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The results show that\n                    <jats:bold>\n                      <jats:italic>\n                        GSTM1\n                        <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    confers an increased risk for breast cancer development compared with that in\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    \u2010present individuals (+\/+ and +\/\u2013), which was subsequently confirmed by a meta\u2010analysis of all of the 41 relevant studies (odds ratio: 1.10, P&lt;0.001). Unexpectedly, we found that\n                    <jats:bold>\n                      <jats:italic>\n                        GSTM1\n                        <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    is also a risk genotype compared with\n                    <jats:bold>\n                      <jats:italic>\n                        GSTM1\n                        <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      <\/jats:italic>\n                      .\n                    <\/jats:bold>\n                    Furthermore, we identified a functional polymorphism in the\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    promoter region associated with breast cancer. The variant allele modifies DNA binding to the AP\u20102\u03b1 transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low\u2010activity allele is associated with reduced breast cancer risk. It seems that ~60\u201370% expression from one allele of\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    could suffice for protection against breast cancer;null activity and overactivity of\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    are both disadvantageous. These results indicate a U\u2010shaped association of\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    with breast cancer, which challenges the linear gene\u2010dosage effect of\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    that was previously proposed. We recommend that a more complicated role for\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    should be considered in breast cancer risk prediction.\u2014Yu, K.D., Di, G.\u2010H., Fan, L., Wu, J., Hu, Z., Shen, Z.\u2010Z., Huang, W., Shao, Z.\u2010M. A functional polymorphism in the promoter region of\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    implies a complex role for\n                    <jats:bold>\n                      <jats:italic>GSTM1<\/jats:italic>\n                    <\/jats:bold>\n                    in breast cancer.\n                    <jats:italic>FASEBJ.<\/jats:italic>\n                    23, 2274\u20132287 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-124073","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T21:23:28Z","timestamp":1235078608000},"page":"2274-2287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["A functional polymorphism in the promoter region of\n                    <i>GSTM1<\/i>\n                    implies a complex role for\n                    <i>GSTM1<\/i>\n                    in breast cancer"],"prefix":"10.1096","volume":"23","author":[{"given":"Ke-Da","family":"Yu","sequence":"first","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen-Hong","family":"Di","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Fan","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Hu","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Zhou","family":"Shen","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese National Human Genome Center at Shanghai Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Ming","family":"Shao","sequence":"additional","affiliation":[{"name":"Breast Cancer Institute, Cancer Hospital Department of Oncology Shanghai Medical College, Institutes of Biomedical Science Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,19]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050776"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10937"},{"key":"e_1_2_15_4_1","first-page":"843","article-title":"A systematic review of genetic polymorphisms and breast cancer risk","volume":"8","author":"Dunning A.M.","year":"1999","journal-title":"Cancer Epidemiol. 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