Characterization of familial breast cancer in Saudi Arabia.

Adnan Merdad,Adeel G Chaudhary,Fatma Al-Thubaiti,Taha Koumosani,Jaudah Al-Maghrabi,Ibtessam R Hussein,Nehad Shaer,Adel M Abuzenadah,Mamdooh A Gari,Ashraf Dallol,Hana Tashkandi,Mohammed H Al-Qahtani,Shireen Hussein,Shadi Al-Khayat

doi:10.1186/1471-2164-16-s1-s3

Abstract

BackgroundThe contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform.ResultsWe have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway.ConclusionThe disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

Highlights

The contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset
We have identified one novel frameshift mutation affecting BRCA2 caused by an -/AC insertion affecting one patient only (Table 2)
Other BRCA1 or BRCA2 variants identified were previously reported in dbSNP137

Summary

Introduction

The contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. GWAS studies led to the identification of 21 susceptibility loci that are considered only as low risk alleles [9,12,13,14,15,16,17] All these factors combined can account for only 35% of heritable breast cancer with the majority of cases remain with an unknown genetic etiology [18]. A remarkable characteristic of breast cancer in this population is the relatively younger age of onset of the disease where the majority of cases (sporadic or familial) are diagnosed with invasive ductal carcinoma before they are 50 years old [19] This early onset could be attributed, at least partly, to undetermined genetic susceptibility factors accumulating in the population due to consanguineous marriages and increased exposure to environmental insults due to life-style shifts in the past two decades

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Discussion

Conclusion