Estrogen may be involved in the development of prostate cancer. The association between genetic polymorphisms of estrogen receptors α (ESR1) and β (ESR2) and prostate cancer risk was examined in a nested case-control study in Washington County, Maryland. Incident prostate cancer cases (n = 269) were matched to one or two controls (n = 440) by age, sex, race, and date of blood donation. Associations between estrogen receptor genotypes or dietary intake and the development of prostate cancer were examined in conditional logistic regression models. Results from this study showed that six single base-pair polymorphisms (SNPs) of ESR1 (rs1801132, rs2077647, rs746432, rs2273206, rs851982, rs2228480) and four SNPs of ESR2 (rs4986938, rs928554, rs8018687, rs number not available for ESR2 5696 bp 3′ of STP A>G) were not significantly associated with prostate cancer risk, either by allelic or genotypic frequencies. However, an interactive association with BMI was observed in the relationship between prostate cancer risk and genotypes of ESR2 38 bp 3′ of STP G>A (rs4986938) (p = 0.031). An interaction between intake level of phytoestrogen and genotypes of ESR1 Ex1-192G>C (rs746432) and between intake level of phytoestrogen and genotypes of ESR1 Ex8+229G>A (rs2228480) and risk of prostate cancer was observed (p = 0.0009 and p = 0.044, respectively). In conclusion, selected genetic polymorphisms of ESR1 and ESR2, overall, were not associated with prostate cancer risk. However, a variation in risk by BMI and phytoestrogen intake was implicated.
References
[1]
Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (1996) Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 88: 1118–26.
[2]
Ekman P (2000) The Prostate as an endocrine organ: androgens and estrogens. Prostate 10: (Suppl)14–18.
[3]
Noble RL (1977) The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Research 37: 1929–1933.
[4]
Singer EA, Golijanin DJ, Miyamoto H, Messing EM (2008) Androgen deprivation therapy for prostate cancer. Expert Opin Pharmacother 9(2): 211–28.
[5]
Ricke WA, Wang Y, Cunha GR (2007) Steroid hormones and carcinogenesis of the prostate: the role of estrogens. Differentiation 75(9): 871–82.
[6]
Kuiper GG, Enmark E, Pelto-Huikko M (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93: 5925–5930.
[7]
Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392: 49–53.
[8]
Kuiper GG, Carlsson B, Grandien K, Enmark E, H?ggblad J, et al. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138: 863–70.
[9]
Bashirelahi N, Kneussl ES, Vassil TC, Young JD Jr, Sanefugi H, et al. (1979) Measurement and characterization of estrogen receptors in the human prostate. Prog Clin Biol Res 33: 65–84.
[10]
Prins GS, Marmer M, Woodham C, Chang W, Kuiper G, et al. (1998) Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology 139: 874–883.
[11]
Yager JD (2000) Endogenous estrogens as carcinogens through metabolic activation. J Natl Cancer Inst Monogr 27: 67–73.
[12]
Risbridger G, Wang H, Young P, Kurita T, Wang YZ, et al. (2001) Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium. Dev Biol 229: 432–442.
[13]
Fujimura T, Takahashi S, Urano T, Kumagai J, Ogushi T, et al. (2007) Increased expression of estrogen-related receptor alpha (ERR alpha) is a negative prognostic predictor in human prostate cancer. Int J Cancer 120: 2325–30.
[14]
Koehler KF, Helguero LA, Haldosén LA, Warner M, Gustafsson JA, et al. (2005) Reflections on the discovery and significance of estrogen receptor β. Endocr Rev 26: 465–478.
[15]
Signoretti S, Loda M (2001) Estrogen receptor β in prostate cancer: brake pedal or accelerator? Am J Pathol 159: 13–16.
[16]
Prins GS, Birch L, Couse JF, Choi I, Katzenellenbogen B, et al. (2001) Estrogen Imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha. Cancer Res 61: 6089–6097.
[17]
Leav I, Lau KM, Adams JY, McNeal JE, Taplin ME, et al. (2001) Comparative studies of the estrogen receptors β and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 159: 79–92.
[18]
Zhu X, Leav I, Leung YK, Wu M, Liu Q, et al. (2004) Dynamic regulation of estrogen receptor-β expression by DNA methylation during prostate cancer development and metastasis. Am J Pathol 164: 2003–2012.
[19]
Lai JS, Brown LG, True LD, Hawley SJ, Etzioni RB, et al. (2004) Metastases of prostate cancer express estrogen receptor-β. Urology 64: 814–820.
[20]
Adlercreutz H, Mazur W (1997) Phytoestrogens and Western diseases. Ann Med 29: 95–120.
[21]
Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, et al. (2003) Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev 12(7): 665–8.
[22]
Tanaka Y, Sasaki M, Kaneuchi M, Shiina H, Igawa M, et al. (2003) Polymorphisms of estrogen receptor alpha in prostate cancer. Mol Carcinog 37(4): 202–8.
[23]
Suzuki K, Nakazato H, Matsui H, Koike H, Okugi H, et al. (2003) Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol-O-methyltransferase are associated with familial prostate carcinoma risk in a Japanese population. Cancer 98(7): 1411–6.
[24]
Low YL, Taylor JI, Grace PB, Mulligan AA, Welch AA, et al. (2006) Phytoestrogen exposure, polymorphisms in COMT, CYP19, ESR1, and SHBG genes, and their associations with prostate cancer risk. Nutr Cancer 56(1): 31–9.
[25]
Sobti RC, Gupta L, Singh SK, Seth A, Kaur P, et al. (2008) Role of hormonal genes and risk of prostate cancer: gene-gene interactions in a North Indian population. Cancer Genet Cytogenet 185(2): 78–85.
[26]
Hernández J, Balic I, Johnson-Pais TL, Higgins BA, Torkko KC, et al. (2006) Association between an estrogen receptor alpha gene polymorphism and the risk of prostate cancer in black men. J Urol 175(2): 523–7.
[27]
Modugno F, Weissfeld JL, Trump DL, Zmuda JM, Shea P (2001) et al. Allelic Varients of Aromatase and Androgen and Estrogen Receptors: Toward a Multigenetic Model of Prostate Cancer Risk. Clinical Cancer Research 7: 3092–3096.
[28]
Cancel-Tassin G, Latil A, Rousseau F, Mangin P, Bottius E, et al. (2003) Association study of polymorphisms in the human estrogen receptor alpha gene and prostate cancer risk. Eur Urol 44(4): 487–90.
[29]
Nicolaiew N, Cancel-Tassin G, Azzouzi AR, Legrand B, Mangin P, et al. (2008) Association between estrogen and androgen receptor genes and prostate cancer risk. Eur J Endocrinol. doi:10.1530/EJE-08-0321.
[30]
Cunningham JM, Hebbring SJ, McDonnell SK, et al. (2007) Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. Cancer Epidemiol Biomarkers Prev 16(5): 969–78.
[31]
McIntyre MH, Kantoff PW, Stampfer MJ, et al. (2007) Prostate cancer risk and ESR1 TA, ESR2 CA repeat polymorphisms. Cancer Epidemiol Biomarkers Prev 16(11): 2233–6.
[32]
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(14): 948–51.
[33]
Thellenberg-Karlsson C, Lindstrom S, Malmer B, et al. (2006) Estrogen receptor beta polymorphism is associated with prostate cancer risk. Clin Cancer Res 15: 306–11.
[34]
Hedelin M, Balter KA, Chang ET, et al. (2006) Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer. Prostate 66(14): 1512–20.
[35]
Schneider G, Kirschner MA, Berkowitz R, et al. (1979) Increased estrogen production in obese men. J Clin Endocrinol Metab 48: 633–638.
[36]
Kuiper GG, Gustafsson JA (1997) The novel estrogen receptor-β subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens. FEBS Lett 410: 87–90.
[37]
The George WComstock Center for Public Health Research and Prevention [homepage on the Internet]. Maryland: 2002, The Johns Hopkins Bloomberg School of Public Health [updated 2002; cited 2008 Feb 28]. Available from: .
[38]
Packer BR, Yeager M, Staats B, et al. SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes. Nucleic Acids Res 2004; 32(Database issue): D528–D532.
[39]
den Dunnen JT, Antonarakis SE (2001) Nomenclature for the description of human sequence variations. Hum Genet 109(1): 121–124.
[40]
USDA-Iowa State University Database on the Isoflavone Content of Foods [homepage on the Internet]. U.S. Department of Agriculture, Agricultural Research Service. [updated 2004 Oct 25; cited 2008 Feb 28]. Available from .
[41]
Southey MC, Batten LE, McCredie MR, et al. (1998) Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty. J Natl Cancer Inst 90(7): 532–6.
[42]
Medeiros R, Vasconcelos A, Costa S, et al. (2003) Steroid hormone genotypes ARStuI and ER325 are linked to the progression of human prostate cancer. Cancer Genet Cytogenet 141(2): 91–6.
[43]
Lagakos SW (2006) Challenges of subgroup analysis. N Engl J Med 354(16): 1667–1668.
[44]
Huang HY, Alberg AJ, Norkus EP, et al. (2003) Prospective Study of Antioxidant Micronutrients in the Blood and the Risk of Developing Prostate Cancer. Am J Epidemiol 157: 335–344.