Prevalence of an inherited cancer predisposition syndrome associated with the germ line TP53 R337H mutation in Paraguay.

The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer, and the germline TP53 R337H mutation is the most common mutation reported to date. However, this mutation is associated with a lower cumulative lifetime cancer risk than other mutations in the p53 DNA-binding domain. A detailed statistical analysis of 171,500 DNA tests in Brazilian neonates found that 0.27% of the general population is positive for this mutation, and some of the estimated 200,000 Brazilian R337H carriers in southern and southeastern Brazil have already developed cancer. The present study was designed to estimate R337H prevalence in neighboring Paraguay. To address this question, 10,000 dried blood samples stored in Guthrie cards since 2008 were randomly selected from the Paraguayan municipalities located at the border with Brazil. These samples were tested for R337H mutation using the PCR-restriction fragment length polymorphism assay. This germline mutation was detected in five samples (5/10,000), indicating that the total number of R337H carriers in Paraguay may be as high as 3500. Previous studies have shown that other countries (i.e., Portugal, Spain, and Germany) presented one family with this mutation, leading us to conclude that, besides Brazil and Paraguay, other countries may have multiple families carrying this mutation, which is an inherited syndrome that is difficult to control.

Dissolution properties of calcium phosphate granules with different compositions in simulated body fluid.

Calcium phosphate granules were produced through the calcination of three hydroxyapatites (HAs) at 1150 degrees C: nearly-stoichiometric (NS-HA), calcium-deficient (CD-HA), and carbonated (Carb-HA). The characterization using scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transformed infrared spectroscopy (FT-IR) showed that those granules exhibit strong differences in chemical composition, surface texture, and dissolution behavior. Sample dissolution in a simulated body fluid (SBF) and precipitation of a calcium phosphate layer on the granule surface were followed up for 7 days by chemical analysis of calcium content in SBF. After 80-min reaction, precipitation of new calcium phosphate phases predominates over the dissolution of original granules. Comparison between SEM images and XRD/FT-IR analysis revealed that the composition of the calcium phosphate layer and its precipitation rate depend on the HA composition and its heat treatment. Calcined carbonated apatite induces the precipitation of an octacalcium phosphate (OPC) layer, whereas a carbonated apatite layer is formed from calcined-deficient HA. The calcined nearly-stoichiometric HA exhibits low efficiency in producing carbonated apatite layer.