Fasching P A, Ekici A B, Adamietz B R, Wachter D L, Hein A, Bayer C M, Häberle L, Loehberg C R, Jud S M, Heusinger K, Rübner M, Rauh C, Bani M R, Lux M P, Schulz-Wendtland R, Hartmann A, Beckmann M W
Universitäts-Brustzentrum Franken, Frauenklinik des Universitätsklinikums Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen-Nürnberg, Erlangen.
Institut für Humangenetik, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen.
Geburtshilfe Frauenheilkd. 2011 Dec;71(12):1056-1066. doi: 10.1055/s-0031-1280437.
The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case-control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patient's breast cancer risk.
在过去十年中，关于乳腺癌风险因素的可用信息急剧增加。特别是，对低外显率基因和乳腺X线密度的研究增进了我们对乳腺癌风险的理解。此外，在研究基因与环境因素之间的相互作用方面已经迈出了初步步伐。本综述关注该主题的实际数据。几项采用病例对照设计的全基因组关联研究（GWAS）以及大规模验证研究，已经识别并验证了十多种与乳腺癌风险相关的单核苷酸多态性（SNP）。它们不仅位于已知参与癌症发病机制的基因内部或附近，还位于先前与乳腺癌发病机制无关甚至可能与任何基因都无关的基因中。还发现了一些SNP，它们会改变突变携带者的终生风险。关于非遗传风险因素，绝经后激素替代疗法（HRT）的研究揭示了有关如何权衡HRT风险和益处的重要信息。乳腺X线密度（MD）已成为公认的重要乳腺癌风险因素。生活方式和营养因素已成为大多数乳腺癌风险研究不可或缺的一部分，并且在该领域也取得了一些进展。在首次使用他莫昔芬进行乳腺癌预防研究发表十多年后，已对雷洛昔芬和芳香化酶抑制剂等其他物质进行了研究，并且也显示出具有预防潜力。最后，在过去十年中，大多数西方国家都实施了乳腺X线筛查系统。通过纳入更多预测患者乳腺癌风险的个性化方法，这些系统可能会得到进一步发展。
