Estrogen receptor-α polymorphism in a Taiwanese clinical breast cancer population: a case–control study

Breast Cancer Research

Pin-Wen Lin¹  Shoei-Loong Lin²  Kung-Chia Young³  Wei-Chiang Hsiao¹ 

[1] Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China;Department of Surgery, Tainan Hospital, Department of Health, Tainan, Taiwan, Republic of China;Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China

关键词: polymorphism;    metastasis;    lymph node;    estrogen receptor-α;   

 received in 2003-10-21, accepted in 2004-01-29,  发布年份 2004

【 摘 要 】

Introduction

Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-α polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age–incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-α in either population is therefore of value in the clinical setting for that ethnic group.

Methods

A case–control study was conducted to establish a database of ER-α polymorphisms in a Taiwanese population in order to compare Western and Taiwanese (Asian) distributions and to evaluate ER-α polymorphism as an indicator of clinical outcome. The ER-α gene was scanned in a Taiwanese clinical breast cancer group (189 patients) and in healthy individuals (177 healthy control individuals). PCR single-strand conformation polymorphism technology was employed and real-time PCR melting curve analysis was performed.

Results

Three sites of silent single nucleotide polymorphism (SNPs) were found, as reported previously in Western studies, but at significantly different frequencies. Among the three SNPs, the frequency of allele 1 (TCT → TCC) in codon 10 was significantly lower in breast cancer patients (32.0%) than in control individuals (40.4%; P = 0.018). We found that allele 1 (ACG → ACA) in codon 594 was less common in breast cancer patients with a family history of breast cancer (5.9%) than in those without such a history (19.6%; P = 0.049). Individually, both allele 1 in codon 325 (CCC → CCG) and allele 1 in codon 594 exhibited a reverse association with the occurrence of lymph node metastasis. Furthermore, incorporation of both SNP markers further increased predictive accuracy.

Conclusions

Our data suggest that ER-α polymorphisms are correlated with various aspects of breast cancer in Taiwan. ER-α genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting breast cancer lymph node metastasis.

【 授权许可】

   
2004 Hsiao et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 参考文献 】

• [1]Brinton L, Lacey J, Devesa SS: Epidemiology of Breast Cancer. In Cancer of the Breast. 5th edition. Edited by Donegan WL, Spratt JS. Philadelphia: WB Saunders; 2002:111-132.
• [2]Anonymous: Cancer Registry Annual Report in Taiwan Area 1995. Department of Health, Executive Yuan, ROC; 1998:48-49.
• [3]Yang PS, Yang TL, Liu CL, Wu CW, Shen CY: A case–control study of breast cancer in Taiwan: a low-incidence area. Br J Cancer 1997, 75:752-756.
• [4]Chen CJ, You SL, Lin LH, Hsu WL, Yang YW: Cancer epidemiology and control in Taiwan: a brief review. Jpn J Clin Oncol 2002, Suppl:S66-S81.
• [5]Cheng SH, Tsou MH, Liu MC, Jian JJ, Cheng JC, Leu SY, Hsieh CY, Huang AT: Unique features of breast cancer in Taiwan. Breast Cancer Res Treat 2000, 63:213-223.
• [6]Anderson E, Clarke RB, Howell A: Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia 1998, 3:23-35.
• [7]Anderson E: The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Breast Cancer Res 2002, 4:197-201. BioMed Central Full Text
• [8]Key TJ, Pike MC: The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 1988, 24:29-43.
• [9]Ravdin PM, Green S, Dorr TM, McGuire WL, Fabian C, Pugh RP, Carter RD, Rivkin SE, Borst JR, Belt RJ, Metch B, Osborne CK: Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. J Clin Oncol 1992, 10:1284-1291.
• [10]Clarke RB, Howell A, Potten CS, Anderson E: Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 1997, 57:4987-4991.
• [11]Roodi N, Bailey LR, Kao WY, Verrier CS, Yee CJ, Dupont WD, Parl FF: Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst 1995, 87:446-451.
• [12]Iwase H, Greenman JM, Barnes DM, Hodgson S, Bobrow L, Mathew CG: Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors. Cancer Lett 1996, 108:179-184.
• [13]Curran JE, Lea RA, Rutherford S, Weinstein SR, Griffiths LR: Association of estrogen receptor and glucocorticoid receptor gene polymorphisms with sporadic breast cancer. Int J Cancer 2001, 95:271-275.
• [14]Vasconcelos A, Medeiros R, Veiga I, Pereira D, Carrilho S, Palmeira C, Azevedo C, Lopes CS: Analysis of estrogen receptor polymorphism in codon 325 by PCR-SSCP in breast cancer: association with lymph node metastasis. Breast J 2002, 8:226-229.
• [15]Southey MC, Batten LE, McCredie MR, Giles GG, Dite G, Hopper JL, Venter DJ: Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty. J Natl Cancer Inst 1998, 90:532-536.
• [16]Kang HJ, Kim SW, Kim HJ, Ahn SJ, Bae JY, Park SK, Kang D, Hirvonen A, Choe KJ, Noh DY: Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk. Cancer Lett 2002, 178:175-180.
• [17]Murphy LC, Dotzlaw H, Leygue E, Douglas D, Coutts A, Watson PH: Estrogen receptor variants and mutations. J Steroid Biochem Mol Biol 1997, 62:363-372.
• [18]Fisher ER, Anderson S, Redmond C, Fisher B: Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants. Cancer 1993, 71:2507-2514.
• [19]Henson DE, Ries L, Freedman LS, Carriaga M: Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer 1991, 68:2142-2149.
• [20]Canavese G, Catturich A, Vecchio C, Tomei D, Gipponi M, Bruzzi P, Badellino F: Prognostic role of lymph-node level involvement in patients undergoing axillary dissection for breast cancer. Eur J Surg Oncol 1998, 24:104-109.
• [21]Goldhirsch A, Wood WC, Senn HJ, Glick JH, Gelber RD: Meeting highlights: international consensus panel on the treatment of primary breast cancer. J Natl Cancer Inst 1995, 87:1441-1445.
• [22]Carter CL, Allen C, Henson DE: Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989, 63:181-187.