© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 21, 1657,
November 7, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
Re: Population-Based, Case–Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk
Affiliations of authors: S. Wang-Gohrke, Molecular Biology Laboratory, Department of Obstetrics and Gynecology, University of Ulm, Germany; J. Chang-Claude, Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Correspondence regarding molecular biology: Shan Wang-Gohrke, M.D., Molecular Biology Laboratory, Department of Obstetrics and Gynecology, University of Ulm, Prittwitzstrasse 43, D-89075 Ulm, Germany (e-mail: shan.wang{at}medizin.uni-ulm.de).Correspondence regarding epidemiology: Jenny Chang-Claude, Ph.D., Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Postfach 101949, 69009 Heidelberg, Germany (e-mail: J.Chang-Claude{at}dkfz.de).
A valine-to-isoleucine polymorphism at codon 655 (Val655Ile) was first reported in the Journal (1) to be associated with an increased risk of breast cancer in a population-based, case–control study among a Han Chinese population. The distribution of the polymorphism, however, was found to vary considerably between ethnic groups (2). Baxter and Campbell (3) then reported that genotype frequencies of HER2 Val655Ile were similar between case patients and control subjects in a hospital-based, case– control study among British women younger than 40 years. This observation raises the question of whether the association reported by Xie et al. reflects a true ethnic variation in the penetrance of the valine allele or a type I statistical error.
We used a large population-based 1 : 2 age-matched case–control study among German Caucasian women to determine whether the polymorphism of the HER2 Val655Ile polymorphism alters the risk for breast cancer by the age of 50 years. We also investigated whether this polymorphism interacts with other risk factors previously shown to be related to breast cancer in the study. As described previously (4), patients were diagnosed with incident in situ or invasive breast cancer before 51 years of age, and two control subjects per case patient matched by exact age and study region were selected from random lists of residents supplied by the population registries. The study was reviewed by the ethics committee of the University of Heidelberg. Overall, 706 (70% of eligible) case patients and 1381 (61% of eligible) population control subjects participated. This analysis is restricted to 615 case patients and 1078 control subjects who also provided a blood sample and have at least one parent of German nationality. The mean ages of case patients and control subjects were 42.5 and 42.6 years, respectively. With the size of this study, we have 84% statistical power to detect an odds ratio of 1.4 at a 5% statistical significance level (two-sided test) for a dominant allele with a prevalence of 20%.
The Val655Ile polymorphism was analyzed by using the previously described polymerase chain reaction–restriction fragment length polymorphism assay (1). The frequency of the valine allele (0.24 in case patients and 0.23 in control subjects) was similar to that reported previously for Caucasians and higher than among Chinese subjects. We observed neither a deviation from the expected Hardy–Weinberg distribution nor a statistically significant difference in the genotype distribution of the cancer group compared with the control group among this German Caucasian population (P = .83). This lack of association remained when the data were stratified into two groups by age, i.e., 45 years or younger and older than 45 years (Table 1
). We also did not find any difference when the cancer case patients were stratified according to histologic subtype, stage, grade, and hormone receptor status. However, when we examined the interaction between the HER2 polymorphism and other risk factors for breast cancer, we found statistically significant evidence for a differential effect by family history of breast cancer in a first-degree relative (P = .04 for interaction). Compared with wild-type Ile/Ile homozygotes, being a carrier of the valine allele was associated with a twofold increased risk for breast cancer only among women with a positive family history of breast cancer (Table 1). This statistical interaction was not reported in the Shanghai breast cancer study; however, that study would not have had adequate power due to the low rate of women with a family history of breast cancer (3.3%–3.7%) (1).
|
We conclude that the HER2 valine allele does not represent a breast cancer risk allele in a German Caucasian population but may be of relevance among patients with a history of breast cancer in first-degree relatives. Because of the unknown functional importance of the Val655Ile polymorphism, the observed association with familial breast cancer could also be caused by a linkage disequilibrium with functional allele(s) at other site(s). Therefore, these findings warrant further investigation in other sufficiently large studies.
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;92:412–7.
2
Ameyaw M, Thornton N, McLeod HL. Re: Population-based, case–control study of HER2 genetic polymorphism and breast cancer risk [letter]. J Natl Cancer Inst 2000;92:1947.
3
Baxter SW, Campbell IG. Re: Population-based, case–control study of HER2 genetic polymorphism and breast cancer risk [letter]. J Natl Cancer Inst 2001;93:557–9.
4 Chang-Claude J, Eby N, Kiechle M, Bastert G, Becher H. Breastfeeding and breast cancer risk by age 50 among women in Germany. Cancer Causes Control 2000;11:687–95.[CrossRef][Web of Science][Medline]cancerlit;20516818
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S Beauclair, P Formento, J. Fischel, W Lescaut, R Largillier, E Chamorey, P Hofman, J. Ferrero, G Pages, and G Milano Role of the HER2 [Ile655Val] genetic polymorphism in tumorogenesis and in the risk of trastuzumab-related cardiotoxicity Ann. Onc., August 1, 2007; 18(8): 1335 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Han, D. Kang, J. E. Lee, I. A. Park, J.-Y. Choi, K.-M. Lee, J. Y. Bae, S. Kim, E.-S. Shin, J. E. Lee, et al. A Haplotype Analysis of HER-2 Gene Polymorphisms: Association with Breast Cancer Risk, HER-2 Protein Expression in the Tumor, and Disease Recurrence in Korea Clin. Cancer Res., July 1, 2005; 11(13): 4775 - 4778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Frank, K. Hemminki, M. Wirtenberger, J. L. Bermejo, P. Bugert, R. Klaes, R. K. Schmutzler, B. Wappenschmidt, C. R. Bartram, and B. Burwinkel The rare ERBB2 variant Ile654Val is associated with an increased familial breast cancer risk Carcinogenesis, March 1, 2005; 26(3): 643 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Montgomery, D. M. Gertig, S. W. Baxter, R. L. Milne, G. S. Dite, M. R. E. McCredie, G. G. Giles, M. C. Southey, J. L. Hopper, and I. G. Campbell The HER2 I655V Polymorphism and Risk of Breast Cancer in Women < Age 40 Years Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1109 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hauptmann, A. J. Sigurdson, N. Chatterjee, J. L. Rutter, D. A. Hill, M. M. Doody, and J. P. Struewing Re: Population-Based, Case-Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk J Natl Cancer Inst, August 20, 2003; 95(16): 1251 - 1252. [Full Text] [PDF]
|
|
|
|
|
|
A. Hishida, N. Hamajima, H. Iwata, K. Matsuo, K. Hirose, N. Emi, and K. Tajima Re: Population-Based, Case-Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk J Natl Cancer Inst, December 4, 2002; 94(23): 1807 - 1808. [Full Text] [PDF]
|
|
|
|
|
|
K. Y. K. Chan, A. N. Y. Cheung, S.-P. Yip, H.-H. Ko, T.-W. Lai, and U.-S. Khoo Re: Population-Based Case-Control Study of HER2 Genetic Polymorphism and Breast Cancer Risk J Natl Cancer Inst, October 16, 2002; 94(20): 1581 - 1582. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||