Woodward Emma R, van Veen Elke M, Evans D Gareth
Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Breast Care (Basel). 2021 Jun;16(3):202-213. doi: 10.1159/000515319. Epub 2021 Mar 31.
There has been huge progress over the last 30 years in identifying the familial component of breast cancer.
Currently around 20% is explained by the high-risk genes and , a further 2% by other high-penetrance genes, and around 5% by the moderate risk genes and . In contrast, the more than 300 low-penetrance single-nucleotide polymorphisms (SNP) now account for around 28% and they are predicted to account for most of the remaining 45% yet to be found. Even for high-risk genes which confer a 40-90% risk of breast cancer, these SNP can substantially affect the level of breast cancer risk. Indeed, the strength of family history and hormonal and reproductive factors is very important in assessing risk even for a BRCA carrier. The risks of contralateral breast cancer are also affected by SNP as well as by the presence of high or moderate risk genes. Genetic testing using gene panels is now commonplace.
KEY-MESSAGES: There is a need for a more parsimonious approach to panels only testing those genes with a definite 2-fold increased risk and only testing those genes with challenging management implications, such as and , when there is strong clinical indication to do so. Testing of SNP alongside genes is likely to provide a more accurate risk assessment.
在过去30年里，在确定乳腺癌的家族性因素方面取得了巨大进展。
目前，约20%可由高危基因 和 解释，另外2%由其他高 penetrance 基因解释，约5%由中度风险基因 和 解释。相比之下，现在300多个低 penetrance 单核苷酸多态性（SNP）约占28%，预计它们将占尚未发现的其余45%的大部分。即使对于赋予40 - 90%乳腺癌风险的高危基因，这些SNP也会显著影响乳腺癌风险水平。实际上，家族史以及激素和生殖因素的强度在评估风险时非常重要，即使对于BRCA携带者也是如此。对侧乳腺癌的风险也受SNP以及高危或中度风险基因的存在影响。使用基因panel进行基因检测现在很常见。
需要采用更简约的方法来进行panel检测，仅检测那些风险明确增加两倍的基因，并且仅在有强烈临床指征时检测那些具有挑战性管理意义的基因，如 和 。同时检测SNP和基因可能会提供更准确的风险评估。
