BRCA1 gene-related hereditary susceptibility to breast and ovarian cancer in Latvia.

Purpose: In this report, we summarise data on BRCA1 gene analysis in Latvia to characterise criteria of genetic testing for breast and ovarian cancer susceptibility.

Material/methods: Analysis by SSCP/HD, MALDI-TOF mass spectrometry or DNA sequencing was used for mutation detection. Mutations identified were confirmed by direct DNA sequencing.

The 4154delA mutation carriers in the BRCA1 gene share a common ancestry.

Uncertainty exists whether the 4154delA mutation of the BRCA1 gene detected in unrelated individuals from Latvia, Poland and Russia is a founder mutation with a common ancestral origin. To trace back this problem we analysed the mutation-associated haplotype of the BRCA1 intragenic SNPs as well as intragenic and nearby STR markers in mutation carriers from the aforementioned populations. The mutation-associated SNP alleles were found to be "T-A-A-A-A-G" for six intragenic SNPs of the BRCA1 gene (IVS8-58delT, 3232A/G, 3667A/G, IVS16-68A/G, IVS16-92A/G, IVS18+66G/A, respectively).

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

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.