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  • Title: A systematic review of the relationship between polymorphic sites in the estrogen receptor-beta (ESR2) gene and breast cancer risk.
    Author: Yu KD, Rao NY, Chen AX, Fan L, Yang C, Shao ZM.
    Journal: Breast Cancer Res Treat; 2011 Feb; 126(1):37-45. PubMed ID: 20390341.
    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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