Combined effects of smoking and alcohol on metabolic syndrome: the LifeLines cohort study.

INTRODUCTION: The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its individual components. METHODS: 64,046 participants aged 18-80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25-30, overweight; BMI≥30 kg/m2, obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis. RESULTS: Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7-71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks. CONCLUSION: Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.

Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer.

PURPOSE: Ovarian cancer patients with intra-tumoral CD3(+) T-lymphocytes in primary tumor tissue have a better prognosis. This study aims to analyze the presence and relative influence of three important T-lymphocyte subsets, tumor-infiltrating CD8(+) cytotoxic T-lymphocytes (CTL), CD45R0(+) memory T-lymphocytes, and FoxP3(+) regulatory T-lymphocytes (Treg), in primary tumor tissue and omental metastases of patients with ovarian cancer. EXPERIMENTAL DESIGN: The number of CD8(+), CD45R0(+), and FoxP3(+) T-lymphocytes was determined by immunohistochemistry on a tissue micro array containing ovarian tumor tissue and/or omental metastases obtained at primary debulking surgery from 306 FIGO stage I-IV ovarian cancer patients. Immunohistochemistry data were correlated to clinicopathological parameters and survival data. RESULTS: High number of CD8(+) CTL and a high CD8(+)/FoxP3(+) ratio in ovarian-derived tumor tissue were associated with increased disease-specific survival and proved to be independent prognostic factors in multivariate analyses. In advanced stage patients, the presence of CD8(+) CTL, CD45R0(+) memory T-lymphocytes, FoxP3(+) Treg or a high CD8(+)/FoxP3(+) ratio in ovarian-derived tumor tissue was associated with an increased disease specific survival in univariate analysis, as was the presence of CD45R0(+) memory T-lymphocytes and FoxP3(+) Treg in omental metastases. Furthermore, in advanced stage patients CD8(+) cytotoxic and FoxP3(+) regulatory T-lymphocytes infiltrating ovarian-derived tumor tissue were independent predictors of increased prognosis. CONCLUSIONS: T-lymphocytes infiltrating primary and metastatic ovarian cancer sites are associated with improved prognosis. These associations are especially distinct in advanced stage patients, underlining the potential for immunotherapy as a broadly applicable therapeutic strategy.

Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings: a feasibility study.

Current morphology-based cervical cancer screening is associated with significant false-positive and false-negative results. Tumor suppressor gene hypermethylation is frequently present in cervical cancer. It is unknown whether a cervical scraping reflects the methylation status of the underlying epithelium, and it is therefore unclear whether quantitative hypermethylation specific PCR (QMSP) on cervical scrapings could be used as a future screening method augmenting the current approach. Cervical scrapings and paired fresh frozen cervical tissue samples were obtained from 53 cervical cancer patients and 45 controls. All scrapings were morphologically scored and analyzed with QMSP for the genes APC, DAPK, MGMT, and GSTP1. To adjust for DNA input, hypermethylation ratios were calculated against DNA levels of a reference gene. Hypermethylation ratios of paired fresh frozen tissue samples and scrapings of cervical cancer patients and controls were strongly related (Spearman correlation coefficient, 0.80 for APC, 0.98 for DAPK, and 0.83 for MGMT; P < 0.001). More cervical cancer patients than controls were DAPK positive (P < 0.001). When cutoff levels for ratios were defined to be above the highest ratio observed in controls, QMSP in cervical scrapings identified 32 (67%) of 48 cervical cancer patients. This feasibility study demonstrates that QMSP on cervical scrapings holds promise as a new diagnostic tool for cervical cancer. The addition of more genes specifically methylated in cervical cancer will further improve the assay.