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N6 BRCA2 gene mutation characterization in hereditary prostate cancer patients in Latvia

      Introduction and Objectives

      Prostate cancer is one of the most commonly diagnosed tumors affecting men in Latvia. A significant factor in prostate cancerogenesis is genetic. The failure to identify highly penetrant genes in hereditary prostate cancer may result from the fact that multiple genes with a small to moderate effect are involved. Aim of the study is to evaluate the epidemiological features and BRCA2 gene mutation variations in hereditary prostate cancer in Latvia, as well as to consider association with other malignancies.

      Material and Methods

      In total 855 prostate cancer families were selected for our study that was identified from Nov-2003 to Jan-2009. Data were collected on their clinical characteristics; additionally blood samples were collected for DNA tests. Family cancer histories were analyzed according to clinical diagnostic criteria of hereditary prostate cancer, if at least one of the following criteria applied: (a) at least 3 affected blood relatives at any age; or (b) 2 affected blood relatives at age ≤55 years. Complete sequencing of the BRCA2 gene was performed for 9 probands from selected hereditary prostate cancer families.

      Results

      855 family histories of prostate cancer patients were analyzed; from those 11 (1.3%, 95% CI: 0.7–2.3) families matched clinical diagnostic criteria of hereditary prostate cancer. The median age at diagnosis in this group was 65.4 (range 54–74) years. Besides BRCA2 polymorphisms in all analyzed cases, the novel missence mutation V2419D was detected in 73 years old proband with family history of 2 prostate, 1 lung and 1 stomach cancer. Along with prostate cancer at least 1 other localization malignancy was found among blood relatives in 9 (81.8%, 95% CI: 52.3–94.9) families of hereditary prostate cancer group. Distribution of the most frequent malignancies are: lung in 4 (36.4%) cases, uterine in 3 (27.3%) cases, stomach in 2 (18.2%) cases, breast in 2 (18.2%) cases, kidney in 1 (9.1%) case, leukemia in 1 (9.1%) case, unknown in 1 (9.1%) case.

      Conclusions

      Hereditary prostate cancer according to definitive clinical diagnostic criteria was found in 1.3% (95% CI: 0.7–2.3) of prostate cancer cases in Latvia. Further research of first degree family members and control group needed to confirm clinical significance of detected novel missense mutation V2419D in predisposition to hereditary prostate cancer and other localization malignancies.