Top

Published in:

01-02-2009 | Original Paper

Genetic polymorphisms in the estrogen receptor beta (ESR2) gene and the risk of epithelial ovarian carcinoma

Authors: Galina Lurie, Lynne R. Wilkens, Pamela J. Thompson, Katharine E. McDuffie, Michael E. Carney, Keith Y. Terada, Marc T. Goodman

Published in: Cancer Causes & Control | Issue 1/2009

Abstract

Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence. Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case–control study included 313 women with epithelial ovarian carcinoma and 574 controls, frequency-matched on age and ethnicity. Unconditional logistic regression was used to test associations of rs1271572, rs1256030, rs1256031, and rs3020450 ESR2 genotypes with ovarian cancer risk. Compared to homozygous common allele carriers, homozygous carriers of variant alleles for rs1271572 [odds ratio (OR) = 1.79, 95% confidence interval (CI):1.15–2.79, p global = 0.01] and rs1256030 [OR = 1.67, CI: 1.08–2.59, p global = 0.04], and women with haplotypes, including variant alleles of rs1271572, rs1256030, and rs1256031 SNPs [OR = 1.75, CI: 1.17–2.63, p global = 0.007], had significantly increased risk of ovarian carcinoma. The association of the rs1271572 genotype was strongest among women who had never used contraceptive steroids (p for interaction = 0.04). Our data suggest that ESR2 might be a susceptibility marker for epithelial ovarian cancer.

Parkin DM, Whelan SL, Ferlay J, Teppo L (2002) Cancer incidence in five continents. IARC, Lyon, France

Langdon SP, Hirst GL, Miller EP et al (1994) The regulation of growth and protein expression by estrogen in vitro: a study of 8 human ovarian carcinoma cell lines. J Steroid Biochem Mol Biol 50:131–135. doi:10.1016/0960-0760(94)90019-1 PubMedCrossRef

Galtier-Dereure F, Capony F, Maudelonde T, Rochefort H (1992) Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. J Clin Endocrinol Metab 75:1497–1502. doi:10.1210/jc.75.6.1497 PubMedCrossRef

Riman T, Nilsson S, Persson IR (2004) Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand 83:783–795. doi:10.1111/j.0001-6349.2004.00550.x PubMedCrossRef

Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90:1774–1786. doi:10.1093/jnci/90.23.1774 PubMedCrossRef

Enmark E, Gustafsson JA (1999) Oestrogen receptors—an overview. J Intern Med 246:133–138. doi:10.1046/j.1365-2796.1999.00545.x PubMedCrossRef

Hillier SG, Anderson RA, Williams AR, Tetsuka M (1998) Expression of oestrogen receptor alpha and beta in cultured human ovarian surface epithelial cells. Mol Hum Reprod 4:811–815. doi:10.1093/molehr/4.8.811 PubMedCrossRef

Byers M, Kuiper GG, Gustafsson JA, Park-Sarge OK (1997) Estrogen receptor-beta mRNA expression in rat ovary: down-regulation by gonadotropins. Mol Endocrinol 11:172–182. doi:10.1210/me.11.2.172 PubMedCrossRef

Rutherford T, Brown WD, Sapi E, Aschkenazi S, Munoz A, Mor G (2000) Absence of estrogen receptor-beta expression in metastatic ovarian cancer. Obstet Gynecol 96:417–421. doi:10.1016/S0029-7844(00)00917-0 PubMedCrossRef

10.

Brandenberger AW, Tee MK, Jaffe RB (1998) Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ovarian serous cystadenocarcinoma and ovarian cancer cell lines: down-regulation of ER-beta in neoplastic tissues. J Clin Endocrinol Metab 83:1025–1028. doi:10.1210/jc.83.3.1025 PubMedCrossRef

11.

Pujol P, Rey JM, Nirde P et al (1998) Differential expression of estrogen receptor-alpha and -beta messenger RNAs as a potential marker of ovarian carcinogenesis. Cancer Res 58:5367–5373PubMed

12.

Li AJ, Baldwin RL, Karlan BY (2003) Estrogen and progesterone receptor subtype expression in normal and malignant ovarian epithelial cell cultures. Am J Obstet Gynecol 189:22–27. doi:10.1067/mob.2003.328 PubMedCrossRef

13.

Bardin A, Hoffmann P, Boulle N et al (2004) Involvement of estrogen receptor beta in ovarian carcinogenesis. Cancer Res 64:5861–5869. doi:10.1158/0008-5472.CAN-04-0552 PubMedCrossRef

14.

Park BW, Kim KS, Heo MK et al (2003) Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis? Breast Cancer Res Treat 80:79–85. doi:10.1023/A:1024406223619 PubMedCrossRef

15.

Fixemer T, Remberger K, Bonkhoff H (2003) Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate 54:79–87. doi:10.1002/pros.10171 PubMedCrossRef

16.

Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW (2000) Selective loss of estrogen receptor beta in malignant human colon. Cancer Res 60:245–248PubMed

17.

Tung KH, Goodman MT, Wu AH et al (2004) Aggregation of ovarian cancer with breast, ovarian, colorectal, and prostate cancer in first-degree relatives. Am J Epidemiol 159:750–758. doi:10.1093/aje/kwh103 PubMedCrossRef

18.

Sowers MR, Jannausch ML, McConnell DS, Kardia SR, Randolph JF Jr (2006) Menstrual cycle markers of ovarian aging and sex steroid hormone genotypes. Am J Med 119:S31–S43. doi:10.1016/j.amjmed.2006.07.004 PubMedCrossRef

19.

Peter I, Shearman AM, Vasan RS et al (2005) Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women. Am J Hypertens 18:1388–1395. doi:10.1016/j.amjhyper.2005.05.023 PubMedCrossRef

20.

Sun YH, Yang B, Wang XH et al (2005) Association between single-nucleotide polymorphisms in estrogen receptor beta gene and risk of prostate cancer. Zhonghua Wai Ke Za Zhi 43:948–951PubMed

21.

Rexrode KM, Ridker PM, Hegener HH, Buring JE, Manson JE, Zee RY (2007) Polymorphisms and haplotypes of the estrogen receptor-beta gene (ESR2) and cardiovascular disease in men and women. Clin Chem 53:1749–1756. doi:10.1373/clinchem.2007.091454 PubMedCrossRef

22.

Anonymous (1986) Surveillance, epidemiology, and end results program. Summary staging guide for the cancer surveillance, epidemiology, and end results reporting (SEER) Program. U.S. Department of Health and Human Services, Public Health Services, National Institute of Health, Bethesda, MD

23.

Oyama N, Johnson DB (1986) Hawaii health surveillance program survey methods and procedures. R & S Report No 54. State Department of Health Research and Statistics Office, Honolulu, Hawaii

24.

Tung KH, Goodman MT, Wu AH et al (2003) Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case–control study. Am J Epidemiol 158:629–638. doi:10.1093/aje/kwg177 PubMedCrossRef

25.

Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. doi:10.1093/bioinformatics/bth457 PubMedCrossRef

26.

Chen YC, Kraft P, Bretsky P et al (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 16:1973–1981. doi:10.1158/1055-9965.EPI-07-0431 PubMedCrossRef

27.

Cox DG, Bretsky P, Kraft P et al (2008) Haplotypes of the estrogen receptor beta gene and breast cancer risk. Int J Cancer 122:387–392. doi:10.1002/ijc.23127 PubMedCrossRef

28.

Pearce CL, Near AM, Butler JL et al (2008) Comprehensive evaluation of ESR2 variation and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 17:393–396. doi:10.1158/1055-9965.EPI-07-2512 CrossRef

29.

Yaffe K, Lindquist K, Sen S et al (2007) Estrogen receptor genotype and risk of cognitive impairment in elders: findings from the Health ABC study. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2007.08.003 [Available online 21 September 2007]

30.

Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P (2004) Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. Endocr Relat Cancer 11:537–551. doi:10.1677/erc.1.00800 PubMedCrossRef

31.

Cheng J, Lee EJ, Madison LD, Lazennec G (2004) Expression of estrogen receptor beta in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis. FEBS Lett 566:169–172. doi:10.1016/j.febslet.2004.04.025 PubMedCrossRef

32.

Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925–5930. doi:10.1073/pnas.93.12.5925 PubMedCrossRef

33.

Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H (2001) Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors. Cancer Res 61:2537–2541PubMed

34.

Campbell-Thompson M, Lynch IJ, Bhardwaj B (2001) Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res 61:632–640PubMed

35.

Sapi E, Brown WD, Aschkenazi S et al (2002) Regulation of Fas ligand expression by estrogen in normal ovary. J Soc Gynecol Investig 9:243–250. doi:10.1016/S1071-5576(02)00162-4 PubMedCrossRef

36.

Treeck O, Pfeiler G, Mitter D, Lattrich C, Piendl G, Ortmann O (2007) Estrogen receptor {beta}1 exerts antitumoral effects on SK-OV-3 ovarian cancer cells. J Endocrinol 193:421–433. doi:10.1677/JOE-07-0087 PubMedCrossRef

37.

Vendrell JA, Magnino F, Danis E et al (2004) Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol 32:397–414. doi:10.1677/jme.0.0320397 PubMedCrossRef

38.

Li LC, Yeh CC, Nojima D, Dahiya R (2000) Cloning and characterization of human estrogen receptor beta promoter. Biochem Biophys Res Commun 275:682–689. doi:10.1006/bbrc.2000.3363 PubMedCrossRef

39.

Hu YF, Luscher B, Admon A, Mermod N, Tjian R (1990) Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev 4:1741–1752. doi:10.1101/gad.4.10.1741 PubMedCrossRef

40.

McDonnell DP (2005) The molecular pharmacology of estrogen receptor modulators: implications for the treatment of breast cancer. Clin Cancer Res 11:871s–877sPubMed

41.

Alarid ET, Bakopoulos N, Solodin N (1999) Proteasome-mediated proteolysis of estrogen receptor: a novel component in autologous down-regulation. Mol Endocrinol 13:1522–1534. doi:10.1210/me.13.9.1522 PubMedCrossRef

42.

Bhavnani BR, Tam SP, Lu X (2008) Structure activity relationships and differential interactions and functional activity of various equine estrogens mediated via estrogen receptors ER{alpha} and ER{beta}. Endocrinology. doi:10.1210/en.2008-0304 PubMed

43.

Kuiper GG, Carlsson B, Grandien K et al (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870. doi:10.1210/en.138.3.863 PubMedCrossRef

44.

Kuiper GG, Lemmen JG, Carlsson B et al (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252–4263. doi:10.1210/en.139.10.4252 PubMedCrossRef

45.

Harris HA, Bapat AR, Gonder DS, Frail DE (2002) The ligand binding profiles of estrogen receptors alpha and beta are species dependent. Steroids 67:379–384. doi:10.1016/S0039-128X(01)00194-5 PubMedCrossRef

46.

Katzenellenbogen BS, Montano MM, Ediger TR et al (2000) Estrogen receptors: selective ligands, partners, and distinctive pharmacology. Recent Prog Horm Res 55:163–193PubMed

47.

Beral V, Bull D, Green J, Reeves G (2007) Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 369:1703–1710. doi:10.1016/S0140-6736(07)60534-0 PubMedCrossRef

48.

Sit AS, Modugno F, Weissfeld JL, Berga SL, Ness RB (2002) Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma. Gynecol Oncol 86:118–123. doi:10.1006/gyno.2002.6746 PubMedCrossRef

49.

Pike MC, Pearce CL, Peters R, Cozen W, Wan P, Wu AH (2004) Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 82:186–195PubMedCrossRef

50.

Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS (2007) Menopausal hormone therapy and risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 16:2548–2556. doi:10.1158/1055-9965.EPI-07-0550 PubMedCrossRef

Title: Genetic polymorphisms in the estrogen receptor beta (ESR2) gene and the risk of epithelial ovarian carcinoma
Authors: Galina Lurie
Lynne R. Wilkens
Pamela J. Thompson
Katharine E. McDuffie
Michael E. Carney
Keith Y. Terada
Marc T. Goodman
Publication date: 01-02-2009
Publisher: Springer Netherlands
Published in: Cancer Causes & Control / Issue 1/2009
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-008-9216-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2009

Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis

Estimating key parameters in FOBT screening for colorectal cancer

Accuracy of self-reports of Pap and mammography screening compared to medical record: a meta-analysis

Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors

Oral contraceptives and the risk of all cancers combined and site-specific cancers in Shanghai

A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women

Keynote webinar | Spotlight on antibody–drug conjugates in cancer