Interleukin-6 (IL-6), a pro-inflammatory cytokine, is involved in prostate cancer progression, including androgen independence. Serum IL-6 levels also correlate with prostate tumor burden, prostate-specific antigen levels and metastasis. Since circulating cytokine levels vary considerably inter-individually, such variation could be linked to genetic factors, including genetic polymorphism. The -174G>C/rs1800795 polymorphism in the IL-6 promoter is functionally relevant in terms of transcriptional regulation and disease association. We investigated a possible association of the -174G/C polymorphism with prostate cancer. Since significant racial disparities exist in prostate cancer incidence, we also investigated this association between the -174G/C polymorphism and prostate cancer in Caucasians and African-Americans, separately. Direct sequencing of the PCR amplicon from genomic DNA was used for genotyping rs1800795 in all subjects [age-matched controls (N = 140) and prostate cancer patients (N = 164)]. Sample size and power was calculated using the PGA software. We found the GG genotype to be associated with increased risk of prostate cancer in Caucasian subjects, whereas the CC genotype was associated with increased risk in the African-American sample set. Such a dimorphic genotypic association with cancer and race is unique and suggests a complex gene-gene and gene-environment interaction.

Background 2′ -5′ –oligoadenylate synthetase (2-5 OAS1), an antiviral, pro-apoptotic and anti-proliferative gene converts ATP to a series of 2′ -5′ –oligoadenylates (2-5A). 2-5A in turn activates RNaseL, a candidate hereditary prostate cancer gene. OAS1 polymorphism (rs2660) has been associated with increased susceptibility to infections and various diseases. In general, the low enzyme activity AA genotype promotes susceptibility whereas high enzyme activity GG genotype confers protection. In this study we investigated the association of this functional polymorphism (rs2660) in OAS1 with prostate cancer. Methods Sample size and power was calculated using the PGA software. Genomic DNA from a controls (n=140) and prostate cancer patients (n=164) were used for genotyping SNPs rs2660, rs1131454 and rs34137742 on all samples. Statistical analysis was performed using logistic regression model. Results Significant association was observed between rs2660 genotype (A/G) and prostate cancer. Genotype AA increased the risk whereas GG genotype decreased the risk of prostate cancer. The GG genotype was not observed in the African American samples. The AA genotype also increased the risk of prostate cancer with age. Conclusions OAS1 SNP rs2660 AA genotype is significantly associated with prostate cancer whereas GG genotype protects against prostate cancer. OAS1 rs2660 could be a prostate cancer susceptibility polymorphism, a significant observation especially in a context of the OAS1-RNaseL pathway. Thus a functional defect in OAS1 due to rs2660 SNP can not only attenuate RNaseL function, but can also alter cell growth and apoptosis independent of RNaseL.

Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared with Caucasian (CA) men in the United States. Transforming growth factor β (TGFβ) signaling pathway is linked to health disparities in AAs. Recent studies suggest a role of TGFβ3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in PCa in AA men has not been studied. We determined the circulating levels of TGFβ3 in AA and CA men diagnosed with PCa using ELISA. We analyzed serum samples from both AA and CA men diagnosed with and without PCa. We show that AA PCa patients had higher levels of TGFβ3 protein compared with AA controls and CA patients. In fact, TGFβ3 protein levels in serum were higher in AA men without PCa compared with the CA population, which may correlate with more aggressive disease seen in AA men. Studies on AA-derived PCa cell lines revealed that TGFβ3 protein levels were also higher in these cells compared with CA-derived PCa cell lines. Our studies also reveal that TGFβ does not inhibit cell proliferation in AA-derived PCa cell lines, but it does induce migration and invasion through activation of PI3K pathway. We suggest that increased TGFβ3 levels are responsible for development of aggressive PCa in AA patients as a consequence of development of resistance to inhibitory effects of TGFβ on cell proliferation and induction of invasive metastatic behavior.

RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling to address the broad area of multi-scalar cellular communication by miRNAs. We show that spatial partitioning of miRNAs is related to sequence similarity to the overall transcriptome. This has broad implications in biological informatics for gene regulation and provides a deeper understanding of nucleotide sequence structure and RNA language meaning for human pathologies resulting from changes in gene expression.

BackgroundTo date there has not been any nationwide age-standardized incidence data reported for prostate cancer in Nigeria. We examined and integrated diverse trends in the age-specific incidence of prostate cancer into a comprehensive trend for Nigeria, and examined how best the existing data could generate a countrywide age-standardized incidence rate for the disease.MethodsData were obtained from studies undertaken between 1970 and 2007 in referral hospital-based cancer registries. Records from at least one tertiary hospital in each of the six geopolitical zones of Nigeria were examined retrospectively. Data were also reported for the rural population in cross-sectional prospective studies. Age-standardized incidence rates and the annual incidence of disease were calculated.ResultsHigher incidence rates for prostate cancer during this period were recorded for patients aged 60–69 years and 70–79 years, with a lower incidence rate for patients aged younger than 50 years. An exponential annual incidence rate of disease was observed in the 50–79 year age group and peaked at 70–79 years before dropping again at age 80 years. The results showed metastasis in more than half of these hospital-based prostate tumors.ConclusionOur results suggest that prostate cancer occurs at a relatively young age in Nigerians and that hospital-based registry reports may not appropriately reflect the incidence of the disease in Nigeria. A countrywide screening program is urgently needed. Finally, the difference in reported stages of disease found in Nigerians and African-Americans versus Caucasians suggests biological differences in the prognosis. Nigeria may thus typify one of the ancestral populations that harbor inherited genes predisposing African-Americans to high-risk prostate cancer.

Background Myxovirus (influenza virus) resistance A (MxA) is an interferon stimulated antiviral protein that is required for a complete antiviral response. MxA polymorphism (rs2071430) is located within an Interferon Stimulated Response Element (ISRE) at position −88 in the gene’s promoter region, and it has been associated with increased susceptibility to infections and various diseases. In general, the low promoter activity genotype (GG) promotes susceptibility, whereas the high promoter activity genotype (TT) confers protection to Hepatitis C viral infection. MxA’s role in prostate cancer is not fully understood. Previous literature has shown that MxA may be a mediator of the effect of IFN on normal and tumor cell motility. MxA may act as a tumor suppressor and the level of expression may be a predictor of metastatic potential. Based on this information, in this study we investigated the association of this functional polymorphism (rs2071430) in MxA with prostate cancer. Methods Sample size and power was calculated using the PGA software. Genomic DNA from a controls (n=140) and prostate cancer patients (n=164) were used for genotyping SNP rs2071430 on all samples. Statistical analysis was performed using logistic regression model. Results A significant association was observed between rs2071430 genotype GG and prostate cancer. Individuals harboring the GG genotype are at an increased risk of prostate cancer. Data stratification reveals that the mutant GT genotype offers either offers some protection against prostate cancer in Caucasians. Conclusions MxA SNP rs2071430 GG genotype is significantly associated with prostate cancer irrespective of race. However, data stratification also suggests that the GT genotype is under-represented in Caucasian subjects suggesting its role in protection against prostate cancer in Caucasians. Although MxA is primarily implicated in viral infection, but it may be also be associated with prostate cancer. Recent studies have implicated viral and bacterial infections with increased prostate cancer risk. Expression of the high promoter activity genotype may offer resistance to prostate cancer infection and possibly influence clinical outcomes.

We devise an approach to Bayesian statistics and their applications in the analysis of the Monty Hall problem. We combine knowledge gained through applications of the Maximum Entropy Principle and Nash equilibrium strategies to provide results concerning the use of Bayesian approaches unique to the Monty Hall problem. We use a model to describe Monty's decision process and clarify that Bayesian inference results in an "irrelevant, therefore invariant" hypothesis. We discuss the advantages of Bayesian inference over the frequentist inference in tackling the uneven prior probability Monty Hall variant. We demonstrate that the use of Bayesian statistics conforms to the Maximum Entropy Principle in information theory and Bayesian approach successfully resolves dilemmas in the uneven probability Monty Hall variant. Our findings have applications in the decision making, information theory, bioinformatics, quantum game theory and beyond.

An in silico study of mRNA secondary structure has found a bias within the coding sequences of genes that favors "in-frame" pairing of nucleotides. This pairing of codons, each with its reverse-complement, partitions the 20 amino acids into three subsets. The genetic code can therefore be represented by a three-component graph. The composition of proteins in terms of amino acid membership in the three subgroups has been measured, and sequence runs of members within the same subgroup have been analyzed using a runs statistic based on Z-scores. In a GENBANK database of over 416,000 protein sequences, the distribution of this runs-test statistic is negatively skewed. To assess whether this statistical bias was due to a chance grouping of the amino acids in the real genetic code, several alternate partitions of the genetic code were examined by permuting the assignment of amino acids to groups. A metric was constructed to define the difference, or "distance", between any two such partitions, and an exhaustive search was conducted among alternate partitions maximally distant from the natural partition of the genetic code, to select sets of partitions that were also maximally distant from one another. The statistical skewness of the runs statistic distribution for native protein sequences were significantly more negative under the natural partition than they were under all of the maximally different partition of codons, although for all partitions, including the natural one, the randomized sequences had quite similar skewness. Hence under the natural graph theory partition of the genetic code there is a preference for more protein sequences to contain fewer runs of amino acids, than they do under the other partitions, meaning that the average run must be longer under the natural partition. This suggests that a corresponding bias may exist in the coding sequences of the actual genes that code for these proteins.