376 - Genetic polymorphism in aurora-a as a risk factor in Egyptian women with breast cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Breast Cancer
Translational Research
Presenter Magdy Saber
Authors M.M. Saber1, S.Y. Akel2, G.T. Ali3, N.H. Ibrahim2
  • 1Dept. Medical Oncology, National Cancer Institute, 12511 - Cairo/EG
  • 2Clinical Pathology Department, National Cancer Institute, 1215 - Cairo/EG
  • 3Clinical Pathology Deaprtment, National Cancer Institute, 1215 - Cairo/EG

Abstract

Introduction

Although many risk factors have been identified, the cause of any individual breast cancer (BC) is most often unknowable. Aurora A, the gene, encoding serine/threonine kinase, has been shown to be over expressed in many tumors, noticeably in BC. The aim is to study the single nucleotide polymorphism in Aurora-A, and compare the frequency distributions of different genotypes between patients with BC and those with fibroadenoma to define its tumorigenic contribution to BC development.

Patients and methods

This study was conducted on 60 pathologically confirmed BC patients, 20 patients with fibroadenoma and 40 frequency matched controls. There were no age, stage or histology restrictions.Serum CA-15-3&estradiol were measured. DNA was isolated from peripheral blood lymphocytes for genotyping of Aurora A at the T91A (Phe31Ile) site and were analyzed by PCR–RFLP assay.

Results

This study showed that women carrying the Ile/Ile genotype had an increased risk of developing BC (P = 0.04). Logistic regression analysis showed that subjects having IIe/IIe genotype had a 9.3fold increased risk of developing BC compared with those with the Phe/Phe genotype (OR 9.3;95% CI 1.12-77.69). The heterozygous Phe/IIe genotype was not significantly associated with the risk of cancer, suggesting a possible recessive effect of the polymorphism. No significant association was observed between the polymorphism and the risk of fibroadenoma. Patients with negative ER &PR were more likely to carry the IIe/IIe genotype compared with positive ER &PR positive patients (34.8% vs 5.4%). Serum estradiol showed significant increase in the BC category (p= 0.016), while, no significant difference was observed between the benign and the control categories (p = 0.41). The presence of +ve family history (FH) of BC and history of sex hormone intake showed significant increase in BC category when compared to control group and benign group. In BC group, patients with +ve FH had 7.5 times the chance of carrying IIe/IIe genotype compared to patients with –ve FH (OR7.5; 95% CI 1.53-36.71, P0.01).

Conclusion

This study provides the evidence that the Aurora-A Ile/Ile genotype is associated with an increased risk for the occurrence but not progression of BC.

Disclosure

All authors have declared no conflicts of interest.