© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 23, 1807-1808,
December 4, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
Re: Population-Based, Case–Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk
Affiliations of authors: A. Hishida, (Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan, and the Department of Molecular Medicine and Clinical Science, Nagoya University Graduate School of Medicine, Nagoya), N. Hamajima, K. Matsuo, K. Hirose, K. Tajima, Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya; N. Emi, Department of Molecular Medicine and Clinical Science, Nagoya University Graduate School of Medicine, Nagoya; H. Iwata, Department of Breast Surgery, Aichi Cancer Center, Nagoya.
Correspondence to: Asahi Hishida, M.D., Department of Molecular Medicine and Clinical Science, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466–8550, Japan (e-mail: a-hishi{at}med.nagoya-u.ac.jp).
HER2 is a well-known proto-oncogene encoding a transmembrane glycoprotein with tyrosine kinase activity. This protein is reported to have prognostic and predictive roles in breast cancer, and it is supposed to be involved with early pathogenesis of breast cancer. A polymorphism at codon 655 (Ile to Val; Ile655Val) in the transmembrane domain region of this gene was identified; a recent population-based case–control study in Shanghai, China (1), revealed that women with the Ile/Val or Val/Val genotype had an elevated risk for breast cancer and that among women with the Val/Val genotype the risk was even more elevated. Subsequently, Ameyaw et al. (2) reported that the distribution of this HER2 polymorphism (Val655Ile) varied considerably between ethnic groups, with the Val655 allele detected in 20% of the Caucasians examined but absent in an African population. Afterward, several studies (3–6) were conducted on the association between the HER2 Val655Ile polymorphism and the risk of breast cancer among Caucasians, Africans, and Latinos, but no statistically significant association was observed. However, the possibility that a marked association could be observed in Asian populations was not ruled out.
We have genotyped 420 women enrolled in a hospital-based prevalent case–control study at Aichi Cancer Center Hospital (236 case patients and 184 control subjects) to investigate the association between the HER2 Val655Ile polymorphism and the risk of breast cancer in Japanese women. We also genotyped an HER2 A-to-G polymorphism (A23275G, where the positions are numbered from the translation initiation site; Genbank accession no. AC087491) at the intron just 3' to the transmembrane coding region reported by Briscoe et al. (7) for the same subjects.
The genotype frequencies of the two polymorphisms for the case patients and control subjects and the age-adjusted odds ratios (ORs) for HER2 Val655Ile and A-to-G polymorphisms are shown in Table 1
. Women with the Val/Val genotype demonstrated a statistically nonsignificant reduced risk of breast cancer (OR = 0.31, 95% confidence interval [CI] = 0.08 to 1.24). As for the HER2 A-to-G polymorphism, neither women with the AA genotype nor women with the AG genotype demonstrated a statistically significant OR compared with the women having GG genotype.
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The genotype frequency of the HER2 Val655 allele in our Japanese control subjects (14.9%) was not statistically significantly different from that of the Chinese control subjects reported on by Xie et al. (11.1%) (1), suggesting that genetic backgrounds of Japanese populations are similar to those of Chinese populations. Xie et al. reported that women with the Val/Val genotype had a statistically significantly elevated risk of breast cancer compared with women with the Ile/Ile genotype; however, our study results demonstrated no marked association. These contradictory results might be partially attributable to the small number of subjects with the Val/Val genotype of HER2 Val655Ile polymorphism in both studies, leading to a decreased statistical power of these studies to detect such differences. Another possibility is that the contribution of the gene polymorphism to the cancer etiology differs even between Japanese and Chinese, influenced by gene–gene interactions and gene–environment interactions.
In conclusion, the association between HER2 Val655 and the risk of breast cancer was not observed in Japanese women in our study. This finding supports the recent reports (3–6) that found no association among patients with breast cancer and HER2 polymorphisms. Nevertheless, it still remains unclear whether the findings made by Xie et al. (1) were a true ethnic variation in the penetrance of the Val655 allele. Further studies with sufficiently larger populations are needed to elucidate this association.
NOTES
Editor’s note: Xie et al. declined to respond.
References
1 Xie D, Shu XO, Deng Z, Wen WQ, Creek KE, Dai Q, et al. Population-based, case–control study of HER-2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2000;92:412–7.
2 Ameyaw MM, Thornton N, McLeod H, Population-based, case–control study of HER-2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2000;92:1947.
3 Baxter SW, Campbell IG. Population-based, case–control study of HER-2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2001;93:557–9.
4 Wang-Gohrke S, Chang-Claude J. Population-based, case–control study of HER-2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2001;93:1657–8.
5 Keshava C, McCanlies EC, Keshava N, Wolff MS, Weston A. Distribution of HER2V655 genotypes in breast cancer cases and controls in the United States. Cancer Lett 2001;173:37–41.[CrossRef][ISI][Medline]
6 Zheng W, Kataoka N, Xie D, Young SR. Population-based, case–control study of HER-2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2001;93:558–9.
7 Briscoe WT, Ray DB, Airhart JL, Ratliff AL, Shockley EA, Whetsell L. A new high frequency polymorphism in the HER-2/neu oncogene in normal tissue and breast tumors. Breast Cancer Res Treat 1993;28:45–9.[Medline]
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