Geographical distribution of Slovenian BRCA1/2 families according to family origin: implications for genetic screening

• Published in: Clinical genetics Vol. 85; no. 1; pp. 59 - 63
• Main Authors: Krajc, M, Zadnik, V, Novaković, S, Stegel, V, Teugels, E, Bešič, N, Hočevar, M, Vakselj, A, De Grève, J, Žgajnar, J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2014
• Subjects: BRCA1; BRCA1 protein; BRCA2; Cancer; Family; Female; Genes, BRCA1; Genes, BRCA2; Genetic counseling; Genetic Testing; geographical distribution; Hereditary Breast and Ovarian Cancer Syndrome - diagnosis; Hereditary Breast and Ovarian Cancer Syndrome - epidemiology; Hereditary Breast and Ovarian Cancer Syndrome - genetics; Humans; Male; Mutation; Phylogeography; recurrent mutations; Slovenia; Slovenia - epidemiology; Slovenia; recurrent mutations; BRCA1; Slovenia; BRCA2; genetic testing; geographical distribution
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12119

Knowledge of the geographical distribution of highly recurrent mutations may be useful for efficient screening in cancer families. Since the cloning of the BRCA1/2 genes, it is known that the wide spectrum of deleterious mutations shows high ethnic and geographic heterogeneity. In this study, we have tested probands from 582 breast/ovarian cancer families and positioned all 156 BRCA1/2 families on the map according to the family origin. We observed that high‐risk families with the same recurrent mutation present a typical geographical distribution and that different recurrent mutations may show different distribution patterns. We then evaluated the genetic screening implications of this heterogeneous prevalence of the most recurrent mutations found [300T>G(c.181T>G), 1806C>T(c.1687C>T), 969ins7(c.844_850dupTCATTAC), 5382insC(c.5266dupC), 235G>A(c.116G>A) in BRCA1 and IVS16‐2A>G(c.7806‐2A>G) in BRCA2]. On the basis of these results, specific testing procedures for new incident cases may be offered according to their family origins and, according to the information regarding clusters revealed in this study, the individuals (especially those at low risk), originating from regions with clusters, might be screened preferentially for cluster mutations and analysis may be simplified according to the family origin.