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Japanese Journal of Clinical Oncology Advance Access published online on September 26, 2008
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyn097
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© The Author (2008). Published by Oxford University Press. All rights reserved

Possible Difference in Frequencies of Genetic Polymorphisms of Estrogen Receptor {alpha}, Estrogen Metabolism and P53 Genes Between Estrogen Receptor-positive and -negative Breast Cancers

Maho Hamaguchi, Mariko Nishio, Tatsuya Toyama, Hiroshi Sugiura, Naoto Kondo, Yoshitaka Fujii and Hiroko Yamashita

Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

For reprints and all correspondence: Hiroko Yamashita, Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Mizuho-ku, Nagoya 467-8601, Japan. E-mail: hirokoy{at}med.nagoya-cu.ac.jp

Received April 28, 2008; accepted August 21, 2008

Objective: Genetic polymorphisms associated with breast cancer risk are likely to differ among ethnic and molecular subtypes. The ability to identify genetic polymorphisms affecting the risk of estrogen receptor (ER)-positive breast cancer may lead to the more efficient selection of candidates for chemoprevention with endocrine agents. We focused on identifying common genotypes for ER-positive breast cancer in premenopausal Japanese women.

Methods: We compared genetic polymorphisms of ER{alpha}, estrogen metabolism genes (CYP17A1, CYP19A1, HSD17B1 COASY, CYP1B1 and COMT), and p53 between ER-positive and -negative female Japanese breast cancer patients, and analyzed whether these polymorphisms affected the frequency of ER-positive breast cancer.

Results: Carriers of the G allele of ER{alpha} (rs6905370) were more frequent in ER-positive breast cancer than in ER-negative breast cancer especially in those under 50-year old. Pairwise analysis showed that combinations of the ER{alpha} G allele with the homozygous Trp genotype of CYP19A1 codon 39 (rs2236722), the methionine (Met) allele of COMT codon 158 (rs4680) or Pro allele of p53 codon 72 (rs1042522) were more frequent in ER-positive than ER-negative breast cancer, especially in patients less than 50-year old. The frequencies of these combinations were even higher in patients with strongly ER-positive tumors (Allred's scores of 7 or 8).

Conclusion: Our study demonstrated genetic polymorphisms of ER{alpha}, CYP19A1, COMT and p53 genes frequently occur in ER-positive breast cancer in premenopausal Japanese women.

Key Words: breast cancer • genetic polymorphisms • estrogen receptor


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