Clinical Significance of Epigenetic Inactivation of hMLH1 and BRCA1 in Tunisian Patients with Invasive Breast Carcinoma

Sondes Karray-Chouayekh,Tahia Sellami-Boudawara,Ali Gargouri,Fatma Trifa,Nouredine Boujelbane,Raja Mokdad-Gargouri,Mounir Frikha,Jamel Daoud,Abdelmajid Khabir

doi:10.1155/2009/369129

Sondes Karray-Chouayekh, Tahia Sellami-Boudawara + Show 7 more

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https://doi.org/10.1155/2009/369129

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Abstract

Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) and BRCA1 (breast cancer 1, early onset) in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P = .015) and 5-years disease free survival (P = .016) while hMLH1 methylation was more frequent in larger tumors (P = .002) and in presence of distant metastasis (P = .004). Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P = .006) and with overall survival (P = .015) suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.

Highlights

Breast cancer is the first cause of cancer mortality among women worldwide and the overall lifetime risk for developing invasive breast cancer is estimated to 10% [1]
It has been demonstrated that CpG islands hypermethylation is implicated in the loss of expression of critical tumor suppressor and growth regulatory genes leading to cancer development and progression [5,6,7,8]
By multivariate analysis, we found a significant association of BRCA1 promoter methylation with clinical stage, tumor size and 5-year survival (P = .022, .037 and .017, resp., Table 3)

Summary

Introduction

Breast cancer is the first cause of cancer mortality among women worldwide and the overall lifetime risk for developing invasive breast cancer is estimated to 10% [1]. In Tunisia, breast cancer is the second most frequent cancer among females and in the south area the incidence is of 30/100000 [2]. Tunisian breast cancer is characterized by a particular aggressive profile compared with Western countries as the incidence is more prevalent in young (

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