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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

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dc.contributor.authorHan, Wonshik-
dc.contributor.authorKang, Daehee-
dc.contributor.authorLee, Jong Eun-
dc.contributor.authorPark, In Ae-
dc.contributor.authorChoi, Ji-Yeob-
dc.contributor.authorLee, Kyung-Mu-
dc.contributor.authorBae, Ji Yeon-
dc.contributor.authorKim, Sook-
dc.contributor.authorShin, Eun-Soon-
dc.contributor.authorLee, Jeong Eon-
dc.contributor.authorShin, Hyuk-Jae-
dc.contributor.authorKim, Seok Won-
dc.contributor.authorKim, Sung-Won-
dc.contributor.authorNoh, Dong-Young-
dc.date.accessioned2009-11-09T06:20:46Z-
dc.date.available2009-11-09T06:20:46Z-
dc.date.issued2005-07-08-
dc.identifier.citationClin Cancer Res. 2005 Jul 1;11(13):4775-8en
dc.identifier.issn1078-0432 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16000574-
dc.identifier.urihttps://hdl.handle.net/10371/11584-
dc.description.abstractPURPOSE: 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.en
dc.language.isoen-
dc.publisherAmerican Association for Cancer Researchen
dc.subjectAdulten
dc.subjectAllelesen
dc.subjectBreast Neoplasms/genetics/metabolism/*pathologyen
dc.subjectCase-Control Studiesen
dc.subjectDisease-Free Survivalen
dc.subjectFemaleen
dc.subjectGene Frequencyen
dc.subjectGenotypeen
dc.subjectHaplotypes/*geneticsen
dc.subjectHumansen
dc.subjectImmunohistochemistryen
dc.subjectKoreaen
dc.subjectLinkage Disequilibriumen
dc.subjectLymphatic Metastasisen
dc.subjectMiddle Ageden
dc.subjectNeoplasm Recurrence, Localen
dc.subjectNeoplasm Stagingen
dc.subjectPrognosisen
dc.subjectReceptor, erbB-2/*genetics/metabolismen
dc.subjectRisk Factorsen
dc.subjectPolymorphism, Single Nucleotide-
dc.titleA haplotype analysis of HER-2 gene polymorphisms: association with breast cancer risk, HER-2 protein expression in the tumor, and disease recurrence in Koreaen
dc.typeArticleen
dc.contributor.AlternativeAuthor한원식-
dc.contributor.AlternativeAuthor강대희-
dc.contributor.AlternativeAuthor이종은-
dc.contributor.AlternativeAuthor박인애-
dc.contributor.AlternativeAuthor최지엽-
dc.contributor.AlternativeAuthor이경무-
dc.contributor.AlternativeAuthor배지연-
dc.contributor.AlternativeAuthor김숙-
dc.contributor.AlternativeAuthor신은순-
dc.contributor.AlternativeAuthor이정언-
dc.contributor.AlternativeAuthor신혁재-
dc.contributor.AlternativeAuthor김석원-
dc.contributor.AlternativeAuthor김성원-
dc.contributor.AlternativeAuthor노동영-
dc.identifier.doi10.1158/1078-0432.CCR-04-2208-
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