A systematic review of the relationship between polymorphic sites in the estrogen receptor-beta (ESR2) gene and breast cancer risk
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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.
KeywordsESR2 Polymorphism Breast cancer Systematic review Meta-analysis
This research is supported by grants from the National Basic Research Program of China (2006CB910501), 2009 Youth Foundation of Shanghai Public Health Bureau, 2009 Youth Foundation of Shanghai Medical College, and the National Natural Science Foundation of China (30971143, 30972936).
Conflict of interest statement
All authors declared no potential conflicts of interest.
- 11.Chen YC, Kraft P, Bretsky P, Ketkar S, Hunter DJ, Albanes D, Altshuler D, Andriole G, Berg CD, Boeing H, Burtt N, Bueno-de-Mesquita B, Cann H, Canzian F, Chanock S, Dunning A, Feigelson HS, Freedman M, Gaziano JM, Giovannucci E, Sanchez MJ, Haiman CA, Hallmans G, Hayes RB, Henderson BE, Hirschhorn J, Kaaks R, Key TJ, Kolonel LN, LeMarchand L, Ma J, Overvad K, Palli D, Pharaoh P, Pike M, Riboli E, Rodriguez C, Setiawan VW, Stampfer M, Stram DO, Thomas G, Thun MJ, Travis RC, Virtamo J, Trichopoulou A, Wacholder S, Weinstein SJ (2007) Sequence variants of estrogen receptor beta and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. Cancer Epidemiol Biomarkers Prev 16:1973–1981CrossRefPubMedGoogle Scholar
- 14.Yu KD, Chen AX, Yang C, Qiu LX, Fan L, Xu WH, Shao ZM (2009) Current evidence on the relationship between polymorphisms in the COX-2 gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat (in press). doi: 10.1007/s10549-009-0688-3
- 18.Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K, Ellis N, Huang H, Chen M, Lippert R, Halldorsson BV, Woodworth B, White T, Clark AG, Parl FF, Broder S, Dean M, Offit K (2004) Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res 64:8891–8900CrossRefPubMedGoogle Scholar
- 20.Gallicchio L, Berndt SI, McSorley MA, Newschaffer CJ, Thuita LW, Argani P, Hoffman SC, Helzlsouer KJ (2006) Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease. BMC Cancer 6:173CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Tsezou A, Tzetis M, Gennatas C, Giannatou E, Pampanos A, Malamis G, Kanavakis E, Kitsiou S (2008) Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer. Breast 17:159–166CrossRefPubMedGoogle Scholar
- 23.Cox DG, Bretsky P, Kraft P, Pharoah P, Albanes D, Altshuler D, Amiano P, Berglund G, Boeing H, Buring J, Burtt N, Calle EE, Canzian F, Chanock S, Clavel-Chapelon F, Colditz GA, Feigelson HS, Haiman CA, Hankinson SE, Hirschhorn J, Henderson BE, Hoover R, Hunter DJ, Kaaks R, Kolonel L, LeMarchand L, Lund E, Palli D, Peeters PH, Pike MC, Riboli E, Stram DO, Thun M, Tjonneland A, Travis RC, Trichopoulos D, Yeager M (2008) Haplotypes of the estrogen receptor beta gene and breast cancer risk. Int J Cancer 122:387–392CrossRefPubMedGoogle Scholar
- 25.Sonestedt E, Ivarsson MI, Harlid S, Ericson U, Gullberg B, Carlson J, Olsson H, Adlercreutz H, Wirfalt E (2009) The protective association of high plasma enterolactone with breast cancer is reasonably robust in women with polymorphisms in the estrogen receptor alpha and beta genes. J Nutr 139:993–1001CrossRefPubMedGoogle Scholar
- 27.Abbas S, Brauch H, Chang-Claude J, Dunnebier T, Flesch-Janys D, Hamann U, Hein R, Justenhoven C and Salazar R (2009) Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk associated with menopausal hormone therapy. Int J Cancer (in press)Google Scholar
- 28.Iwasaki M, Hamada GS, Nishimoto IN, Netto MM, Motola J Jr, Laginha FM, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Kobayashi M, Ishihara J, Yamamoto S, Hanaoka T, Tsugane S (2009) Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians. Cancer Sci 100:927–933CrossRefPubMedGoogle Scholar
- 31.Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, Vierkant RA, Maloney SD, Pankratz VS, Hillman DW, Suman VJ, Johnson J, Blake C, Tlsty T, Vachon CM, Melton LJ 3rd, Visscher DW (2005) Benign breast disease and the risk of breast cancer. N Engl J Med 353:229–237CrossRefPubMedGoogle Scholar