Germline mutational spectrum in Armenian breast cancer patients suspected of hereditary breast and ovarian cancer.

Hereditary breast and ovarian cancer (HBOC) can be identified by genetic testing of cancer-causing genes. In this study, we identified a spectrum of genetic variations among 76 individuals of Armenian descent either with a family history of cancer or breast cancer before the age of 40. We screened 76 suspected HBOC patients and family members as well as four healthy controls using a targeted and hereditary comprehensive cancer panel (127 genes). We found 26 pathogenic (path) and 6 likely pathogenic (LPath)variants in 6 genes in 44 patients (58%); these variants were found in BRCA1 (17), BRCA2 (19), CHEK2 (4), PALB2 (2), and NBN (1). A few different variants were found in unrelated individuals; most notably, variant p.Trp1815Ter in the BRCA1 gene occurred in four unrelated patients. We did not find any known significant variants in five patients. Comprehensive cancer panel testing revealed pathogenic variants in cancer genes other than BRCA1 and BRCA2, suggesting that testing only BRCA1 and BRCA2 would have missed 8 out of 44 suspected HBOC patients (18%). These data also confirm that a comprehensive cancer panel testing approach could be an appropriate way to identify most of the variants associated with hereditary breast cancer.

Prevention of amyloidosis in familial Mediterranean fever with colchicine: a case-control study in Armenia.

OBJECTIVE: To determine whether or not the use of colchicine decreases the risk of amyloidosis among Armenian patients with familial Mediterranean fever (FMF). SUBJECTS AND METHODS: The study included 99 Armenian patients from the Center of Medical Genetics database with genetically ascertained FMF; 33 had renal amyloidosis and 66 were randomly selected control patients without renal amyloidosis. Self- reported colchicine use was assessed by interviewer-based questionnaire. RESULTS: The patients with incident amyloidosis were more likely to be older men, but younger at the time of disease onset, and more likely to have had a family history of amyloidosis and M694F mutation in the MEFV gene compared to patients without amyloidosis. The risk of amyloidosis decreased with adequate colchicine use rather than nonadequate use (adjusted odds ratio, OR, 0.48, 95% confidence interval, CI, 0.16-1.43), continuous colchicine use rather than interrupted use (adjusted OR 0.15, 95% CI 0.04-0.53), earlier rather than later initiation age of colchicine treatment (adjusted OR 0.95, 95% CI 0.90-1.01), current colchicine rather than ever/never colchicine use (adjusted OR 0.20, 95% CI 0.05-0.89). CONCLUSION: The study demonstrated that colchicine treatment is effective in preventing amyloidosis among Armenian patients with FMF and that earlier initiation and continuous therapy at an adequate dose of 1.2-1.8 mg/day may be associated with a decreased amyloidosis risk among Armenian patients with FMF.