CORRESPONDENCE

RESPONSE: Re: Population-Based, Case–Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk

Wei Zheng, Wan-Qing Wen

Affiliation of authors: Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.

Correspondence and reprint requests to: Wei Zheng, M.D., Ph.D., Vanderbilt University Medical Center, Center for Health Services Research, Medical Center East, 6th floor, Nashville, TN 37232–8300.

We read with interest the letter by Drs. Wang-Gohrke and Chang-Claude regarding the association between a HER2 genetic polymorphism and breast cancer risk. In a case–control study conducted among German Caucasian women, Drs. Wang-Gohrke and Chang-Claude found that the Val allele of the HER2 (Val655Ile) polymorphism was associated with a twofold elevated risk of breast cancer among women who had a family history of breast cancer among their first-degree relatives. This positive association, however, was not observed among women without such a family history. These data suggest that a family history of breast cancer may modify the association between the HER2 polymorphism and the risk of breast cancer.

We reported previously that this HER2 polymorphism may be associated with an elevated risk of breast cancer among Chinese women (1) but not among Caucasian women (2). To follow the suggestion of Drs. Wang-Gohrke and Chang-Claude, we reanalyzed our data stratified by family history of breast cancer (Table 1Go). Only about 3% of the subjects in the Shanghai study had a family history of breast cancer, and thus the analysis among this group of women was not informative. In the Iowa study, among women with a family history of breast cancer, the frequency of the Val allele was slightly higher in case patients (48%) than that in control subjects (45%). On the other hand, among women without a family history of breast cancer, the frequency of this allele was slightly lower in case patients (40%) than in control subjects (43%). Although our data appear to be in line with the results reported by Drs. Wang-Gohrke and Chang-Claude, the odds ratio observed in our study among women with a family history of breast cancer was not statistically significant. However, the sample size in our study was small and the Iowa study was restricted to postmenopausal women.


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Table 1. Case–control analysis of the HER2 (Val655 Ile) polymorphism in relation to the risk of breast cancer among Chinese and Caucasian women
 
As discussed in our previous reports (1,2), a type I statistical error may be a concern for any association studies of genetic polymorphisms with disease risk, particularly when the functional importance of the polymorphism under study is unknown. Although we have shown in a small case–case study that the HER2 (Val655Ile) polymorphism may be associated with the amplification of this oncogene (2), that study did not directly address the functional importance of this polymorphism. We concur with Drs. Wang-Gohrke and Chang-Claude that further studies are needed to elucidate the association of HER2 polymorphisms with the risk of breast cancer.

REFERENCES

1 Xie D, Shu XO, Deng Z, Wen WQ, Creek KE, Dia Q, et al. Population-based, case–control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 2000;92:412–7.[Abstract/Free Full Text]

2 Zheng W, Kataoka N, Xie W, Young SR. Response: Re: population-based, case–control study of HER2 genetic polymorphism and breast cancer risk [letter]. J Natl Cancer Inst 2001;93:558–9.[Free Full Text]



             
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