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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

A genome wide SNP genotyping study in the Tunisian population: specific reporting on a subset of common breast cancer risk loci

Authors: Yosr Hamdi, Mariem Ben Rekaya, Shan Jingxuan, Majdi Nagara, Olfa Messaoud, Amel Benammar Elgaaied, Ridha Mrad, Lotfi Chouchane, Mohamed Samir Boubaker, Sonia Abdelhak, Hamouda Boussen, Lilia Romdhane

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Breast cancer is the most common cancer in women worldwide. Around 50% of breast cancer familial risk has been so far explained by known susceptibility alleles with variable levels of risk and prevalence. The vast majority of these breast cancer associated variations reported to date are from populations of European ancestry. In spite of its heterogeneity and genetic wealth, North-African populations have not been studied by the HapMap and the 1000Genomes projects. Thus, very little is known about the genetic architecture of these populations.

Methods

This study aimed to investigate a subset of common breast cancer loci in the general Tunisian population and to compare their genetic composition to those of other ethnic groups. We undertook a genome-wide haplotype study by genotyping 135 Tunisian subjects using the Affymetrix 6.0-Array. We compared Tunisian allele frequencies and linkage disequilibrium patterns to those of HapMap populations and we performed a comprehensive assessment of the functional effects of several selected variants.

Results

Haplotype analyses showed that at risk haplotypes on 2p24, 4q21, 6q25, 9q31, 10q26, 11p15, 11q13 and 14q32 loci are considerably frequent in the Tunisian population (> 20%). Allele frequency comparison showed that the frequency of rs13329835 is significantly different between Tunisian and all other HapMap populations. LD-blocks and Principle Component Analysis revealed that the genetic characteristics of breast cancer variants in the Tunisian, and so probably the North-African populations, are more similar to those of Europeans than Africans.
Using eQTl analysis, we characterized rs9911630 as the most strongly expression-associated SNP that seems to affect the expression levels of BRCA1 and two long non coding RNAs (NBR2 and LINC008854). Additional in-silico analysis also suggested a potential functional significance of this variant.

Conclusions

We illustrated the utility of combining haplotype analysis in diverse ethnic groups with functional analysis to explore breast cancer genetic architecture in Tunisia. Results presented in this study provide the first report on a large number of common breast cancer genetic polymorphisms in the Tunisian population which may establish a baseline database to guide future association studies in North Africa.
Appendix
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Metadata
Title
A genome wide SNP genotyping study in the Tunisian population: specific reporting on a subset of common breast cancer risk loci
Authors
Yosr Hamdi
Mariem Ben Rekaya
Shan Jingxuan
Majdi Nagara
Olfa Messaoud
Amel Benammar Elgaaied
Ridha Mrad
Lotfi Chouchane
Mohamed Samir Boubaker
Sonia Abdelhak
Hamouda Boussen
Lilia Romdhane
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5133-8

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