Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans

PurposeDisparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.MethodsTo test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95% confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.ResultsA nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p=0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p=0.015 and p=0.018, respectively).ConclusionsOur results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs. Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-014-0361-y) contains supplementary material, which is available to authorized users

Incentivi fiscali agli investimentiin R&S: una proposta per l'Italia

The low level of business expenditure in R&D (BERD) in Italy – its ratio to GDP was less than 0.6% in 2004, well below the EU average – urges the adoption of fiscal incentives to R&D, as suggested by the European Commission, in order to achieve the EU objectives set in Barcelona (2002): 3% of total R&D expenditures to GDP by the year 2010 (2/3 from the business sector). This paper presents an analysis of the main reasons and characteristics of the tax incentives to BERD and a proposal for Italy. A permanent tax credit on total BERD is proposed and its effects are analysed under alternative scenarios. Estimates show that a permanent tax credit between 15% and 52% of total BERD should foster R&D business expenditure by generating an annual growth ranging from 5% to 15%, letting the BERD to GDP ratio to rise to a maximum of 1.3% within 5 years

Costi e benefici del distacco da una giurisdizione locale: il caso di una provincia

The proper size of local jurisdictions is one of the problems the economic theory of fiscal federalism deals with. On theoretical grounds, the economic literature identifies the benefits and costs of larger vs. smaller jurisdictions mainly in economies of scale and differences in population preferences, respectively. Gains and losses due to the tax-transfer mechanism are often also considered. In practice, any decentralised country may face the two opposite phenomena of small jurisdictions merging to found a larger one and/or the communities belonging to a single political-administrative unit separating so as to give rise to two (or more) smaller jurisdictions. In this paper the latter case is analysed with special reference to the possible splitting of the Italian province of Reggio Calabria and the founding of a new province in its eastern part. The mentioned approaches are jointly used so as to provide a unitary cost-benefit evaluation. Firstly, the efficiency gains and losses from the province splitting are considered. By using indicators of the population income, wealth and consumption, of demographic and education composition and of political opinions, the gains in preference homogeneity are tested also through the cluster methodology and a spatial analysis. Then the economies of scale are analysed with respect to the administrative offices, and the additional political and bureaucratic costs are inferred using data from the mother-province budget. Finally, an analysis of financial sustainability of the new province is accomplished, through a simulation of its budget and the calculation of fiscal and financial indicators. While no gains in terms of better correspondence of the new province decisions to local preferences may be hypothesized as a consequence of the separation from the old province, higher costs due to the doubling of political and administrative apparatus and a worsening of fiscal and financial situations should be expected. The well known result that the secession from large jurisdictions comes out in net losses for poorer areas appears to be confirmed

Human colonocytes in primary culture: a model to study epithelial growth, metabolism and differentiation.

The purpose of this work was to set up an in vitro model for the study of normal and pathological functions of the colonic epithelium. We have isolated colonic crypts by mild proteolytic digestion and mechanical dissociation of human biopsy material obtained during colonoscopy. The crypts, free of connective tissue, when placed in culture rapidly attached to the substrate and formed colonies containing over 95% of epithelial cells. Histochemical and ultrastructural characterization of the colonies showed the presence of both absorptive and secretory cells, exhibiting a high degree of differentiation. Proliferative activity occurred mostly during the first 24 h and progressively declined thereafter. The cells survived and maintained differentiated characteristics for at least three days in culture. This method can be used to study normal functions of the colonic epithelium. It may also be employed to investigate both noxious and protective factors in pathological conditions such as inflammatory bowel disease and colorectal neoplasia

BioMed Research International / Quantitative Image Analysis of Epithelial and Stromal Area in Histological Sections of Colorectal Cancer : An Emerging Diagnostic Tool

In colorectal cancer (CRC), an increase in the stromal (S) area with the reduction of the epithelial (E) parts has been suggested as an indication of tumor progression. Therefore, an automated image method capable of discriminating E and S areas would allow an improved diagnosis. Immunofluorescence staining was performed on paraffin-embedded sections from colorectal tumors (16 samples from patients with liver metastasis and 18 without). Noncancerous tumor adjacent mucosa () and normal mucosa () were taken as controls. Epithelial cells were identified by an anti-keratin 8 (K8) antibody. Large tissue areas (563mm2/slide) including tumor center, tumor front, and adjacent mucosa were scanned using an automated microscopy system (TissueFAXS). With our newly developed algorithms, we showed that there is more K8-immunoreactive E in the tumor center than in tumor adjacent and normal mucosa. Comparing patients with and without metastasis, the E/S ratio decreased by 20% in the tumor center and by 40% at tumor front in metastatic samples. The reduction of E might be due to a more aggressive phenotype in metastasis patients. The novel software allowed a detailed morphometric analysis of cancer tissue compartments as tools for objective quantitative measurements, reduced analysis time, and increased reproducibility of the data.(VLID)489640