A systematic review of the relationship between polymorphic sites in the <Emphasis Type="Italic">estrogen receptor</Emphasis>-<Emphasis Type="Italic">beta</Emphasis> (<Emphasis Type="Italic">ESR2</Emphasis>) gene and breast cancer risk |
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Authors: | Ke-Da Yu Nan-Yan Rao Ao-Xiang Chen Lei Fan Chen Yang Zhi-Ming Shao |
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Institution: | (1) Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, 200032 Shanghai, People’s Republic of China;(2) Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China;(3) Department of Breast Surgery, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China;(4) Institutes of Biomedical Science, Fudan University, Shanghai, People’s Republic of China; |
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Abstract: | The estrogen signal is mediated by the estrogen receptor (ER). The specific role of ER-beta, a second ER, in breast carcinogenesis
is not known. A number of association studies have been carried out to investigate the relationship between polymorphic sites
in the ESR2 gene and breast cancer risk, however, the results are inconsistent. We searched PubMed, Medline, and Web of Science database
(updated to 10 January 2010) and identified 13 relevant case–control studies, and approximately 28 single-nucleotide polymorphisms
(SNPs) and one micro-satellite marker were reported in the literature. The median number of study subjects was 776 (range
158–13,550). Three genetic variants (CA)n, rs2987983, and rs4986938] showed significant overall associations with breast cancer, and rs4986938 was reported twice.
Because rs4986938 and rs1256049 were the most extensively studied polymorphisms, we subsequently conducted a meta-analysis
to evaluate their relationship with breast cancer risk (9 studies of 10,837 cases and 16,021 controls for rs4986938; 8 studies
of 11,652 cases and 15,726 controls for rs1256049). For rs4986938, the women harboring variant allele seemed to be associated
with a decreased risk either in the dominant model pooled OR = 0.944, 95% confidence interval (95% CI) 0.897–0.993, fixed-effects]
or in the co-dominant model (AG vs. GG) (OR = 0.944, 95% CI 0.895–0.997, fixed-effects). rs1256049 was not associated with
breast cancer risk in any model. Five studies had investigated the effect of haplotypes in the ESR2 gene on breast cancer risk, and four of them had positive outcomes. In summary, the present systematic review suggests that
SNP rs4986938 as well as haplotypes in the ESR2 gene might be associated with breast cancer. The need for additional studies examining these issues seems of vital importance. |
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