Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.
Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.
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DOI：
10.4137/bcbcr.s39384
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Danforth DN Jr
中科院分区：
文献类型：
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作者：
Danforth DN Jr
散发性乳腺癌是由于从青春期开始接触雌激素和其他致癌物而导致的正常乳腺组织中分子异常的积累，并持续到一生。这些分子变化可以采取多种形式，包括染色体数量和结构异常、表观遗传学变化和基因表达变化。为了确定这些异常的特征，对文献进行了回顾，以确定在被认为是散发性乳腺癌的正常风险或高风险的正常乳腺组织中，上述主要基因组类别中的每一个的分子变化。这篇综述指出，正常风险的乳腺组织(如缩乳术)包含早期乳腺癌发生的证据，包括杂合性丢失、抑癌基因和其他基因的DNA甲基化以及端粒缩短。在乳腺癌的高危正常组织中(如乳腺癌旁的正常乳腺组织或对侧乳腺)，这些变化持续存在，并伴随着非整倍体增加、基因组不稳定性增加、广泛的基因表达差异、大范围癌变区域的发展和增殖增加。这些变化与早期和长期接触致癌物质，特别是雌激素是一致的。提出了正常乳腺组织和高危乳腺组织的致癌途径模型。这些发现将澄清我们对正常乳腺组织中乳腺癌发生的理解，并促进改进的风险评估和妇女乳腺癌预防方法的发展。
Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women.