Virtually all known tumor predisposing genes have been identified via the analysis of familial cancer cases. Here we argue that this approach is likely to miss recessively acting cancer genes and suggest the analysis of family history-negative patients with multiple primary malignancies for identifying homozygous at-risk genotypes. We performed calculations showing that the homozygous carriers of rare recessive cancer predisposing alleles are unlikely to report a family history of the disease. We further revealed that the c.2515_2519delAAGTT homozygous mutation in a Holliday junction resolvase, GEN1, was overrepresented in women with bilateral breast cancer (BC) as compared to healthy controls [11/360 (3.1 %) vs. 18/1305 (1.4 %); odds ratio (OR) = 2.25 (1.02-4.75); p = 0.031], although this trend was not maintained in unilateral BC patients [23/1851 (1.2 %)]. Noticeably, presence of biallelic c.2515_2519delAAGTT mutation was associated with the absence of BC in mother both in bilateral and unilateral BC cases [7/239 (3.0 %) vs. 0/41 (0 %) and 21/1,558 (1.3 %) vs. 0/215 (0 %), respectively; Mantel-Haenszel p = 0.041]. Thus, this study suggests that identification of dominant and recessive cancer predisposing genes may require distinct study groups.

The purpose of the study was to analyze the incidence of primary-multiple cancer (PMC) of the female reproductive system according to the population cancer register of the Chelyabinsk region for 15 years (1999-2013) using the example of PMC of the cervix. Carry out an analysis of the adjusted cumulative survival in the group of patients with PMC of the cervix as compared with solitary cervical cancer.Material and methods. The material was processed using the classification of Zisman I. F. and Kirichenko G. D. (1978) on the sequence of tumors: metachronous, synchronous, mechatronic-synchronous and synchronous-metachronous. The interval of metachronousness is 6 months. The survival rates of cancer patients in the Chelyabinsk region were calculated automatically with the use of the computer program "Calculation of survival rates" — an application to the population-based cancer registry of OOO Novell-SPb. Using the method of continuous sampling, we carried out a retrospective analysis of the case histories of patients with PMC of the female reproductive system treated in the SBEO CRCOD for 15 years (1999-2013).Results. During the period under review, 82 patients with PMC of the cervix uteri were examined, metachronous tumors prevailed in 55 (67.1%), synchronous tumors developed in 27 (33.75%). In the group of metachronous tumors in 12 (21.8%) patients had a combination of three tumors. Three (5.45%) patients had a combination of four tumors. Analysis of combinations of cervical cancer showed that more often, the cervical cancer metachronically met with breast cancer 35% (14 patients), endometrial cancer 17.5% (7 patients), ovarian cancer 7.5% (3 patients). Synchronously cervical cancer was more often combined with breast cancer 42.8% (9 patients), endometrium 28.6% (6 patients), ovaries 23.8% (5 patients) and rectal cancer 4.8% (1 patient).The results of calculation of the index of the adjusted cumulative survival of the study group of the PMC of the cervix showed that in the group of metachronous tumors, survival rates were significantly higher than in the group of synchronous tumors: single-year survival was 84.8 ± 6.3% against 82.4 ± 9.2, three-year survival — 66.8 ± 7.8% against 47, 1 ± 12.1, and five years after the diagnosis, 53.8 ± 8.6% of patients survived.Conclusion. Thus, patients with cervical cancer are at risk of developing cancer of other localizations that share common etiopathogenetic factors, such as HPV infection in women, hormonal disorders.

The problem of primary multiplicity of malignant tumors remains relevant in oncology due to the growing number of patients with polyneoplasia, especially for tumors of the female reproductive system. The analysis of the frequency and combinations of polyneoplasias of the reproductive system in women on the example of primary multiple ovarian cancer according to the data of the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine for 15 years. The calculated indicators of the adjusted cumulative survival of patients with polyneoplasia and solitary ovarian cancer were calculated. The data obtained can be used in clinical practice, as the primary and secondary prevention of cancer in women.

The problem of primary multiplicity of malignant tumors remains actual in oncology due to growing number of patients with polyneoplasia especially of the breast. Modern genetic studies use “genetically enriched” cases of cancer, which include in particular primary-multiple malignant tumors of the breast. Practically every tumor has an individual set of somatic mutations and genetic mechanisms of breast cancer appearance are very different. The multicentre study shows the role of recessive determinants of the predisposition to bilateral breast cancer without a family history. The obtained data could be used in clinical practice as a secondary prevention of breast cancer.

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