Background: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. Participants and methods: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. Results: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1GRA, 1100delC). Conclusion: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.

BackgroundVHL inactivation is the most established molecular characteristic of clear cell renal cell carcinoma (ccRCC), with only a few additional genes implicated in development of this kidney tumor. In recently published ccRCC gene expression meta-analysis study we identified a number of deregulated genes with limited information available concerning their biological role, represented by gene transcripts belonging to transmembrane proteins family (TMEMs). TMEMs are predicted to be components of cellular membranes, such as mitochondrial membranes, ER, lysosomes and Golgi apparatus. Interestingly, the function of majority of TMEMs remains unclear. Here, we analyzed expression of ten TMEM genes in the context of ccRCC progression and development, and characterized these proteins bioinformatically.MethodsThe expression of ten TMEMs (RTP3, SLC35G2, TMEM30B, TMEM45A, TMEM45B, TMEM61, TMEM72, TMEM116, TMEM207 and TMEM213) was measured by qPCR. T-test, Pearson correlation, univariate and multivariate logistic and Cox regression were used in statistical analysis. The topology of studied proteins was predicted with Metaserver, together with PSORTII, Pfam and Localizome tools.ResultsWe observed significant deregulation of expression of 10 analyzed TMEMs in ccRCC tumors. Cluster analysis of expression data suggested the down-regulation of all tested TMEMs to be a descriptor of the most advanced tumors. Logistic and Cox regression potentially linked TMEM expression to clinical parameters such as: metastasis, Fuhrman grade and overall survival. Topology predictions classified majority of analyzed TMEMs as type 3 and type 1 transmembrane proteins, with predicted localization mainly in ER.ConclusionsThe massive down-regulation of expression of TMEM family members suggests their importance in the pathogenesis of ccRCC and the bioinformatic analysis of TMEM topology implies a significant involvement of ER proteins in ccRCC pathology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1530-4) contains supplementary material, which is available to authorized users.

Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed - both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9-27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5-12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1-11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.

P=0.005). There was an inverse correlation with the percentage of gamma/delta T cells in PBL and the TIL median 26.7%). The cells possessing gamma/delta type T cell receptor accounted for a small fraction of concentration (K=−0.3, P<0.05). Conclusions The TIL immunophenotype is diÂerent from the T cells in PBL and TIL (median 5.6% and 3.7%). Tumour-infiltrating T lymphocytes had a significantly PBL and is influenced by the histological grade of the tumour. The activation of TIL and its relationship higher percentage of cells expressing human leucocyte antigen (HLA) DR (median 30.9%) and CD25 (median with tumour progression suggests that they might be sensitized and activated by tumour cells. 6.2%) antigens than the equivalent populations in peripheral blood from the same patient group Keywords Renal cell carcinoma, tumour infiltrating lymphocytes, immunology (P<0.001). The degree of T cell activation appeared ing on the influence of the tumour on lymphoid cells in

Leptin is an adipose tissue-secreted hormone that acts via specific receptors (Ob-R), of which six isoforms are at present recognized (from Ob-Ra to Ob-Rf). Ob-Rb is the only isoform able to activate JAK-STAT and MAPK signaling cascades. A large body of evidence suggests that leptin and its receptors are involved in prostate physiology and pathophysiology in humans, but studies on the leptin system in the rat prostate are lacking. Reverse transcription-polymerase chain reaction showed the expression of mRNAs of leptin, Ob-Ra, Ob-Rb, Ob-Rc, Ob-Re and Ob-Rf in adult rat seminal vesicles and prostate (coagulating, dorsal, ventral and lateral lobes). Western blotting demonstrated the presence in these specimens of the Ob-Rb protein, and immunocytochemistry revealed that Ob-Rb was mainly located in their epithelial-cell component. Collectively, these findings strongly suggest that leptin and Ob-R may be involved in the autocrine-paracrine functional regulation of the epithelial cells of adult rat seminal vesicles and prostate.