Author/Editor		Strojnik, Ksenija; Krajc, Mateja; Šetrajčič Dragoš, Vita; Stegel, Vida; Novaković, Srdjan; Blatnik, Ana
Title		Genetic testing results in Slovenian male breast cancer cohort indicate the BRCA2 7806-2A > G founder variant could be associated with higher male breast cancer risk
Type		članek
Vol. and No.		, št. Vol. 188
Publication year		2021
Volume		str. 811‐820
ISSN		0167-6806 - Breast cancer research and treatment
Language		eng
Abstract		To analyze the prevalence of pathogenic/likely pathogenic variants (P/LPVs) in BRCA1 and BRCA2 genes in the largest cohort of Slovenian male breast cancer (MBC) patients to date and to explore a possible correlation between the Slovenian founder variant BRCA2:c.7806-2A>G and predisposition to MBC. Methods We performed a retrospective analysis of 81 MBC cases who underwent genetic counseling and/or testing between January 1999 and May 2020. To explore a possible genotype%phenotype correlation, we performed additional analyses of 203 unrelated families with P/LPVs in BRCA2 and 177 cases of female breast cancer (FBC) in carriers of P/LPVs in BRCA2. Results Detection rate of P/LPVs in the BRCA1 and BRCA2 genes was 24.7% (20/81) with 95% of them in BRCA2 gene. The only two recurrent P/LPVs were BRCA2:c.7806-2A>G and BRCA2:c.3975_3978dupTGCT (9 and 5 MBC cases, respectively). In families with BRCA2:c.7806-2A>G, the incidence of MBC cases was higher compared to families with other P/ LPVs in BRCA2; however, the diference did not reach statistical signifcance (17.8% vs. 8.9%, p=0.105). BRCA2:c.7806- 2A>G was detected in both families with multiple cases of MBC. This splice-site variant represented a signifcantly higher proportion of all BRCA2 P/LPVs detected in MBC carriers compared to FBC carriers (47.4% vs. 26%, p=0.049). Conclusion We observed a high mutation detection rate and conclude this may be due to the prevalent BRCA2:c.7806-2A>G variant in Slovenia. Our results indicate a possible association between this variant and higher risk of breast cancer in males compared to other identifed P/LPVs in BRCA2.
Keywords		rak dojke moški rak dojke družinski rak BRCA breast cancer male breast cancer BRCA hereditary breast cancer