Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia. Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (< or =40 years) and/or family history). BC-associated alleles were revealed in 46 (15.2%) women. BRCA1 5382insC mutation was detected in 29 (9.6%) patients, CHEK2 1100delC in 9 (3.0%), BRCA1 4153delA in 3 (1.0%), CHEK2 IVS2+1G>A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests.

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This study was aimed to assess the role of CHEK2 1100delC mutation in breast cancer (BC) predisposition in Russia. The 1100delC allele was detected in 14/660 (2.1%) unilateral BC cases and in 8/155 (5.2%) patients with the bilateral form of the disease, but only in 1/448 (0.2%) middle-aged control females and in none of 373 elderly tumor-free women. The obtained data point at potentially high clinical relevance of CHEK2 1100delC testing in females of Russian origin and warrant similar case-control studies in ethnically and geographically related regions, especially in Ukraine, Belarus and Baltic countries.

The BRCA1 4153delA allele is frequently referred to as the Russian founder mutation, as it was initially detected in several cancer families from Moscow. Our earlier studies have demonstrated 1% occurrence of BRCA1 4153delA heterozygosity in familial and/or early-onset and/or bilateral Russian breast cancer (BC) patients. Since literature data suggest that the 4153delA variant is more associated with ovarian cancer (OC) than with BC, we expected to reveal a highly elevated frequency of this genotype in Russian ovarian cancer series. However, real-time allele-specific PCR genotyping has detected only two BRCA1 4153delA carriers out of 177 unselected OC patients (1.1%). Both these carriers were early-onset and had serous carcinomas of grade 3. Thus, our study supports neither the Russian origin of BRCA1 4153delA mutation, nor its selectivity towards ovarian versus breast cancer predisposition.