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

Autor: Sonia Abdelhak, Hamouda Boussen, Olfa Messaoud, Mohamed Samir Boubaker, Majdi Nagara, Mariem Ben Rekaya, Amel Benammar Elgaaied, Lotfi Chouchane, Shan Jingxuan, Lilia Romdhane, Yosr Hamdi, Ridha Mrad
Přispěvatelé: Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Weill Cornell Medicine [Qatar], Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM), Hôpital Charles Nicolle [Tunis], Hôpital Abderrahmen Mami, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, This work was supported by the 'Qatar National Research Foundation' (NPRP 08–083–3-031) that contributed to the design of the study, collection, analysis, interpretation of data and in writing the manuscript., The authors would like to thank all the individuals who took part in this study and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out.
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Cancer Research
Linkage disequilibrium
Population genetics
Linkage Disequilibrium
0302 clinical medicine
Gene Frequency
Haplotype analysis
MESH: Healthy Volunteers
International HapMap Project
MESH: Genetic Loci/genetics
Genetics
MESH: Middle Aged
MESH: Polymorphism
Single Nucleotide
Middle Aged
MESH: Genome-Wide Association Study
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Healthy Volunteers
MESH: Breast Neoplasms/genetics
3. Good health
SNP genotyping
Oncology
030220 oncology & carcinogenesis
MESH: African Continental Ancestry Group/genetics
Female
MESH: Tunisia
MESH: Haplotypes/genetics
Research Article
Adult
Tunisia
Black People
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
lcsh:RC254-282
Polymorphism
Single Nucleotide
03 medical and health sciences
Breast cancer
MESH: Computer Simulation
MESH: Genetic Predisposition to Disease
medicine
Humans
Computer Simulation
Genetic Predisposition to Disease
MESH: Linkage Disequilibrium/genetics
Allele frequency
Genetic association
Breast cancer susceptibility
MESH: Humans
Functional analysis
Haplotype
MESH: Adult
medicine.disease
MESH: Male
030104 developmental biology
Haplotypes
Genetic Loci
Expression quantitative trait loci
MESH: Gene Frequency/genetics
MESH: Female
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Genome-Wide Association Study
Zdroj: BMC Cancer
BMC Cancer, BioMed Central, 2018, 18 (1), pp.1295. ⟨10.1186/s12885-018-5133-8⟩
BMC Cancer, Vol 18, Iss 1, Pp 1-14 (2018)
ISSN: 1471-2407
DOI: 10.1186/s12885-018-5133-8
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12885-018-5133-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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