The CHEK2 1100delC allelic variant is not present in familial and sporadic breast cancer cases from Moroccan population.

Chaymaa Marouf,Omar Hajji,Hassan Jouhadi,Brehima Diakité,Sellama Nadifi,Abdellatif Benider,Amal Tazzite

doi:10.1186/s40064-014-0778-5

Abstract

PurposeThe cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage, whose defects has been associated with increased risk for breast cancer. The CHEK2 1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries. However, the 1100delC mutation has been investigated in different case-control studies and none in Moroccan population. The aim of this study was to evaluate the prevalence of this variant and determine its contribution to the development of breast cancer in sporadic cases and also in members of breast cancer families who tested negative or positive for a deleterious mutation in BRCA1/BRCA2.MethodsIn this case-control study we performed the CHEK2 1100delC mutation analysis by ASO-PCR in 134 breast cancer patients and 114 unaffected control individuals. Most of these families had several cases of breast cancer or ovarian cancer (or both).ResultsNo CHEK2 1100delC mutations were detected in any of 134 individuals, including 59 women diagnosed with breast cancer at an early age (<40 years), 10 women with bilateral breast cancer, and 6 women with ovarian cancer.ConclusionOur preliminary genetic analysis are consistent with the reported very low frequency of CHEK2 1100delC mutation in North American populations (compared with Northern Europe), rendering CHEK2 1100delC such as an unlikely to be major breast cancer susceptibility genes.

Highlights

Cell-cycle checkpoint kinase 2 (CHEK2 [MIM 604373]) is a tumor suppressor gene widely researched as a strong candidate gene for breast cancer susceptibility
High mutation rates are seen in Northern and Eastern European countries (Vahteristo et al 2002; CHEK2 Breast Cancer Case–control Consortium CHEK2*1100delC and susceptibility to breast cancer 2004; Meijers-Heijboer et al 2002) its frequency is much lower in North America (Mateus Pereira et al 2004; Offit et al 2003), whereas the mutation does not seem to be a triggering factor to breast cancer in Poland (Kwiatkowska et al 2006; Cybulski et al 2004) and some multiple-case breast cancer families from Australia (Jekimovs et al 2005)
134 breast cancer cases and 114 controls were successfully screened for the 1100delC variant of the CHEK2 gene using the ASO-PCR technique

Summary

Introduction

Cell-cycle checkpoint kinase 2 (CHEK2 [MIM 604373]) is a tumor suppressor gene widely researched as a strong candidate gene for breast cancer susceptibility The CHEK2 1100delC variant has been reported to be a low-penetrance breast cancer susceptibility allele (Vahteristo et al 2002; CHEK2 Breast Cancer Case–control Consortium CHEK2*1100delC and susceptibility to breast cancer 2004; Oldenburg et al 2003; Kuusisto Kirsi et al 2011) It results in an approximately two-fold risk of breast cancer in women and a ten-fold risk in men (van der Groep et al 2011). The frequency of CHEK2 1100delC seems to be very low in Southern Europe, Italy (Caligo et al 2004), Spain (Osorio et al 2004; Bellosillo et al 2005) and rare in Brazil (Zhang et al 2008)

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