- 作者: Jyh-Cherng Yu; Huan-Ming Hsu; Shou-Tung Chen; Giu-Cheng Hsu; Chiun-Sheng Huang; Ming-Feng Hou; Yi-Ping Fu; Ting-Chih Cheng; Pei-Ei Wu; Chen-Yang Shen
- 作者服務機構: 1 Departments of Surgery, Tri-Service General Hospital, Taipei, Taiwan; ; 2 Institute of Biomedical Sciences, Academia S璯ica, Taipei, Taiwan;; 3 Division of General Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; ; 4 Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan; ; 5 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; ; 6 Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;; 7 Life Science Library, Academia S璯ica, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumor promotion. In addition to its role in regulating target genes and signaling pathways involved in cell cycle progression, the ER-signaling pathway may regulate the expression of chromatin-remodeling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodeling protein, Metastasis-associated 1 (MTA1). The invasion-suppressor gene, E-Cadherin (Ε-Cad), has recently been identified as a downstream target gene regulated by the ER-MTA3 pathway via the transcriptional repressor, Snail, and the ER-MTA3-Snail-E-Cad pathway has therefore been evoked to explain the clinical observation that ER expression in breast cancer is generally associated with a better clinical outcome. Since E-Cad may play an initiating role during breast tumorigenesis, we hypothesized that this ER-signaling pathway may also determine susceptibility to breast cancer, and examined this in a multigenic case-control study of 468 incident breast cancer patients and 470 healthy controls by genotyping the single nucleotide polymorphisms (SNPs) in five genes (ER, MTA3, Snail, E-Cad, and MTA1) in the ER-signaling pathways. Support for this hypothesis came from the observations that (a) with the exception of Snail, which interacted differently with reproductive risk factors in relation to breast cancer risk, there was a joint effect of the SNPs of these genes and estrogen-related risk factors (age at first full-term pregnancy and obesity, measured by the body mass index) on breast cancer risk (p < 0.05); (b) a trend toward increased risk of developing breast cancer was seen in women harboring a greater number of putative high-risk genotypes of these genes in ER-signaling pathways; (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to have experienced higher estrogen level, i.e., obese women; and (d) the risk effect conferred by obesity was only significant in women with a higher number of putative high-risk genotypes of the ER-signaling genes. These epidemiological findings highlight the role of newly identified novel ER-related
- 中文關鍵字: --
- 英文關鍵字: breast cancer, E-cadherin, estrogen, estrogen receptor, genetic polymorphism, MTAl, MTA3, snail