Decades of research have shown that rare highly penetrant mutations can promote tumorigenesis, but it is still unclear whether variants observed at high-frequency in the broader population could modulate the risk of developing cancer. Genome-wide Association Studies (GWAS) have generated a wealth of data linking single nucleotide polymorphisms (SNPs) to increased cancer risk, but the effect of these mutations are usually subtle, leaving most of cancer heritability unexplained. Understanding the role of high-frequency mutations in cancer can provide new intervention points for early diagnostics, patient stratification and treatment in malignancies with high prevalence, such as breast cancer.

Here we review state-of-the-art methods to study cancer heritability using GWAS data and provide an updated map of breast cancer susceptibility loci at the SNP and gene level.

数十年的研究表明，罕见的高渗透突变可以促进肿瘤发生，但仍不清楚在更广泛的人群中高频观察到的变异是否可以调节患癌症的风险。全基因组关联研究 (GWAS) 已经产生了大量将单核苷酸多态性 (SNP) 与癌症风险增加联系起来的数据，但这些突变的影响通常很微妙，大部分癌症遗传性无法解释。了解高频突变在癌症中的作用可以为乳腺癌等高发病率恶性肿瘤的早期诊断、患者分层和治疗提供新的干预点。

在这里，我们回顾了使用 GWAS 数据研究癌症遗传力的最先进方法，并提供了 SNP 和基因水平的乳腺癌易感性位点的更新图。