Affiliations of authors: K. Y. K. Chan, A. N. Y. Cheung, T. W. Lai, U.-S. Khoo Department of Pathology, The University of Hong Kong, Hong Kong; H. H. Ko, Department of Pathology, The University of Hong Kong, and Pacific Bridge Project, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; S. P. Yip, Biomedical Science Section, School of Nursing, The Hong Kong Polytechnic University, Hong Kong.
Correspondence to: Ui-Soon Khoo, F.R.C.Path. (U.K.), Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Rd., Hong Kong (e-mail: uskhoo{at}pathology.hku.hk).
Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene encoding a transmembrane glycoprotein with tyrosine kinase activity. The amplification and overexpression of this gene have been observed in breast and ovarian cancers and are associated with the response of breast cancers to chemotherapy. A single nucleotide polymorphism (SNP) at codon 655 resulting in a valine to isoleucine change (Val655Ile) was reported in the Journal (1) to be associated with an increased risk of breast cancer among women in Shanghai, China. The frequency of the valine allele varies among ethnic groups. The valine allele has a frequency of 20% in Caucasians and 24% in African-Americans but was not detected in an African population (2). Studies among British (3) and GermanCaucasian (4) populations showed that the valine allele was not associated with a higher risk for breast or ovarian cancer.
Because genetic heterogeneity exists among individuals from different geographical regions of China (5,6), we investigated the frequency of the Val655Ile HER2 polymorphism in a southern Chinese-based age-matched casecontrol study in Hong Kong to determine whether it is associated with risk for ovarian cancer in this population.
Paraffin-embedded tissue blocks were retrieved from the files of the Department of Pathology, Queen Mary Hospital, a major referral center in Hong Kong for patients with gynecologic malignancies. Nontumor blocks were obtained from 205 Chinese women diagnosed with primary epithelial ovarian carcinoma and from 205 age-matched control subjects. Control subjects had undergone total hysterectomy for a benign condition and did not have ovarian cancer. The mean age of both groups was 50 years. The Val655Ile polymorphism was detected by restriction fragment length polymorphism as described (1) except that the primers were 5'-ATCCCTGACCCTGGCTTCC-3' (forward) and 5'-CGCTTGATGAGGATCCCAAA-3' (reverse). Statistical analysis was performed with a two-sided 2 test to compare the allele and genotype frequencies in the studied sample with those reported in ethnic control populations.
We did not detect a valine/valine homozygote among the 410 subjects studied. The valine allele frequency found in normal control subjects was similar to that reported in the Shanghai population (1) but was statistically significantly different (P<.001) from those in other ethnic group studies (24). Both the valine allele frequency and the genotype frequency were statistically significantly different between patients with ovarian cancer and normal control subjects (P = .022 and .016, respectively). The genotypes were in HardyWeinberg equilibrium in both cancer and control groups. Heterozygote valine allele carriers had a statistically significantly decreased risk for ovarian cancer compared with homozygote isoleucine allele carriers (2 = 5.831; 1 df; P = .016; odds ratio = 0.517, 95% confidence interval = 0.310 to 0.865). These results differ from those for breast cancer reported by Xie et al. (1) and those in a British population in which the valine allele was not associated with breast or ovarian cancer risk (3) (Table 1
).
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REFERENCES
1 Xie D, Shu XO, Deng Z, Wen WQ, Creek KE, Dai Q et al. Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2000;92:4127.
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4 Wang-Gohrke S, Chang-Claude J. Re: Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2001;93:16579.
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6 Khoo US, Chan KY, Cheung AN, Xue WC, Shen DH, Fung KY et al. Recurrent BRCA1 and BRCA2 germline mutations in ovarian cancer: a founder mutation of BRCA1 identified in the Chinese population. Hum Mutat 2002;19:3078.
7 Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM et al. A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev 2001;10:95560.
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