Obesity impacts on many issues of pulmonary medicine, where it is debated if obesity is linked to asthma, atopy or altered lung function tests. Our study aimed to investigate primarily the effect of obesity on the lung function tests and secondary the possible link of obesity with atopy and asthma in a large cohort of children in Greece. Body mass index (BMI) and data from a questionnaire for lung health, atopy, nutritional habits and family history were obtained from 2,715 children aged 6-11 years. Six hundred fifty-seven children with BMI>85th percentile (357 overweight, 300 obese) and a group of 196 normal weight children underwent spirometry. The % expected FVC, FEV(1), FEF(25-75), and FEV1/FVC were significantly reduced in overweight or obese children compared to children with normal weight (P = 0.007, P < 0.001, P < 0.001, and P < 0.001, respectively). Reported atopy was significantly higher in overweight or obese children compared to normal weight children (P = 0.008). High BMI remained a strong independent risk factor for asthma (OR = 2.17, 95% CI = 1.22-3.87, P = 0.009) and for atopy (OR = 2.06, 95% CI = 1.32-3.22, P = 0.002). The effect of increased BMI on asthma was significant in girls, but not in boys (OR = 2.73, 95% CI = 1.09-6.85, P = 0.032; OR = 1.74, 95% CI = 0.83-3.73, P = 0.137, respectively). In conclusion we have shown that high BMI remains an important determinant of reduced spirometric parameters, a risk factor for atopy in both genders and for asthma in girls.

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BackgroundPhosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study, we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma.MethodsNinety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2–57 months, median 24 months).ResultsSixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% confidence interval [CI]: 28.5–35.8 months; median 30.0 months); 1-, 2- and 3-year survival rates were 86.5% ± 3.5%, 57.3% ± 5.1%, and 37.1% ± 5.4%, respectively. Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression (35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression, P = 0.009; hazard ratio [HR] 1.95, 95% CI: 1.15–3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival (HR 2.15, 95% CI: 1.22–3.79, P = 0.026). A combined p53/γ-H2AX analysis was performed, and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes.ConclusionOur study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer. Further studies are needed to confirm our results.

Abstract. DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli (APC) and Ras association domain family 1 isoform A (RASSF1A) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P= 0.012), higher stage (P= 0.014) and methylated RASSF1A status (P= 0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, P<0.001) and advanced disease (37±7 vs. 15±3 months, P<0.001), compared with patients with methylated APC. Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, P<0.001) and advanced disease (28±4 vs. 16±3 months, P<0.001) than patients with methylated RASSF1A. The observed significant correlations between APC and RASSF1A promoter methylation status and survival may be indicative of a prognostic role for these genes in CRC, which requires additional testing in larger studies.