Hilakivi-Clarke Leena, de Assis Sonia
Georgetown University, Washington DC 20057, USA.
Trends Endocrinol Metab. 2006 Nov;17(9):340-8. doi: 10.1016/j.tem.2006.09.002. Epub 2006 Sep 25.
Susceptibility to breast cancer might be pre-determined in utero. Alterations in the fetal hormonal environment, caused by either maternal diet or exposure to environmental factors with endocrine activities, can modify the epigenome, and these modifications are inherited in somatic daughter cells and maintained throughout life. These epigenetic modifications might lead to changes in mammary gland development, such as increased vulnerability of epithelial targets for malignant transformation. According to this hypothesis, on post-pubertal exposure to an initiating factor, such as a carcinogen, high levels of hormones and radiation, the mammary epithelial targets, perhaps stem cells, in terminal end buds/terminal ductal lobular units would be at an increased risk of malignant transformation. The increased susceptibility for cancer initiation might result from high levels of cell proliferation, reduced apoptosis and/or altered stromal regulation. Thus, maternal diet and environmental exposure might increase the risk of breast cancer by inducing permanent epigenetic changes in the fetus that alter the susceptibility to factors that can initiate breast cancer. Identifying the epigenetically altered target genes and their ligands might lead to strategies to prevent this disease in some women.
乳腺癌易感性可能在子宫内就已预先确定。由母亲饮食或接触具有内分泌活性的环境因素所导致的胎儿激素环境改变，能够修饰表观基因组，并且这些修饰会在体细胞子代细胞中遗传并终生维持。这些表观遗传修饰可能会导致乳腺发育的变化，例如上皮细胞靶点发生恶性转化的易感性增加。根据这一假说，在青春期后接触启动因子，如致癌物、高水平激素和辐射时，终末芽/终末导管小叶单位中的乳腺上皮靶点，可能是干细胞，发生恶性转化的风险会增加。癌症起始易感性增加可能是由于细胞增殖水平高、细胞凋亡减少和/或基质调节改变所致。因此，母亲的饮食和环境暴露可能会通过在胎儿中诱导永久性的表观遗传变化，改变对引发乳腺癌因素的易感性，从而增加患乳腺癌的风险。识别表观遗传改变的靶基因及其配体，可能会为某些女性预防这种疾病带来策略。
