Mutagenicity of smoke condensates from cigarettes, cigars and pipe tobacco.

Smoke condensates from cigarettes, cigars and pipe tobacco were mutagenic on Salmonella typhimurium TA100 and TA98 when activated with rat liver microsomal system. Mutagenicity of a unit weight of smoke condensate was rather high in cigars, low in pipe tobacco and intermediate in cigarettes. Specific mutagenic activity was almost comparable among smoke condensates from low- to high-tar cigarettes, although some variations were observed depending upon the country producing the cigarettes. Marked mutagenicity of cigarette smoke condensate could not be explained by the benzo (a) pyrene or nitroso compounds it actually contained, suggesting the presence of other very potent mutagens in tobacco smoke condensates.     

Urinary excretion of mutagens in smokers of cigarettes with various tar and nicotine yields, black tobacco, and cigars

Frameshift mutagens were isolated and concentrated from smokers' urine employing a method recently described. Urine concentrates of the habitual smokers and non-smokers who smoked cigarettes with low-, medium-, and high tar/nicotine yields, RCN (Reduced Condensate and Nicotine; artificial cigarettes containing cotobacco materials), black tobacco, and cigars were tested for mutagenicity in the Salmonella/mammalian microsome assay using Salmonella typhimurium TA98. Non-smokers who smoked 5 and habitual smokers who smoked 10 cigarettes of various tar and nicotine yields excreted more mutagens in urine with low-tar cigarettes than with medium- or high-tar cigarettes. Consuming more than 10 cigarettes a day resulted in a higher urinary excretion of mutagens with medium-tar cigarettes than with high-tar cigarettes. Smoking 5 RCN cigarettes a day by habitual smokers resulted in a higher urinary excretion of mutagens than smoking 5 commercial brand of cigarettes. In contrast, smoking 10 RCN cigarettes resulted in a lower urinary excretion of mutagens than smoking 10 commercial brand of cigarettes. The highest mutagenic activity was found with the urine of a habitual black tobacco smoker. Smoking cigars by non-smokers resulted in a very weak mutagenic activity of urine.     

Cigar and pipe smoking,smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)

BackgroundCigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco.Materials and methodsWe conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case–control studies (6056 cases and 11 338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates.ResultsCompared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2–2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4–1.6). The OR was 1.1 (95% CI 0.69–1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75–1.3).ConclusionThis collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.     

Water pipe (shisha) smoking and associated factors among Malaysian university students

Objective: The objective of this study was to determine the prevalence of waterpipe (shisha) smoking and associated factors among Malaysian university students. Methodology: A total of 200 university students from Management and Science University participated in this study. The survey was conducted by simple random sampling by randomly distributing self-administered questionnaires to the library, cafeterias and classes. The protocol of this study was approved by the ethics committee of Management and Science University. Consent forms were obtained from the students before they answered the questionnaire. Statistical analyses were performed using the Statistical Package for Social Science (SPSS) version 13. with the Student’s t-test for comparison of the mean practice and backward multiple linear regression for multivariate analysis. Results: The majority of the subjects were male, single, Malay and from urban areas (61.5%, 94.5%, 66%, 76.5%; respectively). In this study 30% of the study participants were shisha smokers. Regarding knowledge about shisha smoking, the majority (48.5%) mentioned that shisha is less harmful than cigarettes and 55% reported that shisha is less addictive. Univariate analysis showed that age, race, sex and income significantly influenced the practice of smoking shisha among university students (p=0.019, p=0.002, p=0.001, p=0.018; respectively). For multivariate analysis, income and gender demonstated significant influence (both p=0.001). Conclusion: There was a high prevalence of shisha smoking among Malaysian university students and knowledge about the dangers is low. Income and gender significantly influenced the practice of smoking shisha in our population. Banning of smoking including shisha smoking in public places is strongly recommended.     

Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.     

Factors modifying exposure to environmental tobacco smoke in children (Athens, Greece)

The aim of the study was to investigate individual, family, and environmental factors which may modify exposure of children to environmental tobacco smoke (ETS). A total of 2,108 children of both genders, aged up to 14 years old, were enrolled in the study. Parents of the children provided information concerning several factors that may affect exposure to ETS. Cotinine-to-creatinine ratios in spot urine samples were measured for each child. These values were logtransformed and regressed on a series of exposure variables. Among children, 73 percent were exposed to ETS generated by at least one smoker in the household. Exposure to ETS was affected by the following factors: cigarettes smoked by parents while the child was at home (increase by 37 percent per 10 cigarettes daily, 95 percent confidence interval [CI]=32-43 percent); precautions taken by parents (no cf yes, increase by 38 percent, CI=24-54 percent); child's age (decrease by nine percent per year, CI=-11--8 percent); gender (male lower than female by 13 percent, CI=-21--3 percent); day of the week (Monday cf Tuesday-through-Sunday, increase by 28 percent, CI=14-44 percent); floor surface area (decrease by nine percent per 20m2, CI=-14--5 percent); heating (central cf non-central decrease by 14 percent, CI=-25--2 percent); maternal education (decrease by nine percent per five years, CI=-18-0 percent); paternal education (decrease by seven percent per five years, CI=-15-2 percent). It is concluded that several household-related factors affect exposure to ETS and that this exposure can be reduced by about one-third by simple precautions taken by smoking parents.     

Effects of tobacco smoking on cancer and cardiovascular disease in urban black South Africans

Demographic and lifestyle information from 9690 black patients diagnosed with cancer or cardiovascular disease was collected in an ongoing case-control study in Johannesburg, South Africa. Compared to never smokers, the odds ratio (OR) for lung cancer among current smokers was 16.3 (95% confidence interval (CI), 9.6-27.6) for men and 6.4 (95% CI, 4.0-10.4) for women. The corresponding OR for other smoking-related cancers was 4.6 (95% CI, 3.7-5.7) among men and 1.9 (95% CI, 1.6-2.2) among women, and for cardiovascular disease, 3.4 (95% CI, 2.1-5.4) among men and 1.5 (95% CI, 1.1-2.1) among women. Risks were higher among smokers than former smokers, and all risk estimates increased with increasing levels of smoking duration and intensity. Non-electric domestic fuel was associated with approximately 60% increase in the risk of smoking-related cancer, but not cardiovascular disease. Risks for cancers of cervix, oesophagus, oral cavity/pharynx, stomach, larynx, pancreas and anogenital region, as well as squamous cell carcinoma of skin were all significantly higher among current than never-smokers, with ORs ranging from 1.5 for cervix (95% CI, 1.2-1.8) to 14.7 for larynx (95% CI, 7.2-30). The risks of tobacco-related disease reported here are similar to that currently observed in Western countries, even though cigarette consumption is relatively low in this population.     

A prospective study on active and environmental tobacco smoking and bladder cancer risk (The Netherlands)

Objective: In a prospective cohort study among 120,852 adult subjects the authors investigated the associations between cigarette, cigar, pipe, environmental tobacco smoking (ETS), and bladder cancer. Methods: In 1986 all subjects completed a questionnaire on cancer risk factors. Follow-up for incident bladder cancer was established by linkage to cancer registries until 1992. The case–cohort analysis was based on 619 cases and 3346 subcohort members. Results: Compared with lifelong non-smokers the age- and sex-adjusted incidence rate ratios (RR) for ex- and current cigarette smokers were 2.1 (95% CI 1.5–3.0) and 3.3 (95% CI 2.4–4.6), respectively. The RR for smoking duration was 1.03 (95% CI: 1.02–1.04) per 1-year increment. The RR per 10 cigarettes/day was 1.3 (95% CI 1.2–1.4). Tar and nicotine exposure increased bladder cancer risk only weakly. It appeared that associations of cigarette smoking characteristics with bladder cancer risk were largely attributable to cigarette smoking duration only. Smoking cessation, age at first exposure, filter-tip usage, cigar and pipe smoking, and ETS were no longer associated with bladder cancer risk after adjustment for frequency and duration of smoking. Conclusions: The authors conclude that current cigarette smokers have a three-fold higher bladder cancer risk than non-smokers. Ex-smokers experience a two-fold increased risk. About half of male bladder cancer and one-fifth of female bladder cancer was attributable to cigarette smoking. Other smoking types (cigar, pipe, or ETS) were not associated with increased risks.     

Differential toxicity and clearance kinetics of chromium(III) or (VI) in mice

The acute and subacute toxicities of several chromium(III) andchromium(VI) compounds were determined in NZC and (CxO) miceinjected i.p. The distal median lethal doses (more than 10 daysafter treatment) averaged (17.9 ± 1.8) x 10^–6 gchromium/g body weight regardless of the oxidation state ofthe chromium compound injected (chromium(III) sulphate may bean exception), but acute toxicity (3 days) was much greaterwith chromium(VI) compounds. Acid digests of entire male micethat were administered i.p. one-sixth of the distal LD₅₀, eitheronce or repeatedly at weekly intervals, were analysed to determinethe whole body persistence and clearance kinetics of chromium.Mice dosed once with chromium(III) retained 6.5 times more chromiumat 21 days than mice treated with chromium(VI). When chromium(III)was given at weeky intervals mice accumulated 6 times more chromiumby 8 weeks than chromium(VI)-treated mice, though only the lattershowed symptoms of chronic toxicity. Whole body chromium concentationscontinued to rise with further chromium(III) treatments, butslowly declined with chromium(VI). Analyses of fecal and urinaryexcretion confirmed most of the urinary chromium clearance occurredsoon after injection, and that chromium excretion from chromium(VI)-treatedanimals was much faster in both urine and feces than from micegiven chromium(III). The differential storage and clearancekinetics of chromium(III) and chromium(VI) compounds may besignificant in experimental chromium carcinogenesis studiesand in the toxicology of chromium in workers exposed industriallyto potentially carcinogenic chromium-containing dusts or aerosols.     

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

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.     

A European validation study of smoking and environmental tobacco smoke exposure in nonsmoking lung cancer cases and controls

Objectives: The purpose of this study was to validate, in a case-control study, the reporting by lung cancer cases and controls of their own lifetime smoking habits and of the smoking habit of the spouse. Methods: In a multicenter (Sweden, Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung cancer, subjects were screened by repeated probing to exclude regular smokers of one cigarette/day or more for one year or more, and to quantify any occasional smoking. We then performed a short validation interview with next-of-kin in three centers. Results: Only five of 408 index subjects who had never smoked regularly (1.7 percent) were reported by next-of-kin to be former regular smokers. These subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack years. Among 351 subjects with quantitative smoking information from both sources who reported ever smoking 400 cigarettes or less (the definition of never-smoker used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more than this amount occasionally according to next-of-kin. Misclassification was not higher for cases than controls. Relative risks for lung cancer associated with indicators of ETS exposure were not substantially altered by excluding the nine possibly misclassified subjects. The reports from 223 pairs of index subjects and next-of kin regarding the cumulative amount smoked by the spouse agreed quite well (Spearman's rank correlation 0.75 for reported smokers, 0.92 for all subjects). Only one index subject failed to report a spouse who had smoked regularly (99 percent sensitivity). Conclusions: Smoking status and exposure to spousal ETS as reported by lung cancer cases and controls agreed strongly with reports by next-of-kin. Overall, our results suggest that bias from smoker misclassification is likely to be insignificant, and they contribute to the evidence linking exposure to ETS with an increased risk of lung cancer.     

Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States)

Objective: A population-based case–control study was conducted to examine the hypothesis that active and passive tobacco smoking were associated with the risk of epithelial ovarian cancer. Methods: In-person interviews were obtained from 558 women with epithelial ovarian cancer (431 invasive, 127 borderline) and 607 population controls regarding active lifetime tobacco smoking, environmental tobacco smoke exposure in utero and during childhood, and other factors that may be related to the development of ovarian cancer. Results: No significant associations of ever or former tobacco smoking with the risk of invasive or borderline ovarian cancer were found, although long-term ex-smokers of 20 years or more were at significantly reduced risk of invasive cancer. Significant, positive dose–response relations of the number of cigarettes smoked per day and pack-years with the odds ratios for borderline cancer were evident. No association of active tobacco smoking with risk was found by histologic subtype of invasive ovarian cancer. Smokers were at significantly increased risk for borderline serous cystadenoma (OR: 1.91; 95% confidence intervals, CI: 1.09–3.34), but not for borderline mucinous cystadenoma. When we limited the analyses to current smokers, age-started smoking was significantly inversely related to the risk of invasive, but not borderline ovarian cancer. We found no association of gestational or childhood environmental tobacco smoke exposure with the risk of invasive or borderline ovarian cancer among never smokers. Conclusions: These findings do not support an association of active tobacco smoking with the risk of invasive ovarian cancer. An increased risk of borderline serous cystadenoma among smokers must be viewed with caution.     

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking.

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.