《Nature》重磅！10万人研究！65个基因区域提高乳腺癌发病率！

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在乳腺癌的预防这一方面，我们得感谢一位好莱坞巨星：安吉丽娜朱莉。这位因为存在家族遗传而主动切除乳房的巨星，极大的推动了乳腺癌的科普工作。近年来，乳腺癌的防治和研究都有了巨大的进步。23日，发布在《Nature》上的一篇重磅文章，揭示了65个区域和女性乳腺癌发病率增高有关。

我们已知的易感基因中罕见的编码变体如BRCA1，以及许多常见的大多数非编码变异体，都会影响乳腺癌的风险。然而，很多基因在乳腺癌风险中的贡献却仍然未知。

而在此次《Nature》上面发表的文章，研究人员报告了共计122,977例乳腺癌全基因组关联研究结果，包括105974例欧洲血统对照组和14,068例对照组和13,104例东亚血统对照组。研究确定了65个同整体乳腺癌发病风险相关的新基因座。

这些基因座中的大部分可信危险单核苷酸多态性落在远端调控元件中，并通过计算机进行数据整合和预测靶基因在乳腺细胞中的作用，研究人员展示了候选靶基因和乳腺肿瘤体细胞驱动基因之间的强烈重叠效果。

与此同时，由于调节特征中的所有单核苷酸多态性，乳腺癌的遗传性相对于基因组平均值提高了2-5倍，对于特定的转录因子结合位点有更强的富集性。研究结果进一步确定了乳腺癌的遗传易感性，并会将数据用于改进遗传风险评分，以及在个体化筛查和预防中推广。

以下为研究结果相关数据：

SNP associations with breast cancer risk

Global mapping of biofeatures across novel loci associated with overall breast cancer risk

Pathway enrichment map for susceptibility

loci based on summary association statistics

Heat map showing patterns of cell-type-specific enrichments for breast tissue across three histone marks(H3K4me1, H3K4me3 and H3K9ac) for all breast cancer types,ER-positive breast cancer and ER-negative breast cancer as well as16 other traits

Heat map showing patterns of cell-type-specific enrichments for histone mark H3K27ac in all breast cancer types,ER-positive and ER-negative breast cancer as well as 16 other traits

Heat map showing patterns of cell-type-specific enrichments for histone mark H3K4me1 in all breast cancer types,ER-positive and ER-negative breast cancer as well as 16 other traits.

Heat map showing patterns of cell-type-specific enrichments for histone mark H3K4me3 in breast cancer overall,ER+ and ER- breast cancer as well as 16 other traits

Heat map showing patterns of cell-type-specific enrichments for histone marker H3K9ac in all breast cancer types,ER-positive and ER-negative breast cancer as well as 16 other traits

 Functional assessment of regulatory variants

at 1p36, 11p15 and 1p34 risk loci

Functional assessment of regulatory variants

at the 7q22 risk locus. a–e

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