PROSTATE CANCER AND HEREDITARY SYNDROMES

The aim of this study is to assess relative risk of prostate cancer (PC) and other tumors in families of patients with multiple primary malignancies (MPM) and the syndrome of hereditary nonpolyposis colorectal cancer (HNPCC). The study is based on data from the cancer register of families that includes information on 560 patients with MPM, 126 families with HNPCC and their first-degree relatives. Incidence of these diseases in population served as the control.

Among 560 probands with PPN 217 (38.7%) were male and 343 (61.3%) – female. Only 12 (2.1%) male patients had tumor in the prostate. In these patients 24 tumors were identified. Two patients had synchronous tumors, other ten patients had metachronous. Eight patients with prostate cancer had tumors of other organs: 5 – in rectum, 2 – in colon and 1 – in bladder. As a second tumor prostate cancer was diagnosed in 4 patients, three of them had rectal cancer and one – colon cancer. Only 2 (0.3%) patients had prostate cancer as a primary tumor. Clinical and genealogical information achieved from 543 patients with MPM, including in 206 male probands. Among 3637 first-degree relatives of probands with MPM prostate cancer was diagnosed in 2  (0.11±2.3%) patients that was 1.7 times higher than in population (0.063±0.0019%). The relative risk of prostate cancer for relatives of patients from families with HNPCC syndrome was 0.8 ± 6.3% that was 12/7 times higher than  in the control group (p <0.05). The estimation of the relative risk in families of male probands was perfprmed. Among 1460 male relatives with MPM only 1 (0.14%) case of prostate cancer was diagnosed (son of proband). Among 42 families of male probands with HNPCC syndrome, prostate cancer was detected in 2 (1.3%) brothers that exceeds population risk 20.6 times. Although the molecular mechanisms and pathogenesis of prostate cancer in such families is unknown, its association with a HNPCC-syndrome and possibly MPM-syndrome is obvious.

Higher relative risk of developing prostate cancer for male relatives of probands with MPM and HNPCC syndrome presupposes inherited genetically determined predisposition to disease development. Further molecular and genetic studies are needed to determine the genetic basis of predisposition to prostate cancer in these families.

1. Ahn J., Moslehi R., Weinstein S. J. et al. Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study //International Journal of Cancer. — 2008. — Vol.123, Issue 5. — P.1154–1159.

2. Alcaraz A., Hammerer P., Tubaro A. et al. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol. — 2009. — Vol.55, N4 864–873.

3. Altekruse S. F.,.Huang L., Cucinelli J. E., McNeel T.S., Wells K. M., Oliver MN. Spatial patterns of localized-stage prostate cancer incidence among white and black men in the southeastern United States, 1999–2001 //Cancer Epidemiol Biomarkers Prev. —2010. — Vol.19. — P.1460–1467.

4. Bauer C. M., Ray A. M., Halstead-Nussloch B.A., et al.: Hereditary prostate cancer as a feature of Lynch syndrome. Fam Cancer. —2011. — Vol.10. — Issue 1. — P.37–42.

5. Beebe-Dimmer J.L., Drake E. A., Dunn R. L., Bock C. H., Montie J. E., Cooney K. A. Association between family history of prostate and breast cancer among African-American men with prostate cancer. // Urology. —2006. — Vol.68, N5. — P.1072–1076.

6. Boyle P., Ferlay J. Cancer incidence and mortality in Europe 2004 //Ann. Oncol.—2005.— Vol.16, N3.— P.481–488.

7. Brandt A., Bermejo J. L., Sundquist J., Hemminki K. Age-Specific Risk of Incident Prostate Cancer and Risk of Death from Prostate Cancer Defined by the Number of Affected Family Members //European Urology. —2010. — Vol. 58, Issue 2. — P. 275–280.

8. da Silva F. C., de Oliveira L. P., Santos E. M. et al. Frequency of extracolonic tumours in Brazilian families with Lynch syndrome: Analysis of a hereditary colorectal cancer institutional registry. Fam Cancer. — 2011. — Vol.9. — P. 563–570.

9. Eeles R. A., Kote-Jarai Z., Giles G. G. et. al. Multiple newly identified loci associated with prostate cancer susceptibility //Nat Genet. —2008. — Vol.40, N3. — P.316–321.

10. Fabbri C., Ravaioli A., Ravaioli A. Risk of cancer of the prostate and of the kidney parenchyma following bladder cancer //Tumori. —2007. — Vol.93, N2. — P.124–128.

11. Fitzgerald L. M., Kwon E. M., Koopmeiners J. S. et al. Analysis of recently identified prostate cancer susceptibility loci in a population-based study: associations with family history and clinical features //Clin Cancer Res. —2009. — Vol.15, Issue 9. — P.3231–3237.

12. Grindedal E. M., M ller P., Eeles R. et al. Germ-Line Mutations in Mismatch Repair Genes Associated with Prostate Cancer //Cancer Epidemiol Biomarkers Prev. —2009. — Vol.18, Issue 9. — P.2460–2467.

13. Gronberg H., Bergh A., Damber J. E., Emanuelsson M. Cancer risk in families with hereditary prostate carcinoma //Cancer. —2000. — Vol.89, Issue 6. — P. 1315–1321.

14. Gursel B., Meydan D., zbek N. et al. Multiple Primary Malignant Neoplasms from the Black Sea Region of Turkey //The Journal of International Medical Research. —2011. — Vol.39. — P.667–674.

15. Isom-Batz G., Bianco F. J., Kattan M. W., Mulhall J. P., Lilja H., Eastham J. A. Testosterone as a predictor of pathological stage in clinically localized prostate cancer //J Urol. —2005;173, Issue 6. — P.1935–1937.

16. Jemal A., Siegel R., Ward E. et al. Cancer statistics. —2008 CA //Cancer J. Clin. —2008. — Vol.58, N2. — P.71–96.

17. Kellen E., Zeegers M. P., Dirx M. et al. The occurrence of both bladder and prostate cancer in five cancer registries in Belgium, The Netherlands and the United Kingdom //