Selected aspects of inherited susceptibility to prostate cancer and tumours of different site of origin

Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of prostate cancer, but the genes which underlie the inherited susceptibility are elusive. The most compelling associations to date are with genes involved in DNA damage repair, including BRCA2. In Poland we have initiated a programme to identify DNA variants which confer an increased risk of prostate cancer and other cancers. Here we review our recent results. We found that germline mutations in BRCA1, CHEK2 and NBS1 confer an increased prostate cancer risk in Polish men. We provide evidence that CHEK2 is a multi-organ cancer susceptibility gene. We show that inherited variation in RNASEL and MSR1 genes do not contribute to prostate cancer development in Poland

Antigens HLA-G, sHLA- G and sHLA- class I in reproductive failure.

It can be supposed that relation between HLA-G polymorphism and sHLA-G protein expression are associated with successful embryo implantation and pregnancy maintenance. The aim of the study was the estimation specific differences in expression of sHLA-G and sHLA- class I antigens in women with reproductive failure in comparison with fertile women. The study sample enrolled 80 women, divided into 2 groups. The study group (B) enrolled 60 women with reproductive failure including 20 women with 3 recurrent spontaneous abortions in the first trimester of pregnancy (RSA), 20 women with empty sac (ES) and 20 women with 3 consecutive in-vitro fertilization failures (IVFf). The control group (C) enrolled 20 fertile women with at least 2 children. Soluble HLA- class I antigens (sHLA-I) and soluble HLA-G (sHLA-G) were determined using ELISA test kits from IBio Vendor Labolatory Medicine, Inc. HLA-G allele found in individuals in our study were identified by comparing the obtained bp sequences of exon 2., 3. and 4. with bp sequences of HLA-G antigen published at the Nolan Research Institute website. The highest concentration of sHLA-I is noted among women with HLA-G 10401 allele which differed significantly for the mean sHLA-I concentration calculated for all the remaining alleles (

Case report of a woman with monoclonal gammapathy and papillary thyroid carcinoma, diagnosed because of detection of CHEK2 (I157T) mutation in genetic examinations

The CHEK2 gene encodes the CHK2 protein, which is kinase involved in DNA repair processes. By activating a lot of cell substrates, it can regulate the cell cycle, demonstrates suppressive effects, and participates in the senescence and apoptosis processes. Mutations in the CHEK2 gene are associated with increased risk of numerous cancers. The case described herein is that of a woman with a missense mutation that results in the substitution of isoleucine for threonine at position 157. This variant of the mutation doubles the risk of papillary thyroid carcinoma two times and causes up to 9% of these cancer. It is also associated with a two-fold increased risk of cancers of the kidney (10%), colon (10%), and ovary (10% - G1), a 1.6-fold increased risk of prostate cancer (8% of all of them and 12% of familiar ones), and a 1.5-fold increased risk of breast cancer (7%). The screening procedures were initiated in a carrier who revealed papillary thyroid carcinoma. Genetic screening of the family diagnosed her daughter as the carrier of this mutation. Until now no active cancer disease has been recognized in the daughter. On the example of the presented case we discuss indications for screening in cases of positive family history. The group especially predisposed seem to be patients with at least two coexisting carcinomas. Having diagnosed the mutation, it is necessary to do genetic screening of family members. Continuous oncological observation of the carriers of CHEK 2 mutation is essential. (Pol J Endocrinol 2010; 61 (5): 502-506)Ludzki gen CHEK2 koduje białko CHK2, będące kinazą efektorową zaangażowaną w naprawę DNA. Aktywując wiele substratów komórkowych, bierze udział w regulacji cyklu komórkowego, wykazuje działanie supresyjnie, wpływa również na proces apoptozy i starzenia się komórek. Mutacje genu CHEK2 są związane z ryzykiem licznych nowotworów. Opisywany przypadek chorej dotyczy mutacji typu missens, gdzie dochodzi do zamiany izoleucyny na treoninę w pozycji 157. Mutacja ta zwiększa 2-krotnie ryzyko raka brodawkowatego tarczycy. Predysponuje do występowania 2-krotnie częściej raka nerki (10%), jelita grubego (10%), jajnika (10% - G1), 1,6-krotnie częściej raka prostaty (8% wszystkich i 12%występujących rodzinnie) oraz 1,5-krotnie częściej raka piersi (7%). Na podstawie diagnostyki w kierunku predysponowanych nowotworów wykryto u chorej raka brodawkowatego tarczycy. Skrining genetyczny rodziny pozwolił na wykazanie nosicielstwa tej mutacji u córki pacjentki - dotychczas nie stwierdzono u niej czynnej choroby nowotworowej. Opisywany przypadek chorej wskazuje na celowość przeprowadzania badań genetycznych w przypadku dodatniego wywiadu rodzinnego w kierunku chorób nowotworowych. Szczególnie predysponowaną grupą wydają się być chorzy z co najmniej dwoma współistniejącymi nowotworami. Wykazanie mutacji nakłada obowiązek badań genetycznych u pozostałych członków rodziny, jak również bezterminowy nadzór onkologiczny u nosicieli mutacji. (Endokrynol Pol 2010; 61 (5): 502-506

Large deletion causing von Hippel-Lindau disease and hereditary breast cancer syndrome

Patients with intragenic mutations of the VHL gene have a typical disease presentation. However in cases of large VHL gene deletions which involve other genes in the proximity of the VHL gene a presentation of the disease can be different. To investigate whether large VHL deletions that remove the FANCD2 gene have an effect on the disease phenotype, we studied a family with a 50 kb large deletion encompassing these two genes. Four patients in this family were affected by VHL-related lesions. However one carrier of the deletion also had bilateral ductal breast cancer at age 46 and 49. Both tumors were of ~2 cm in diameter. On one side lymph nodes were affected. One tumor was ER- and PR-negative (HER2 s unknown) and the second was ER- and PR-positive, and HER2-negative. Our study suggests that a deletion of FANCD2 gene, an important gene in the DNA repair pathway, may be associated with an increased risk of breast cancer, but further studies are needed in this regard