High prevalence of two BRCA1 mutations, 4154delA and 5382insC, in Latvia

Abstract

Our aim was to characterise the germline BRCA1 mutation profile in Latvian breast cancer and ovarian cancer patients, to develop an effective BRCA1 gene mutation detection strategy, and to document genotype-phenotype correlations in mutation carriers. The entire BRCA1 gene was analysed in 75 breast cancer and 30 ovarian cancer patients. Screening for three mutations (5382insC, 4154delA and 300T>G) was carried out in 55 breast cancer and 66 ovarian cancer patients, and for two mutations, 5382insC and 4154delA, in 376 unselected patients with any cancer (including 51 breast cancer and 29 ovarian cancers) and 215 women with any gynaecological tumour. Mutation detection techniques used were SSCP/HD analysis or F-SSCP (ABI PRISM 310). Five different deleterious mutations were detected by analysis of the entire BRCA1 gene. The proportion of cases with mutations amongst 50 breast cancer patients diagnosed before 48 years was 26.0% (95% CI: 14.6-40.3%). Two mutations (5382insC and 4154delA) made up more than 80% of all mutations identified by the analysis of the entire BRCA1 gene in Latvia, at present. Further screening for only the prevalent mutations in different cancer patient groups resulted in the identification of 53 more mutation carriers. We conclude that breast cancer diagnosed before the age of 48 years and ovarian cancer before 65 years are criteria for DNA testing to be offered to women in Latvia, regardless of cancer history in the family. The observed associations of specific prevalent mutations with cancer site and age at onset of disease are discussed.

Epidemiological, Clinical, Molecular Features and Early Detection Strategy of Most Frequent Hereditary Cancers in Latvia

“…No mutation was detected in 300T/G. These results are the observations published by Tikhomirova et al (2005) and Gronwald et al (2008).…”

“…In the breast cancer group the most common mutations were detected in ex20 (5382 insC) -48 and only 16 mutations ex11,17 (4153delA). The high occurrence of mutation ex20 (5382 insC) is described also in other East European populations (Gorski et al, 2000;Tikhomirova et al, 2005). Similar results were found in the patient group with ovarian cancer.…”

“…We consider our results as not conclusive as well concerning the role of the Trp149Stop variant in cancer susceptibility. This mutation was considered not to be associated with sporadic cancer (Tikhomirova et al, 2005). Taking into account the rather high prevalence of the 149Stop allele among cancer patients (more than 4%) in our study, we suggest that cancer risk associated with it should be examined more carefully in sporadic and familial cancer cases.…”

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] .…”