No association between MDM2 SNP309 promoter polymorphism and basal cell carcinoma of the skin.

BACKGROUND: The MDM2 oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumour suppressor protein. Further, overexpression of the MDM2 gene can inhibit DNA double-strand break repair in a p53-independent manner. Recent studies have shown that a single nucleotide polymorphism (SNP) in the intronic promoter region of MDM2 (called SNP309) can significantly change the expression of MDM2 and thereby suppress the p53 pathway. This SNP was also found to be associated with the onset and risk of different cancer types. Basal cell carcinoma of the skin (BCC) is one of the most common neoplasms in the world. BCC development is associated with environmental factors (especially sun exposure) as well as heritable factors. OBJECTIVES: The present case-control study investigated the association of the MDM2 SNP309 with the risk and the age at onset of BCC. Methods Data from 509 individuals affected by BCC and 513 healthy controls were genotyped with TaqMan polymerase chain reaction. RESULTS: Cases and controls showed a similar genotype distribution and the SNP did not modify the age at onset of BCC. CONCLUSIONS: These results suggest that the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC.

Case-control study in basal cell carcinoma of the skin: single nucleotide polymorphisms in three interleukin promoters pre-analysed in pooled DNA.

BACKGROUND: Basal cell carcinoma (BCC) is one of the most common neoplasms in the world. Development of BCC is associated with environmental factors (especially sun exposure) as well as heritable factors. OBJECTIVES: To analyse three single nucleotide polymorphisms (SNPs) in the promoter regions of interleukin (IL) genes in genomic DNA from 527 cases of BCC and 530 matched controls and to examine if DNA pooling is a useful method on which to base decisions regarding further SNP analysis. METHODS: The SNPs analysed were IL6-597, IL10-1082 and IL1B-511. The SNPs were first analysed from pooled DNA and afterwards from individual samples. The DNA pools resulted from a division of the samples into cases and controls, female and male, and three age groups. In these pools the allele frequencies were estimated by two methods, real-time polymerase chain reaction with allele-specific primers, and quantitative sequencing. RESULTS: No significant association was found when the allele frequencies in cases and controls were compared. However, by analysis of the individual genotypes we found SNP IL6-597 G/A to be significantly associated with BCC risk (P =0.007). Hereby the heterozygous genotype 'GA' had a protective effect (odds ratio 0.64, 95% confidence interval 0.49-0.84). No significant association was found for IL10-1082 and IL1B-511. CONCLUSIONS: The association of SNP IL6-597 with BCC could be found only by individual genotyping, but would have been missed if only data from the pooling analysis had been known.

Childhood respiratory symptoms, hospital admissions, and long-term exposure to airborne particulate matter.

The effects of long-term exposure to air pollution on respiratory symptoms and respiratory hospitalization (for asthma, bronchitis or pneumonia) were assessed in a cross-sectional study of children (ages 7--11 years, N=667) living in a moderately industrialized city in Central Slovakia. Individual health, residence and family history data obtained through the CESAR study were coupled, using Geographic Information System (GIS) technologies, with total suspended particulate (TSP) exposure estimates derived from dispersion modeling of almost all local stationary sources. These data were used to assess, at the intra-city level and child-specific level, the potential for TSP as a risk factor for respiratory disease in children. TSP, PM10, and PM2.5 monitored ambient concentrations are highly correlated in the study location. Modeled TSP concentrations resulting from local source emissions are dominated by a large wood processing facility, suggesting variation in exposures among children. The prevalence of respiratory non-asthmatic symptoms and hospitalizations was associated with increased TSP. No association between long-term exposure to TSP and asthma diagnosis or wheeze symptoms was found. Logistic regression modeling indicated a significant increase in hospital admissions for asthma, bronchitis or pneumonia associated with increasing air pollution (OR 2.16, CI, 1.01--4.60), doctor-diagnosed bronchitis (OR 1.53, CI, 1.02-2.30), and parent-reported chronic phlegm (OR 3.43, CI, 1.64--7.16), expressed as odds for a 15 microg/m3 increase in estimated TSP exposure, and these increases are not due to differences in socio-economic, health care or other identified factors.

Health risk assessment for inhalation exposure to arsenic.

Health risk assessment was used as the formal process to estimate the likelihood and magnitude of the health effects occurring in humans as a result of environmental and occupational exposure to polluting agents. This study was focused at estimating the human health risk of the general and working population living in the region polluted by arsenic for more than 40 years, from combustion of coal with high arsenic content in the power plant. The exposure to arsenic from inhalation was under investigation. A study period of 40 years (1973-1993) was chosen. The study period was defined taking into account, besides the availability of data, the temporal patterns of the technological processes and the trends over time of environmental concentrations. The results from the arsenic risk assessment study were used for the evaluation of the health risk for different population groups in the polluted areas and for different professions of workers exposed to As in a power plant. The results are applicable for the evaluation of risk in real conditions, for health surveillance and for remedial changes and a potential suggestion on technological improvement.

Immune biomarkers in relation to exposure to particulate matter: a cross-sectional survey in 17 cities of Central Europe.

Human population data on air pollution and its effects on the immune system are scarce. A survey was conducted within the framework of the Central European Study of Air Quality and Respiratory Health (CESAR) to measure a panel of immune biomarkers in children of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia. Seventeen cities were chosen to represent a wide range of exposure to outdoor air pollution. In each, ambient particulate matter of less than 10 microns diameter and less than 2.5 microns diameter (PM10 and PM2.5) were measured with a Harvard impactor. Blood was collected from 366 school children aged 9 to 11 yr between 11 April and 10 May 1996. The percentage of B, total T, CD4+, CD8+, and natural killer (NK) lymphocytes was determined by flow cytometry (Becton Dickinson); total immunoglobulins of class G, M, A and E (IgG, IgM, IgA, and IgE) were measured in serum using nephelometry (Behring). Associations between PM and each log-transformed biomarker concentration were studied by linear regression, in a two-stage model. The yearly average concentrations varied from 41 to 96 micrograms/m3 for PM10 across the 17 study areas, from 29 to 67 micrograms/m3 for PM2.5, and from 12 to 38 micrograms/m3 for PM10-2.5 (coarse). Number of B, CD4+, CD8+, and NK lymphocytes increased with increasing concentration of PM, having adjusted for age, gender, parental smoking, laboratory of analysis, and recent respiratory illness. Differences in lymphocyte number were larger and statistically significant for exposure to PM2.5. Similar results were found when we examined the association between PM and lymphocyte number separately for each laboratory. Total IgG was increased with increasing concentration of PM, significantly in the case of PM2.5. When we repeated the analyses with two other statistical approaches the results did not differ from those reported here. The effect of coarse PM on lymphocyte numbers appears small in comparison to PM2.5. One possible interpretation of our findings is that long-term exposure to airborne particulates leads to inflammation of the airways and activation of the cellular and humoral immune system.