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Estrogen Receptor Alpha Gene Polymorphisms and Breast Cancer Risk: a Case-control Study with Meta-analysis Combined

  • Lu, Hong (Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University) ;
  • Chen, Dong (Wenzhou Center of Disease Control and Prevention) ;
  • Hu, Li-Ping (Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University) ;
  • Zhou, Lian-Lian (Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University) ;
  • Xu, Hui-Ying (Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University) ;
  • Bai, Yong-Heng (Wenzhou Key Laboratory of Surgery, First Affiliated Hospital of Wenzhou Medical University) ;
  • Lin, Xiang-Yang (Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University)
  • Published : 2013.11.30

Abstract

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-${\alpha}$) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-${\alpha}$ gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-${\alpha}$ polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location.

Keywords

Estrogen receptor;polymorphism;breast cancer;risk;meta-analysis

References

  1. American Cancer Society. Cancer Facts and Figures 2011. [Available online at: http://www.cancer.org/docroot/home/index.asp]
  2. Andersen TI, Heimdal KR, Skrede M, et al (1994). Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. Hum Genet, 94, 665-70.
  3. Bocchinfuso WP, Lindzey JK, Hewitt SC, et al (2000). Induction of mammary gland development in estrogen receptor-alpha knockout mice. Endocrinology, 141, 2982-94. https://doi.org/10.1210/endo.141.8.7609
  4. Cai Q, Shu XO, Jin F, et al (2003). Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev, 12, 853-9.
  5. Crooke PS, Justenhoven C, Brauch H, et al (2011). Estrogen Metabolism and Exposure in a Genotypic-Phenotypic Model for Breast Cancer Risk Prediction. Cancer Epidemiol Biomarkers Prev, 20, 1502-15. https://doi.org/10.1158/1055-9965.EPI-11-0060
  6. DerSimonian R, Kacker R (2007). Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials, 28, 105-14. https://doi.org/10.1016/j.cct.2006.04.004
  7. Dotzlaw H, Alkhalaf M, Murphy LC (1992). Characterization of estrogen receptor variant mRNAs from human breast cancers. Mol Endocrinol, 6, 773-85.
  8. Dunning AM, Healey CS, Baynes C, et al (2009). Association of ESR1 gene tagging SNPs with breast cancer risk. Hum Mol Genet, 18, 1131-9. https://doi.org/10.1093/hmg/ddn429
  9. Egger M, Juni P, Bartlett C, et al (2003). How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technol Assess, 7, 1-76.
  10. Fuqua SA, Fitzgerald SD, Allred DC, et al (1992). Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors. Cancer Res, 52, 483-6.
  11. Gonzalez-Mancha R, Galan JJ, Crespo C, et al (2008). Analysis of the ERalpha germline PvuII marker in breast cancer risk. Med Sci Monit, 14, CR136-43.
  12. Gonzalez-Zuloeta Ladd AM, Vasquez AA, Rivadeneira F, et al (2008). Estrogen receptor alpha polymorphisms and postmenopausal breast cancer risk. Breast Cancer Res Treat, 107, 415-9. https://doi.org/10.1007/s10549-007-9562-3
  13. Herrington DM, Howard TD, Brosnihan KB, et al (2002). Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation, 105, 1879-82. https://doi.org/10.1161/01.CIR.0000016173.98826.88
  14. Hu Z, Song CG, Lu JS, et al (2007). A multigenic study on breast cancer risk associated with genetic polymorphisms of ER Alpha, COMT and CYP19 gene in BRCA1/BRCA2 negative Shanghai women with early onset breast cancer or affected relatives. J Cancer Res Clin Oncol, 133, 969-78. https://doi.org/10.1007/s00432-007-0244-7
  15. Key T, Appleby P, Barnes I, et al (2002). Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst, 94, 606-16. https://doi.org/10.1093/jnci/94.8.606
  16. Kjaergaard AD, Ellervik C, Tybjaerg-Hansen A, et al (2007). Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysis. Circulation, 115, 861-71. https://doi.org/10.1161/CIRCULATIONAHA.106.615567
  17. Kobayashi S, Inoue S, Hosoi T, et al (1996). Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res, 11, 306-11.
  18. Li Z, Zhang Z, He Z, et al (2009). A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn). Cell Res, 19, 519-23. https://doi.org/10.1038/cr.2009.33
  19. Little J, Bradley L, Bray MS, et al (2002). Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am J Epidemiol, 156, 300-10. https://doi.org/10.1093/oxfordjournals.aje.a000179
  20. Liu W, Konduri SD, Bansal S, et al (2006). Estrogen receptor-alpha binds p53 tumor suppressor protein directly and represses its function. J Biol Chem, 281, 9837-40. https://doi.org/10.1074/jbc.C600001200
  21. Lu X, Li B, Wei JM, et al (2005). [The XbaI and PvuII gene polymorphisms of the estrogen receptor alpha gene in Chinese women with breast cancer]. Zhonghua Wai Ke Za Zhi, 43, 290-3.
  22. Mallepell S, Krust A, Chambon P, et al (2006). Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A, 103, 2196-201. https://doi.org/10.1073/pnas.0510974103
  23. Medina D, Sivaraman L, Hilsenbeck SG, et al (2001). Mechanisms of hormonal prevention of breast cancer. Ann N Y Acad Sci, 952, 23-35. https://doi.org/10.1111/j.1749-6632.2001.tb02725.x
  24. Onland-Moret NC, van Gils CH, Roest M, et al (2005). The estrogen receptor alpha gene and breast cancer risk (The Netherlands). Cancer Causes Control, 16, 1195-202. https://doi.org/10.1007/s10552-005-0307-5
  25. Oxman AD, Guyatt GH (1993). The science of reviewing research. Ann N Y Acad Sci, 703, 125-33; discussion 33-4. https://doi.org/10.1111/j.1749-6632.1993.tb26342.x
  26. Rasti M, Arabsolghar R, Khatooni Z, et al (2012). p53 Binds to estrogen receptor 1 promoter in human breast cancer cells. Pathol Oncol Res, 18, 169-75. https://doi.org/10.1007/s12253-011-9423-6
  27. Roodi N, Bailey LR, Kao WY, et al (1995). Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst, 87, 446-51. https://doi.org/10.1093/jnci/87.6.446
  28. Russo IH, Russo J (1998). Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia, 3, 49-61. https://doi.org/10.1023/A:1018770218022
  29. Shen Y, Li DK, Wu J, et al (2006). Joint effects of the CYP1A1 MspI, ERalpha PvuII, and ERalpha XbaI polymorphisms on the risk of breast cancer: results from a population-based case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev, 15, 342-7. https://doi.org/10.1158/1055-9965.EPI-05-0485
  30. Shi YY, He L (2005). SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res, 15, 97-8. https://doi.org/10.1038/sj.cr.7290272
  31. Shin A, Kang D, Nishio H, et al (2003). Estrogen receptor alpha gene polymorphisms and breast cancer risk. Breast Cancer Res Treat, 80, 127-31. https://doi.org/10.1023/A:1024439202528
  32. Smigal C, Jemal A, Ward E, et al (2006). Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin, 56, 168-83. https://doi.org/10.3322/canjclin.56.3.168
  33. Wedren S, Lovmar L, Humphreys K, et al (2004). Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study. Breast Cancer Res, 6, R437-49. https://doi.org/10.1186/bcr811
  34. Weiderpass E, Persson I, Melhus H, et al (2000). Estrogen receptor alpha gene polymorphisms and endometrial cancer risk. Carcinogenesis, 21, 623-7. https://doi.org/10.1093/carcin/21.4.623
  35. Yaich L, Dupont WD, Cavener DR, et al (1992). Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood. Cancer Res, 52, 77-83.

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