ABSTRACT
BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.
Subject(s)
DNA Methylation , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Aged , Biomarkers, Tumor/genetics , Case-Control Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Sputum/chemistryABSTRACT
BACKGROUND: Lifestyle changes over the last 30 years are the most likely explanation for the increase in allergic disease over this period. AIM: This study tests the hypothesis that the consumption of fast food is related to the prevalence of asthma and allergy. METHODS: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) a cross-sectional prevalence study of 1321 children (mean age = 11.4 years, range: 10.1-12.5) was conducted in Hastings, New Zealand. Using standard questions we collected data on the prevalence of asthma and asthma symptoms, as well as food frequency data. Skin prick tests were performed to common environmental allergens and exercise-induced bronchial hyperresponsiveness (BHR) was assessed according to a standard protocol. Body mass index (BMI) was calculated as weight/height2 (kg/m2) and classified into overweight and obese according to a standard international definition. RESULTS: After adjusting for lifestyle factors, including other diet and BMI variables, compared with children who never ate hamburgers, we found an independent risk of hamburger consumption on having a history of wheeze [consumption less than once a week (OR = 1.44, 95% CI: 1.06-1.96) and 1+ times a week (OR = 1.65, 95% CI: 1.07-2.52)] and on current wheeze [consumption less than once a week (OR = 1.17, 95% CI: 0.80-1.70) and 1+ times a week (OR = 1.81, 95% CI: 1.10-2.98)]. Takeaway consumption 1+ times a week was marginally significantly related to BHR (OR = 2.41, 95% CI: 0.99-5.91). There was no effect on atopy. CONCLUSIONS: Frequent consumption of hamburgers showed a dose-dependent association with asthma symptoms, and frequent takeaway consumption showed a similar association with BHR.
Subject(s)
Asthma/epidemiology , Asthma/etiology , Beverages/adverse effects , Diet/adverse effects , Meat Products/adverse effects , Adult , Animals , Bronchial Hyperreactivity/epidemiology , Bronchial Hyperreactivity/etiology , Cattle , Child , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Respiratory Sounds/etiology , Risk Factors , Skin TestsABSTRACT
BACKGROUND: There has been a concurrent increase in the prevalence of obesity and asthma in recent years in New Zealand and other countries. METHODS: Two cross sectional surveys performed in 1989 and 2000 were used to test this association in children of mean age 11.7 years. Body mass index (BMI) was calculated as weight/height2 (kg/m2) and obesity and overweight defined according to an international standard. Standard questions were used to measure the prevalence of asthma symptoms. RESULTS: Significant increases in the prevalence of reported symptoms and disease between 1989 and 2000 were not explained by a concurrent increase in the prevalence of obesity. In 2000, multivariate analysis showed that increasing BMI standard deviation score was significantly associated with current wheeze (p=0.002), inhaled steroid use (p=0.004), and the use of any medication (p=0.001). None of the associations was significantly different for boys or girls. CONCLUSION: There is some evidence for an association of obesity with asthma symptoms and treatment but this does not explain the increasing prevalence of this disease.
