Immunogenetics of prostate cancer and benign hyperplasia--the potential use of an HLA-G variant as a tag SNP for prostate cancer risk.

Human leukocyte antigen G (HLA-G) is an immunomodulatory molecule with important roles both physiologically as well as an escape mechanism of cancer cells. In this study, we evaluated the impact of eight polymorphisms at the 3' untranslated region (3'UTR) of the HLA-G gene in the development of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). A total of 468 DNA samples of Brazilian men predominantly Euro-descendant with PCa (N = 187), BPH (N = 152) and healthy control individuals (N = 129) were evaluated. The HLA-G 3'UTR region was amplified by polymerase chain reaction (PCR), sequenced and genotyped to identify the 14 bp insertion/deletion (rs371194629), +3003T/C (rs1707), +3010C/G (rs1710), +3027A/C (rs17179101), +3035C/T (rs17179108), +3142G/C (rs1063320), +3187A/G (rs9380142) and +3196C/G (rs1610696) polymorphisms. Regression logistic and chi-square tests were performed to verify the influence of single nucleotide polymorphisms (SNPs) in PCa and/or BPH susceptibility, as well as in PCa progression (clinicopathological status). Our data showed the UTR-4 haplotype as a risk factor to PCa in comparison with control [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.39-3.96, P adjusted = 0.003) and BPH groups (OR 1.82, 95% CI 1.15-2.86, P adjusted = 0.030). Further, the 'non-14bp Ins_ + 3142G_+3187A' haplotype (OR 1.56, 95% CI 1.10-2.20, P adjusted = 0.036), the +3003CT genotype (OR 4.44, 95% CI 1.33-4.50, P adjusted = 0.032) and the +3003C allele (OR 2.33, 95% CI 1.38-3.92, P adjusted = 0.016) also conferred susceptibility to PCa. Our data suggest an important influence of HLA-G 3'UTR polymorphisms in PCa susceptibility and support the use of the +3003 variant as a tag SNP for PCa risk.

Is there any association between TACSTD2, KIAA1253, Ku70 and mutant KRAS gene expression and clinical-pathological features of colorectal cancer?

AIM: To determine the quantitative gene expression of KRAS codon 12 mutant, TACSTD2, Ku70 and SERIN1 in samples of tumor tissue and to relate them with clinical-pathological characteristics of colorectal cancer. METHODS: Samples of tumor and normal tissue of patients surgically treated for colorectal cancer between July 2005 and July 2009 were stored in a tissue bank. These samples were studied with the technique of real-time polymerase chain reaction in respect to expression of the following genes: KRAS codon 12 mutation, TACSTD2, Ku70, and SERIN1. RESULTS: Tumor samples of 37 patients were studied. The mean age was 65.5 years. Twenty one patients (56.8%) were male. Nine patients (24.3%) were classified as TNM stage I, 11 patients (29.8%) as TNM stage II, eight patients (21.6%) as TNM stage III and nine patients (24.3%) as TNM stage IV. The Ku70 expression in poorly-differentiated tumors is significantly higher than in well and moderately-differentiated tumors (2.76 vs. 1.13; p < 0.05). SERIN1, TACSTD2 and KRAS codon 12 mutation are not associated with clinical-pathological characteristics of colorectal cancer. CONCLUSION: Ku70 expression in poorly-differentiated tumors is significantly higher than in well and moderately-differentiated colorectal tumors.