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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. 2005 Jul 01; 11(13):4775-8.CC

Abstract

PURPOSE

A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been extensively studied with inconclusive results. The purpose of this study was to investigate the association between common variants of HER-2 and breast cancer risk, HER-2 expression, and survival using a haplotype-based stepwise approach.

EXPERIMENTAL DESIGN

Twenty-nine SNPs listed in the National Center for Biotechnology Information database were screened to identify novel polymorphisms of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Using these six SNPs, linkage disequilibrium and haplotype patterns were characterized. We tested association between the haplotypes and breast cancer in a large case-control study (n=1,039 cases and 995 controls). Six-hundred two breast cancer patients with follow-up at least 24 months were analyzed for outcome in relation to haplotype. Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer.

RESULTS

All six SNPs showed a strong linkage disequilibrium pattern and were considered to belong to one haplotype block. Two haplotype-tagging SNPs (I655V and P1170A) for three common haplotypes (>5%) were genotyped in cases and controls. The haplotypes and individual SNPs were not associated with breast cancer risk. In patients with at least one copy of haplotype I (the most common haplotype), HER-2 expression was 1.5 times higher (P = 0.009) and the prognosis was worse (P = 0.032) compared with patients without having that haplotype.

CONCLUSIONS

Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome.

Authors+Show Affiliations

Department of Surgery, Seoul National University College of Medicine, and DNA Link Inc., Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16000574

Citation

Han, Wonshik, 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." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 13, 2005, pp. 4775-8.
Han W, Kang D, Lee JE, 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. 2005;11(13):4775-8.
Han, W., Kang, D., Lee, J. E., Park, I. A., Choi, J. Y., Lee, K. M., Bae, J. Y., Kim, S., Shin, E. S., Lee, J. E., Shin, H. J., Kim, S. W., Kim, S. W., & Noh, D. Y. (2005). 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. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(13), 4775-8.
Han W, 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. 2005 Jul 1;11(13):4775-8. PubMed PMID: 16000574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Han,Wonshik, AU - Kang,Daehee, AU - Lee,Jong Eun, AU - Park,In Ae, AU - Choi,Ji-Yeob, AU - Lee,Kyung-Mu, AU - Bae,Ji Yeon, AU - Kim,Sook, AU - Shin,Eun-Soon, AU - Lee,Jeong Eon, AU - Shin,Hyuk-Jae, AU - Kim,Seok Won, AU - Kim,Sung-Won, AU - Noh,Dong-Young, PY - 2005/7/8/pubmed PY - 2005/12/13/medline PY - 2005/7/8/entrez SP - 4775 EP - 8 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 13 N2 - PURPOSE: A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been extensively studied with inconclusive results. The purpose of this study was to investigate the association between common variants of HER-2 and breast cancer risk, HER-2 expression, and survival using a haplotype-based stepwise approach. EXPERIMENTAL DESIGN: Twenty-nine SNPs listed in the National Center for Biotechnology Information database were screened to identify novel polymorphisms of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Using these six SNPs, linkage disequilibrium and haplotype patterns were characterized. We tested association between the haplotypes and breast cancer in a large case-control study (n=1,039 cases and 995 controls). Six-hundred two breast cancer patients with follow-up at least 24 months were analyzed for outcome in relation to haplotype. Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer. RESULTS: All six SNPs showed a strong linkage disequilibrium pattern and were considered to belong to one haplotype block. Two haplotype-tagging SNPs (I655V and P1170A) for three common haplotypes (>5%) were genotyped in cases and controls. The haplotypes and individual SNPs were not associated with breast cancer risk. In patients with at least one copy of haplotype I (the most common haplotype), HER-2 expression was 1.5 times higher (P = 0.009) and the prognosis was worse (P = 0.032) compared with patients without having that haplotype. CONCLUSIONS: Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16000574/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_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16000574 DB - PRIME DP - Unbound Medicine ER -