Affiliation of authors: Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen, U.K.
Correspondence to present address: Howard L. McLeod, D.Pharm., Department of Medicine, Division of Oncology, Washington University Medical School, Rm. 1021 CSRB NT, 660 S. Euclid Ave., Campus Box 8069, St. Louis, MO 631101093 (e-mail: hmcleod{at}imgate.wustl.edu).
Altered expression of the protooncogene HER2 (also known as c-erbB-2) gene has been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors (1,2). It is also a cancer therapeutic target, with antibody-based therapy against the Her2 protein, and a predictive marker for response to breast cancer chemotherapy (3,4).
A single nucleotide polymorphism (SNP) at codon 655, resulting in a guanine to adenine transition (Val655Ile) in the transmembrane domain-coding region of this gene, was identified previously (5). A population-based, casecontrol study of this polymorphism was reported recently in the Journal (6), and the Val allele was found to be associated with an increased risk of breast cancer, particularly among younger women. However, there is little information on the population distribution of this SNP. This is an important issue in the context of statistically significant ethnic differences in the incidence of breast cancer and of other solid tumors (7).
We evaluated this polymorphism in 257 Caucasian, 90 African-American, and 200 African (Ghanaian) healthy blood donors. Genotyping of the guanine to adenine polymorphism at codon 655 of the HER2 gene was done with the previously described polymerase chain reactionrestriction fragment length polymorphism assay (5,6). Comparison was made between allele frequencies and genotype frequencies for the Caucasian, African-American, and African populations and the Chinese control population described previously by Xie et al. (6), with the use of the chi-squared test.
The Val allele was not detected among the 400 alleles evaluated in the African population (Table 1). In contrast, the Val allele was found in 20% of Caucasian alleles, in 24% of African-American alleles, and in 11% of Chinese alleles. The homozygous Val/Val genotype associated with an increased risk of breast cancer was observed more frequently in Caucasian subjects (5.4%) and African-American subjects (4.4%) than in Chinese subjects (0.3%) (P = .01) (Table 1
). The HER2 allele frequency was not significantly different between African-American and Caucasian subjects (P = .49). The genotype frequency was not statistically significantly different from that expected from the HardyWeinberg equilibrium in any population.
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Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, et al. ErbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst 1998;90:136170.
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McNeil C. Herceptin raises its sights beyond advanced breast cancer [news]. J Natl Cancer Inst 1998;90:8823.
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6
Xie D, Shu XO, Deng Z, Wen WQ, Creek KE, Dai Q, et al. Population-based, casecontrol study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2000;92:4127.
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