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Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma

Zubor, Pavola; Kajo, Karolb; Stanclova, Andreab; Szunyogh, Norberta; Galo, Silvestera; Dussan, Carlos A.a d; Minarik, Gabrielc; Visnovsky, Jozefa; Danko, Jana

European Journal of Cancer Prevention: February 2008 - Volume 17 - Issue 1 - p 33-38
doi: 10.1097/CEJ.0b013e3280145e4b
Research papers: Breast Cancer

Studies on the association between the Ile to Val polymorphism at codon 655 of the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to breast cancer have been reported for almost all ethnic populations, with both positive or negative conclusions. No study, however, has yet been focused on the possible association between this gene and its predisposition to benign breast lesions, especially on risk for fibroadenoma. We aimed to study the association of the single nucleotide polymorphism V655 HER-2 gene polymorphism with histologically verified breast fibroadenoma risk. We conducted a molecular epidemiological case–control study of 70 breast fibroadenoma cases without cellular atypia and 172 healthy female controls. We found that the Val variant allele and genotype frequency of this polymorphism is higher in cases with fibroadenoma; however, this difference was not significant (allele Val 655: 27.86 and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71 and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls, respectively). Applying logistic regression analysis, we found an increased risk of fibroadenoma formation in carriers of the Val allele (odds ratio=1.17; 95% confidence interval=0.67–2.05), in which the highest risk was associated with homozygous genotype (odds ratio=3.07; 95% confidence interval=0.97–9.72), but this risk was not significant. Stratification by age (cut-off 45 years) revealed the highest risk of fibroadenoma among young women homozygous for the Val allele (odds ratio=3.30). The risk, however, was slightly increased (odds ratio=1.24) among older carriers of the aberrant allele in their genotype as well, but it was not significant. In spite of insignificant differences, our results indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation. The significance of this susceptibility, however, will have to be verified by larger studies.

Departments of aObstetrics and Gynecology

bPathological Anatomy, Jessenius Faculty of Medicine, Martin

cDepartment of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic

dDepartment of Senology, European Institute of Oncology, Milan, Italy

Correspondence to Pavol Zubor, MD, PhD, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, Kollarova 2, 03659 Martin, Slovak Republic

Tel: +421 434 203 242; fax: +421 434 134 185; e-mail:

Received 21 April 2006 Accepted 15 September 2006

© 2008 Lippincott Williams & Wilkins, Inc.