Prevalence of the most frequent BRCA1 mutations in Polish population

Abstract

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

“…Miki et al describes that BRCA1 is a strong candidate for the breast and ovary cancer (Miki et al, 1994). The spectrum of BRCA1 mutations has been characterized in different populations worldwide, with significant variation of the relative contribution of these genes to hereditary cancer between populations (Brozek et al, 2011). However, the contribution of mutations in these two genes to breast cancer patients in the Indian population remains relatively unexplored apart from a few small studies (Saxena et al, 2006).…”

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.…”

“…In families with an available family history and at least 1 case of pdac or otherwise at risk of pdac (n = 211), tumours in 152 patients (72.0%) were classified as sporadic because the family had no history of pdac and did not meet criteria for a genetic syndrome associated with hereditary pdac. Another 59 patients (28.0%) had an increased likelihood of hereditary pdac either because of multiple pdac diagnoses in the family [that is, familial pdac (fpdac), 18.5%], because of diagnosis of a genetic syndrome whose tumour spectrum includes pdac (3.8%), or because of young age of onset (diagnosed with pdac at 50 years of age or younger, 5.7%). Those observations are consistent with the distribution of pancpro scores for all pdac probands with an available pedigree (n = 175, Figure 1).…”

“…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] .…”

Imaging surveillance programs for women at high breast cancer risk in Europe: Are women from ethnic minority groups adequately included? (Review)

“…The Center from Szczecin (#17) (96)(97)(98) provided the majority of 212 women at high breast cancer risk with mammography and in a few cases with MRI, and reported 18 months of follow-up. All 379 women included in the krakow Center (#18) (99) received MRI, after undergoing mammography and ultrasound that had shown no abnormalities.…”