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Jeffrey Smith
Faculty Member
Last active: 3/14/2018

Heritable variation of ERBB2 and breast cancer risk.

Breyer JP, Sanders ME, Airey DC, Cai Q, Yaspan BL, Schuyler PA, Dai Q, Boulos F, Olivares MG, Bradley KM, Gao YT, Page DL, Dupont WD, Zheng W, Smith JR
Cancer Epidemiol Biomarkers Prev. 2009 18 (4): 1252-8

PMID: 19336545 · PMCID: PMC2730036 · DOI:10.1158/1055-9965.EPI-08-1202

Amplification of the epithelial growth factor receptor gene ERBB2 (HER2, NEU) in breast cancer is associated with a poor clinical prognosis. In mammary gland development, this receptor plays a role in ductal and lobuloalveolar differentiation. We conducted a systematic investigation of the role of genetic variation of the ERBB2 gene in breast cancer risk in a study of 842 histologically confirmed invasive breast cancer cases and 1,108 controls from the Shanghai Breast Cancer Study. We observed that the ERBB2 gene resides within a locus of high linkage disequilibrium, composed of three major ancestral haplotypes in the study population. These haplotypes are marked by simple tandem repeat and single nucleotide polymorphisms, including the missense variants I655V and P1170A. We observed a risk-modifying effect of a highly polymorphic simple tandem repeat within an evolutionarily conserved region, 4.4 kb upstream from the ERBB2 transcription start site. Under a dominant genetic model, the age-adjusted odds ratio was 1.74 (95% confidence interval, 1.27-2.37). Its association with breast cancer, and with breast cancer stratified by histology, by histologic grade, and by stage, remained significant after correction for multiple comparisons. In contrast, we observed no association of ERBB2 single nucleotide polymorphism haplotypes with breast cancer predisposition.

MeSH Terms (19)

Adenocarcinoma Adult Breast Neoplasms Carcinoma, Ductal, Breast Carcinoma, Lobular Case-Control Studies China Female Genetic Predisposition to Disease Haplotypes Humans Linkage Disequilibrium Middle Aged Mutation, Missense Polymorphism, Single Nucleotide Prognosis Receptor, ErbB-2 Risk Factors Tandem Repeat Sequences

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