© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 23, 1947,
December 6, 2000
© 2000 Oxford University Press
CORRESPONDENCE |
Re: Population-Based, Case–Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk
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 63110–1093 (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, case–control 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 reaction–restriction 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 Hardy–Weinberg equilibrium in any population.
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The results help interpret the implications of HER2 SNP for disease risk and treatment response in different ethnic groups. The data suggest that this SNP has variable frequency in different ethnic groups. In addition, intraracial differences in allele frequency were seen. The presence of the Val allele in the African-American population, but not in the African population, is consistent with the genetic mixing, which has been identified through historical and molecular analysis. However, the presence of many first-generation immigrant populations in the United States provides warning for the overinterpretation of results from any one ethnic group. Therefore, the usefulness of the HER2 SNP in the determination of risk, prognosis, and treatment response of breast cancer will be dramatically different between ethnic populations.
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