Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa

Abstract

AbstractBackgroundElucidation of specific and recurrent/founder pathogenic variants (PVs) inBRCA(BRCA1andBRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations.MethodsTo establish the knowledge aboutBRCAPVs and to determine the prevalence of the specific and recurrent/founder variants inBRCAgenes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia.ResultsSearch of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated bothBRCA1andBRCA2genes, four studies examined the entire coding region of theBRCA1gene, and six studies in which the analysis was limited to a fewBRCA1and/orBRCA2exons. Overall, 76 PVs (44 inBRCA1and32 inBRCA2) were identified in 196 BC and/or OC patients (129BRCA1and 67BRCA2carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) inBRCA1and 8/32 (25%) inBRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, theBRCA1c.68_69del andBRCA1c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex:BRCA1c.181T>G,BRCA1c1016dupA). The most well characterized PVs are four inBRCA1gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one inBRCA2[c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total establishedBRCA1PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of allBRCA1North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants includingBRCA13279delC,BRCA1c.5266dup andBRCA2c.1310_1313detAAGA was detected in 42 patients.BRCA1founder variants explain around 36.4% (47/129) of BC and outnumberBRCA2founder variants by a ratio of ≈3:1.ConclusionsTesting BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.