Date Published: , 2010
Publisher: A.I. Gordeyev
Author(s): A.P. Sokolenko, A.G. Iyevleva, N.V. Mitiushkina, E.N. Suspitsin, E.`V. Preobrazhenskaya, E.Sh. Kuligina, D.A. Voskresenskiy, O.S. Lobeiko, N.Yu. Krylova, T.V. Gorodnova, K.G. Buslov, E.M. Bit-Sava, G.D. Dolmatov, N.V. Porhanova, I.S. Polyakov, S.N. Abysheva, A.S. Katanugina, D.V. Baholdin, G.A. Yanus, A.V. Togo, V.M. Moiseyenko, S.Ya. Maximov, V.F. Semiglazov, E.N. Imyanitov.
Hereditary breast-ovarian cancer syndrome contributes to as much as 5–7% of breast cancer (BC) and 10–15% of ovarian cancer (OC) incidence. Mutations in the “canonical” genesBRCA1andBRCA2occur in 20–30% of affected pedigrees. In addition toBRCA1andBRCA2 mutations, germ-line lesions in theCHEK2,NBS1, andPALB2genes also contribute to familial BC clustering. The epidemiology of hereditary breast-ovarian cancer in Russia has some specific features. The impact of the “founder” effect is surprisingly remarkable: a single mutation,BRCA15382insC, accounts for the vast majority ofBRCA1defects across the country. In addition, there are two other recurrentBRCA1alleles:BRCA14153delA andBRCA1185delAG. BesidesBRCA1, in Russia breast cancer is often caused by germ-line alterations in theCHEK2andNBS1genes. In contrast toBRCA1andBRCA2, theCHEK2andNBS1heterozygosity does not significantly increase the OC risk. Several Russian breast cancer clinics recently started to investigate the efficacy of cisplatin in the therapy ofBRCA1-related cancers; initial results show a unique sensitivity ofBRCA1-associated tumours to this compound.
Breast cancer (BC) and ovarian cancer (OC) contribute significantly to cancer incidence and mortality. BC is the most frequent malignant pathology in women, with the lifetime risk reaching approximately 10%. In some cases, BC can be easily diagnosed at early stages and ultimately cured. Unfortunately, even with the implementation of total population screening, the BC related mortality rate has not decreased significantly, due to insufficient sensitivity of available diagnostic methods, as well as the high metastatic potential of some BC forms . OC is a much rarer disease than BC, being found only in 1.5% of women around the world; however, it is almost always diagnosed at late (incurable) stages. Early ovarian tumours do not cause symptoms and are often missed by ultrasound examination and СА-125 biomarker assay . Both BC and OC are diseases of the reproductive system; therefore, their hormonal, metabolic, and behavioural risk factors are common to a certain extent. Interestingly, these two diseases are the main components of the most frequent genetic disease – hereditary breast-ovarian cancer (HBOC) syndrome .
In Russia, the studies of the HBOC syndrome were initiated later than in the U.S. and Europe but they produced rather unexpected results. The first paper published in 1997 reported on the results obtained in patients with familial OC living in Moscow and several other regions of the former Soviet Union , the main result being the extremely high frequency of the BRCA1 5382insC mutation. As was mentioned above, this mutation had been first found in Jewish women; therefore, it had been for many years considered in the context of that particular ethnic group . However, it appeared that the BRCA1 5382insC mutation was not of Jewish origin. This mutation is found not only in females living in various regions of Russia, but also in native populations of Poland, Lithuania, Latvia, and Belarus [14–17]. It is perhaps more accurate to say that the BRCA1 5382insC mutation is of Slavic origin, and that the relatively high frequency of this mutation in Ashkenazi Jews observed mostly in Eastern Europe is likely due to the long coexistence of the Slavic and Jewish peoples in the Baltic region and adjacent territories.
The main goal of hereditary cancer syndrome diagnostics is to find healthy women with corresponding mutations. It is believed that timely detection of the genetic defect can help to avoid fatal cancer outcome. Women with heterozygous BRCA1 and BRCA2 genes are under regular observation for early BC/OC diagnostics. In addition, preventive surgical removal of target tissues is recommended  to women with a BRC A mutation .