Methods for the analysis of histone H3 and H4 acetylation in blood

LBH589 is one of the many histone deacetylase inhibitors (HDACi) that are currently in clinical trial. Despite their wide-spread use, there is little literature available describing the typical levels of histone acetylation in untreated peripheral blood, the treatment and storage of samples to retain optimal measurement of histone acetylation nor methods by which histone acetylation analysis may be monitored and measured during the course of a patient’s treatment. In this study, we have used cord or peripheral blood as a source of human leukocytes, performed a comparative analysis of sample processing methods and developed a flow cytometric method suitable for monitoring histone acetylation in isolated lymphocytes and liquid tumors. Western blotting and immunohistochemistry techniques have also been addressed. We have tested these methods on blood samples collected from four patients treated with LBH589 as part of an Australian Children’s Cancer Clinical Trial (CLBH589AAU03T) and show comparable results when comparing in vitro and in vivo data. This paper does not seek to correlate histone acetylation levels in peripheral blood with clinical outcome but describes methods of analysis that will be of interest to clinicians and scientists monitoring the effects of HDACi on histone acetylation in blood samples in clinical trials or in related research studies

The association between secondhand smoke and the risk of developing acute coronary syndromes, among non-smokers, under the presence of several cardiovascular risk factors: The CARDIO2000 case-control study

BACKGROUND: The purpose of this study was to investigate the association between secondhand smoke and the risk of developing a first event of acute coronary syndromes (ACS), i.e. acute myocardial infarction or unstable angina, among non-smokers, in relation to the presence of several other cardiovascular risk factors. METHODS: Eight hundred and forty-eight patients with first event of ACS and 1078 cardiovascular disease-free matched controls completed a detailed questionnaire regarding their exposure to secondhand smoke, among other investigated parameters. RESULTS: Two hundred and ninety–seven (35%) of the patients and 259 (24%) of the controls were defined as secondhand smokers. After controlling for several potential confounders, the results showed that non-smokers occasionally (< 3 time per week) exposed to cigarette smoke were associated with 26% higher risk of ACS (OR = 1.26, P-value < 0.01) compared to non-smokers not exposed to smoke, while regular exposure is associated with 99% higher risk of developing ACS (OR = 1.99, P-value < 0.001). Moreover, the previous risk increases progressively from 15% to 256% if one or more of the classical cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes mellitus, sedentary life and family history of premature coronary heart disease) are present. CONCLUSIONS: Consequently, this study supports the hypothesis that even occasional secondhand smoke increases the risk of developing acute coronary syndromes, especially when other risk factors are present. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease are important

Alcoholic beverages and risk of renal cell cancer

Using a mailed questionnaire, we investigated the risk of renal cell cancer in relation to different types of alcoholic beverages, and to total ethanol in a large population-based case–control study among Swedish adults, including 855 cases and 1204 controls. Compared to non-drinkers, a total ethanol intake of >620 g month−1 was significantly related to a decreased risk of renal cell cancer (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4–0.9; P-value for trend=0.03). The risk decreased 30–40% with drinking more than two glasses per week of red wine (OR 0.6, 95% CI 0.4–0.9), white wine (OR 0.7, 95% CI 0.4–1.0), or strong beer (OR 0.6, 95% CI 0.4–1.0); there was a clear linear trend of decreasing risk with increasing consumption of these beverages (P-values for trends <0.05)

Occupational, domestic and environmental mesothelioma risks in the British population: a case–control study

We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8–96.8) for carpenters (LR 1 in 17), 17.1 (10.3–28.3) for plumbers, electricians and painters, 7.0 (3.2–15.2) for other construction workers, 15.3 (9.0–26.2) for other recognised high-risk occupations and 5.2 (3.1–8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (∼1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3–3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture

Risk of cancers of the lung, head and neck in patients hospitalized for alcoholism in Sweden

Alcoholic patients are at increased risk of cancers of the head and neck but little information is available on the magnitude of the risk for specific sites and for different histological types. We followed 182 667 patients with a hospital discharge diagnosis of alcoholism during 1965–1994, for an average of 10.2 years. We compared their incidence of site- and histological type-specific cancers of the oral cavity, pharynx, larynx and lung with that of the national population. The standardized incidence ratio (SIR) of cancer of the oral cavity and pharynx was 5.33 (95% confidence interval [CI] 5.04–5.64, based on 1207 cases). The SIRs of laryngeal and lung cancer were 4.21 (95% Cl 3.78–4.68, 347 cases) and 2.40 (2.29–2.51, 1880 cases), respectively. The SIR was highest for cancers of the hypopharynx, floor of the mouth, mesopharynx and base of the tongue. The relative excess of lung cancer was similar for squamous cell carcinoma and adenocarcinoma. Low age at first hospitalization was associated with higher SIRs for all sites under study. 25 years after first hospitalization for alcoholism, the cumulative probability of developing a lung cancer was in the order of 5%, for oral and pharyngeal cancer it was 2.5%, and for oesophageal or laryngeal cancer 1% each. Our study shows that the risk of head and neck cancer among heavy drinkers is highest for sites in direct contact with alcohol. The high risk of head and neck neoplasms may justify specific medical attention. © 2001 Cancer Research Campaign http://www.bjcancer.co

Use of NSAIDs, smoking and lung cancer risk

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders. Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses. After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 0.86 (95% confidence intervals, 0.65–1.14) for lung cancer associated with any use of NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of dispensed prescriptions per year during the 1–3 years before the index date with a relative risk of 0.49 (0.28–0.84) among those with four or more prescriptions per year during this period. Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer

Case-control study on uveal melanoma (RIFA): rational and design

BACKGROUND: Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. METHODS/DESIGN: We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding

Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area

Abstract Background To examine the influence of cigarette, cigar and pipe smoking, cessation of cigarette smoking and passive smoke exposure on the risk of pancreatic cancer. Methods Exposure data were collected during in-person interviews in a population-based case-control study of pancreatic cancer (N = 532 cases, N = 1701 controls) in the San Francisco Bay Area. Odds ratios (ORs) were adjusted for potential confounders. Results The adjusted odds ratio (OR) of pancreatic cancer among current smokers was 1.9 (95% confidence interval (CI), 1.4-2.7). A significant, positive trend in risk with increasing pack-years of smoking was observed (P-trend &lt;0.0001). Compared with participants who continued to smoke, former smokers had no statistically significant elevation in risk of pancreatic cancer 10 years after smoking cessation, with risk reduced to that of never smokers regardless of prior smoking intensity. Both men and women experienced similar increased risk of pancreatic cancer with increasing smoking duration. Cigar and pipe smoking and exposure to passive smoke were not associated with pancreatic cancer. Conclusions Cigarette smoking is associated with an increased risk of pancreatic cancer. Smokers who had quit for ≥10 years no longer experienced an increased risk. Future work will help to determine the effect of declining smoking rates on pancreatic cancer incidence

Systematic review of the epidemiological evidence comparing lung cancer risk in smokers of mentholated and unmentholated cigarettes

<p>Abstract</p> <p>Background</p> <p>US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic.</p> <p>Methods</p> <p>Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted.</p> <p>Results</p> <p>Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use.</p> <p>The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8), with no increase in males (1.01, 0.84-1.22, n = 5), females (0.80, 0.67-0.95, n = 5), White people (0.87, 0.75-1.03, n = 4) or Black people (0.90, 0.73-1.10, n = 4). Estimates for current and ever smokers are similar. The combined estimate for long-term use (0.95, 0.80-1.13, n = 4) again suggests no effect of mentholation.</p> <p>Conclusion</p> <p>Higher lung cancer rates in Black males cannot be due to their greater preference for mentholated cigarettes. While some study weaknesses exist, the epidemiological evidence is consistent with mentholation having no effect on the lung carcinogenicity of cigarettes.</p