HEALTH OF WOMAN. 2016.2(108):155–159; doi 10.15574/HW.2016.108.155 
 

Frequency and characteristics of family cancer syndrome in ovarian cancer patients.
 

Palyichuk O. V.

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Ukraine, Kyiv

CE «Cherkassy Regional Oncologic Dispensary» of Cherkassy Regional Council, Ukraine

The aim of the study: to assess the results of clinical, clinical-genealogical and molecular-genetic examination of OC patients and to substantiate its role as an important step for creation of genetic risk groups of developing neoplasia in the family.

Materials and methods. The results of comprehensive clinical, clinical-genealogical and molecular-genetic examinations of 158 patients with OC, stage І–ІV are presented. It was found that in probands’ families (OC patients) malignant tumors of female reproductive system, gastro-intestinal tract and other were prevailing that conform to Lynch syndrome type II (family cancer syndrome).

Results. Among the tumors of female reproductive system ovarian cancer was diagnosed in 27.5%, breast cancer – in 16.1%, uterine cancer – in 8.1%, and tumors of gastro-intestinal tract – in 20.2% of cases. Accordingly to family trees data cancer was more common in proband’s mothers (35.5%), grandmothers (29.9%), and aunts (11.6%), and male relatives (19.8%). Molecular-genetic examination of genomic DNA of peripheral blood revealed 5382insC mutation in BRCA1 gene in 9 patients with serous OC, 5 from them had family cancer syndrome. Mutation 6174delT in BRCA2 gene in this clinical material was not detected. Germinal mutations in indicated suppressor genes are predictive factors of neoplasia development in family and proband’s progeny and suggest the phenomenon of genetic predisposition to cancer development in the family.

Conclusions. Family cancer history that is determined by clinical-genealogical analysis of the family is an important component in diagnostics of hereditary/non-hereditary variants of OC and creation of genetic risk groups for cancer development in the family with family cancer syndrome. Germinal mutation 5382insC in the gene BRCA1 is a predictive factor of neoplasia development in proband’s progeny and suggests the phenomenon of genetic predisposition to cancer development in the family. Clinical-genealogical examination can be assessed as an integral part of diagnostic and preventive work of gynecologists, oncogynecologists and oncogenetics.

Key words: ovarian cancer, family cancer syndrome, mutations in BRCA1 and BRCA2 genes.

REFERENCES

1. Vorobiev LI, Turchak OV, Svintsitskyi VS and others. 2009. The problem of recurrence of gynecological cancer. 7 women health (43, 2): 72-75.

2. Svintsitskyi VS. The results of the 2007 primary cyto-reductive operations in patients with malignant tumors of the ovary. Oncology 9 (3): 222-228.

3. Svintsitskyi VS. 2010. longstanding form of malignant ovarian tumors: increased resectable tumors by retro-peritoneal and pelvic total hysterectomy perytoneoectomy (duhlasectomy). Oncology 12 (2): 38-40.

4. Svintsitskyi VS. 2010. Integrated treatment of patients with malignant tumors of the ovary. Author. Dis. Dr. med. Science. K: 40.

5. Chen S, Parmigiani G. 2010. Meta-analysis of BRCA1 and BRCA2 penetrance. J. Clin. Oncol. 25(11):1329–1333.

6. Couch FJ, Gaudet MM, Antoniou AC et al. 2010. Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol. Biomarkers Prev. 21(4):645–57. http://dx.doi.org/10.1158/1055-9965.EPI-11-0888; PMid:22351618 PMCid:PMC3319317

7. Zhong Q, Peng HL, Zhao X et al. 2015. Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis. Clin. Cancer Res. 21(1):211–20. http://dx.doi.org/10.1158/1078-0432.ccr-14-1816

8. Sowter HM, Ashworth A. 2010. BRCA1 and BRCA2 as ovarian cancer susceptibility genes. Carcinogenesis 26(10):1651–1656.

9. Jelovac D, Armstrong DK. 2011. Recent progress in the diagnosis and treatment of ovarian cancer. CA: A Cancer Journal for Clinicians 63(3):183–203. http://dx.doi.org/10.3322/caac.20113

10. Weissman SM, Burt R, Church J et al. 2012. Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National society of genetic counselors and the collaborative group of the Americas on inherited colorectal cancer joint practice guideline. J. Genet. Couns. 21(4):484–93. http://dx.doi.org/10.1007/s10897-011-9465-7

11. Russo A, Calт V, Bruno L et al. 2010. Hereditary ovarian cancer. Critical Reviews in Oncology. Hematology 69(1):28–44.

12. Kluska A, Balabas A, Paziewska A et al. 2015. New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian cancer detected by next generation sequencing. BMC Med. Genomics. 8(19). http://dx.doi.org/10.1186/s12920-015-0092-2.

13. Sekine M, Nagata H, Tsuji S. 2001. Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population. Clin. Cancer Res. 7(10):3144–3150.

14. Tung N, Battelli C, Allen B et al. 2015. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 121(1):25–33.

15. Howarth DR, Lum SS, Esquivel P et al. 2015. Initial Results of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome. Am. Surg. 81(10):941–4.

16. Shih I-M, Kurman RJ. 2005. Ovarian Tumorigenesis. A Proposed Model Based on Morphological and Molecular Genetic Analysis. Amer. J. Pathol. 164(5):1511–1518.

17. Lim D, Oliva E. 2003. Precursors and pathogenesis of ovarian carcinoma. Pathology. 45(3):229–42. http://dx.doi.org/10.1097/PAT.0b013e32835f2264; PMid:23478230

18. Trivers KF, Baldwin LM, Miller JW et al. 2011. Reported referral for genetic counseling of BRCA1/2 testing among United States physicians: a vignette-based study. Cancer. 117:5334–43. http://dx.doi.org/10.1002/cncr.26166; PMid:21792861

19. Wood ME, Kadlubek P, Pham TH et al. 2014. Quality of cancer family history and refeerral for genetic counseling and testing among oncology practoces: a pilot test of quality measures as part of the Americam society of clinical oncology quality oncology practice initiative. J. Clin. Oncol. 32(8):824–829.

20. Wood ME, Flinn BS, Snockdale S. 2013. Primary care physician management, referral, and relations with specialists concerning patients at risk for cancer due to family history. Public health gonomics 16:75–82. http://dx.doi.org/10.1159/000343790; PMid:23328214

21. Lu KH, Wood ME, Daniels M et al. 2014. American Society of Clinical Oncology expert statement: Collection and use of a cancer family history for oncology providers. J. Clin. Oncol. 32:833–840. http://dx.doi.org/10.1200/JCO.2013.50.9257; PMid:24493721 PMCid:PMC3940540

22. Stadler ZK, Schrader KA, Vijai J et al. 2014. Cancer genomics and inherited risk. J Clin. Oncol. 32:687–698. http://dx.doi.org/10.1200/JCO.2013.49.7271; PMid:24449244