高危乳腺癌女性群体中乳腺X线暴露与非BRCA1/BRCA2的DNA修复基因变异的联合效应，因此需要进一步研究验证我们的发现。尽管乳腺X线筛查可降低乳腺癌死亡风险，但识别对电离辐射敏感性不同的群体具有临床意义。

原文链接：

Screening Mammography and Breast Cancer: Variation in Risk with Rare Deleterious or Predicted Deleterious Variants in DNA Repair Genes