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. 2020 May 5;12(5):1158.
doi: 10.3390/cancers12051158.

Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)-Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes

Lorena Incorvaia  1 , Daniele Fanale  2 , Giuseppe Badalamenti  2 , Marco Bono  2 , Valentina Calò  2 , Daniela Cancelliere  2 , Marta Castiglia  2 , Alessia Fiorino  2 , Alessia Pivetti  2 , Nadia Barraco  2 , Sofia Cutaia  2 , Antonio Russo  2 , Viviana Bazan  2
Affiliations

Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)-Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes

Lorena Incorvaia et al. Cancers (Basel). .

Abstract

Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlinico "P. Giaccone" of Palermo from January 1999 to October 2019. Thirty PVs were more frequently observed in the Sicilian population but only some of these showed a specific territorial prevalence, unlike other Italian and European regions. This difference could be attributed to the genetic heterogeneity of the Sicilian people and its historical background. Therefore hereditary breast and ovarian cancers could be predominantly due to BRCA1/2 PVs different from those usually detected in other geographical areas of Italy and Europe. Our investigation led us to hypothesize that a higher prevalence of some germline BRCA PVs in Sicily could be a population-specific genetic feature of BRCA-positive carriers.

Keywords: BRCA1; BRCA2; Sicilian population; breast cancer; founder variants; genetic testing; germline pathogenic variants; hereditary breast and ovarian cancer; ovarian cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Breast and/or ovarian cancer patients harboring germline BRCA1/2 pathogenic variants (PVs). 200 (14.8%) out of 1346 probands with breast and/or ovarian cancer had germline PVs in BRCA1/2 genes. (a) 102 (51%) were BRCA1 PV carriers, (b) 96 (48%) were BRCA2 PV carriers and 2 patients (1%) showed a double heterozygosity for BRCA1 and BRCA2 PVs.
Figure 2
Figure 2
Type of tumors in all individuals carrier of germline BRCA1 (a) or BRCA2 (b) PVs (probands and family members).
Figure 3
Figure 3
Geographical distribution of the hereditary breast/ovarian cancer families in Sicily.
See this image and copyright information in PMC

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