Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases

Abstract

BACKGROUND: In most Western populations, 5 -10% of all breast cancer cases can be attributed to major genetic factors such as predisposing mutations in BRCA1 and BRCA2, with early-onset cases generally considered as an indicator of genetic susceptibility. Specific BRCA1 and BRCA2 mutations or different mutation frequencies have been identified in specific populations and ethnic groups. Previous studies in Greek breast and/or ovarian cancer patients with family history have shown that four specific BRCA1 mutations, c.5266dupC, G1738R, and two large genomic rearrangements involving deletions of exons 20 and 24, have a prominent function in the population's BRCA1 and BRCA2 mutation spectrum. METHODS: To estimate the frequency of the above mutations in unselected Greek breast cancer women, we screened 987 unselected cases independently of their family history, collected from major Greek hospitals. RESULTS: Of the 987 patients, 26 (2.6%) were found to carry one of the above mutations in the BRCA1 gene: 13 carried the c.5266dupC mutation (1.3%), 6 carried the exon 24 deletion (0.6%), 3 carried the exon 20 deletion (0.3%), and 4 carried the G1738R mutation (0.4%). Among 140 patients with early-onset breast cancer (o40 years), 14 carried one of the four mutations (10.0%). CONCLUSION: These results suggest that a low-cost genetic screening for only the four prominent BRCA1 mutations may be advisable to all early-onset breast cancer patients of Greek origin.

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study

“…In our previous studies on the prevalence of BRCA1 and BRCA2 mutations in the Greek population (classified as Caucasian and genetically heterogeneous), we have found that a mutation in either gene is present in 20.5 % in a high-risk group selected for moderate to severe family history (n = 287) [31], while a BRCA1 founder mutation was present in 10 % of young (\40 years) breast cancer patients regardless of family history compared to 2.6 % of all breast cancer patients screened (n = 987) [32].…”

Detection of a novel mutation in exon 20 of the BRCA1 gene

“…Hereditary breast cancer constitutes 5-10% of all breast cancer cases. Major genetic factors, such as predisposing mutations in the BRCA1 and BRCA2 genes, are generally considered an indicator of genetic susceptibility in the case of early onset [4,5]. Women with a BRCA1 (MIM# 113705) or BRCA2 (MIM# 600185) germline mutation are at high risk of developing breast and/or ovarian cancer [6,7].…”

Establishing a Clinic-Based Pancreatic Cancer and Periampullary Tumour Research Registry in Quebec

“…Most subjects with pdac were white (79.2% maternal, 80.1% paternal), with an enrichment of cases (37.4%) having French-Canadian ancestry (at least 1 parental origin, Table iii). In addition, 56.8% of pdac-affected subjects had an ancestry (that is, French-Canadian, Ashkenazi Jewish, Greek, German, Polish, or Latvian) known to harbour recurrent germline ("founder") mutations in the BRCA1, BRCA2, and PALB2 pdac predisposing genes (Table iii) [11][12][13][14][15][16][17][18][19] . Table iii also shows data describing education, environmental exposures, weight loss, and history of type 2 diabetes and pancreatitis for enrolled patients with pdac.…”

“…Notably, more than half the enrolled patients in the qpcs affected with pdac (56.8%) had an ancestry (at least 1 parental origin) known to harbour founder BRCA1 and BRCA2 mutations [11][12][13][14][15][16][17][18][19] . The founder populations represent a genetically enriched subgroup ideal for gene discovery studies 8,[37][38][39] .…”