Bladder cancer, prostate cancer, and kidney cancer, due to their high morbidity and mortality rates, result in significant economic and health care costs. Arsenic exposure affects the drinking water of millions of people worldwide. Long-term exposure to arsenic, even in low concentrations, increases the risk of developing various cancers. Smoking is also one of the leading causes of bladder, prostate and kidney cancers. Accordingly, this research reviews the relationship between arsenic exposure and smoking with three kinds of urinary tract cancers (bladder cancer, prostate cancer, and kidney cancer) due to their widespread concern for their negative impact on public health globally. In this review, we have gathered the most current information from scientific databases [PubMed, Scopus, Google Scholar, ISI web of science] regarding the relationship between arsenic exposure and tobacco smoking with the risk of bladder, prostate, and kidney cancer. In several studies, a significant relationship was determined between the incidence and mortality rate of the above-mentioned cancers in humans with arsenic exposure and tobacco smoking. The decrease or cessation of smoking and consumption of arsenic-free water significantly declined the incidence of bladder, prostate, and kidney cancers.

Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide. Within Western countries, obesity has been associated with an increase in esophageal AC. A striking report from the World Health Organization (WHO) stated that worldwide obesity has tripled since 1975. In 2016, the WHO reported that greater than 1.9 billion adults are overweight and over 650 million were obese. In this review our goal is to analyze the esophageal cancer trends of China, which is the largest contributor among the esophageal cancer "Asian belt." Our intent is to evaluate whether there is a correlation between the rise in esophageal adenocarcinoma and obesity in this esophageal cancer "hotspot." With further analysis, the high-risk populations that are identified can be targeted to implement preventative strategies. This focus will aid in decreasing the burden of esophageal cancer at the global health level by addressing preventative strategies, such as screening endoscopy and lifestyle modifications. For example, WHO developed a global action plan on physical activity in response to the rise in obesity worldwide. Prevention is key to decreasing the rate of esophageal adenocarcinoma as majority of cases are diagnosed in the late stages leading to high mortality rates.

Introduction: Use of non-cigarette tobacco products such as cigars and pipe has been increasing, even though these products entail exposure to similar carcinogens to those in cigarettes. More research is needed to explore the risk of these products to guide cancer prevention efforts.Methods: To measure the association between cigars and/or pipe smoking, and cancer incidence in men, we performed meta-analyses of data from five prospective cohorts. Cox regression was used to evaluate the association between different aspects of cigars and pipe smoking and risk of each smoking-related cancer (head and neck, esophagus, lung, stomach, liver, pancreas, kidney, and bladder) for each study. Adjusted HRs were combined using random-effects models.Results: Cigars and/or pipe smokers were at increased risk for head and neck [HR, 1.51; 95% confidence interval (CI), 1.22-1.87], lung (HR, 2.04; 95% CI, 1.68-2.47), and liver cancers (HR, 1.56; 95% CI, 1.08-2.26). Ever-smokers of cigars and/or pipe had an increased risk of developing a smoking-related cancer when compared with never smokers of any tobacco product (overall HR, 1.07; 95% CI, 1.03-1.12). The risk for smoking-related cancers was also increased in mixed smokers who smoked cigars or pipe as well as cigarettes, even when they were smoking predominantly pipe or cigars.Discussion: This pooled analysis highlights the increased risk for smoking-related cancers, particularly for lung and head and neck cancers in exclusive and predominant smokers (former and current) of cigars and pipe. Tobacco prevention efforts should include these products in addition to cigarettes. Cancer Prev Res; 10(12); 704-9. ©2017 AACR.

Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole.

Cigarette smoking is known to cause a wide range of damaging health outcomes; however, the effects of non-cigarette tobacco products are either unknown or perceived as less harmful than cigarettes. Smokeless tobacco, cigar smoking, and waterpipe smoking have increased in usage over the past few decades. Some experts believe that their use is reaching epidemic proportions. Factors such as a perception of harm reduction, targeted advertising, and unrecognized addiction may drive the increased consumption of non-cigarette tobacco products. In particular, the need for social acceptance, enjoyment of communal smoking activities, and exotic nature of waterpipe smoking fuels, in part, its popularity. The public is looking for "safer" alternatives to smoking cigarettes, and some groups advertise products such as smokeless tobacco and electronic cigarettes as the alternatives they seek. Though it is clear that cigar and waterpipe tobacco smoking are probably as dangerous to health as cigarette smoking, there is an opinion among users that the health risks are less compared to cigarette smoking. This is particularly true in younger age groups. In the cases of smokeless tobacco and electronic cigarettes, the risks to health are less clear and there may be evidence of a harm reduction compared to cigarettes. In this article, we discuss commonly used forms of non-cigarette tobacco products, their impacts on lung health, and relevant controversies surrounding their use.

Net survival is a key measure in cancer control, but estimates for cancers that are strongly associated with smoking may be biased. General population life tables represent background mortality in net survival, but may not adequately reflect the higher mortality experienced by smokers.

Life tables adjusted for smoking were developed, and their impact on net survival and inequalities in net survival for laryngeal and lung cancers was examined.

The 5-year net survival estimated with smoking-adjusted life tables was consistently higher than the survival estimated with unadjusted life tables: 7% higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using smoking-adjusted life tables was more pronounced in affluent patients; the deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from 11% to 14%.

Using smoking-adjusted life tables to estimate net survival has only a small impact on the deprivation gap in survival, even when inequalities are substantial. Adjusting for the higher, smoking-related background mortality did increase the estimates of net survival for all deprivation groups, and may be more important when measuring the public health impact of differences or changes in survival, such as avoidable deaths or crude probabilities of death.

Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case-control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

To investigate an effect of smoking cessation on chronic obstructive pulmonary disease (COPD) mortality in Asians.

The data was obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 41465 Japanese men and 52662 Japanese women aged 40-79 years who had no history of COPD, asthma, other chronic lung diseases, cardiovascular disease or cancer were followed between 1988 and 2008.

During median 18-year of follow-up, there were 285 (251 men and 34 women) documented deaths from COPD. Multivariable-adjusted hazard ratios with 95% confidence intervals of COPD death were 4.46 (2.72-7.29) and 9.26 (4.19-20.5), respectively for current male and female smokers when compared to never smokers. Compared with current smokers, the multivariable HRs for 5-9 years and 10 years or more smoking cessation prior to baseline were 0.44 (0.22-0.87) and 0.36 (0.22-0.58) in men, respectively while the HR for never smokers was 0.30 (0.16-0.57). There were an insufficient number of COPD deaths in women to clarify this association.

Smoking cessation for ten years or more prior to enrollment reverses the excess risk of COPD mortality to a level similar to that observed among never smokers in men.

Nicotine may contribute to accelerated atherogenesis by inducing hyperlipidemia, injuring endothelial cells, and/or promoting thrombosis, although the evidence is not conclusive. Nicotine is likely to contribute to acute ischemic events in people who already have coronary heart disease via adverse effects on systemic hemodynamics, by promoting thrombosis, constricting coronary arteries, and/or facilitating arrhythmogenesis. Pharmacodynamic studies suggest that nicotine inhaled in cigarette smoke may have different cardiovascular effects than that absorbed more slowly, as from nicotine gum or transdermally. The safety of chronic nicotine exposure, such as with medicinal use of nicotine, cannot be predicted and requires empiric evaluation.

Smoking is a known lung cancer cause, but no detailed quantitative systematic review exists. We summarize evidence for various indices.

Papers published before 2000 describing epidemiological studies involving 100+ lung cancer cases were obtained from Medline and other sources. Studies were classified as principal, or subsidiary where cases overlapped with principal studies. Data were extracted on design, exposures, histological types and confounder adjustment. RRs/ORs and 95% CIs were extracted for ever, current and ex smoking of cigarettes, pipes and cigars and indices of cigarette type and dose-response. Meta-analyses and meta-regressions investigated how relationships varied by study and RR characteristics, mainly for outcomes exactly or closely equivalent to all lung cancer, squamous cell carcinoma ("squamous") and adenocarcinoma ("adeno").

287 studies (20 subsidiary) were identified. Although RR estimates were markedly heterogeneous, the meta-analyses demonstrated a relationship of smoking with lung cancer risk, clearly seen for ever smoking (random-effects RR 5.50, CI 5.07-5.96) current smoking (8.43, 7.63-9.31), ex smoking (4.30, 3.93-4.71) and pipe/cigar only smoking (2.92, 2.38-3.57). It was stronger for squamous (current smoking RR 16.91, 13.14-21.76) than adeno (4.21, 3.32-5.34), and evident in both sexes (RRs somewhat higher in males), all continents (RRs highest for North America and lowest for Asia, particularly China), and both study types (RRs higher for prospective studies). Relationships were somewhat stronger in later starting and larger studies. RR estimates were similar in cigarette only and mixed smokers, and similar in smokers of pipes/cigars only, pipes only and cigars only. Exceptionally no increase in adeno risk was seen for pipe/cigar only smokers (0.93, 0.62-1.40). RRs were unrelated to mentholation, and higher for non-filter and handrolled cigarettes. RRs increased with amount smoked, duration, earlier starting age, tar level and fraction smoked and decreased with time quit. Relationships were strongest for small and squamous cell, intermediate for large cell and weakest for adenocarcinoma. Covariate-adjustment little affected RR estimates.

The association of lung cancer with smoking is strong, evident for all lung cancer types, dose-related and insensitive to covariate-adjustment. This emphasises the causal nature of the relationship. Our results quantify the relationships more precisely than previously.

Although tobacco use has been recognized as one of the leading causes of cancer morbidity and mortality, a role of smoking in the occurrence of prostate cancer has not been established. However, evidence indicates that factors that influence the incidence of prostate cancer may differ from those that influence progression and fatality from the disease. Thus, we reviewed and summarized results from prospective cohort studies that assessed the relation between smoking and fatal prostate cancer risk, as well as epidemiological and clinical studies that focused on aggressive behavior in prostate cancer, such as poorer survival, advanced stage, or poorer differentiation at diagnosis. The majority of the prospective cohort studies showed that current smoking is associated with a moderate increase of ~30% in fatal prostate cancer risk compared to never/non-smokers. This association is likely to be an underestimate of the effect of smoking because most studies had a single assessment of smoking at baseline and long follow-up times, and the association was considerably stronger in some sub-groups of heaviest smokers, or when smoking was assessed in a relatively short period (within 10 years) prior to cancer mortality. Using aggressive behavior of prostate cancer as outcome, current smoking was associated with significantly elevated risk, ranging from around twofold to threefold or higher. Although alternative explanations, such as publication bias, residual confounding, screening bias, and the influence of smoking-related comorbidities cannot be ruled out entirely, these findings suggest that smoking is associated with aggressive behavior of prostate cancers or with a sub-group of rapidly progressing prostate cancer. Based on evidence presented in this review, cigarette smoking is likely to be a risk factor for prostate cancer progression and should be considered as a relevant exposure in prostate cancer research and prevention of mortality from this cancer.

Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.

Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.

Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.

The results confirm and quantify the causal relationships with smoking.

Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole.

Newfoundland and Labrador (NL) has the highest incidence rate of both colorectal cancer (CRC) and smoking prevalence in Canada. The objective of this study was to examine if CRC is associated with smoking in this population.

Newly diagnosed cases identified between 1999 and 2003 were frequency-matched by 5-year age group and sex with controls selected from the residents of NL through random digit dialing. A total of 702 cases and 717 controls consented to participate in the study and completed a set of self-administered questionnaires. Measures of tobacco use included type of tobacco, age of initiation of smoking, years of smoking, years since started smoking, number of cigarettes smoked daily, pack years, and years since abstention from smoking. Odds ratios were estimated using multivariate logistic regression.

In comparison with non-smokers, former and current smokers were at a significantly elevated risk of CRC with corresponding odds ratios of 1.36 and 1.96. The risk significantly increased with cigarette smoking years, the amount of cigarettes smoked daily, and cigarette pack years. The risk significantly decreased with years of abstention from smoking cigarettes. This association was stronger among drinkers and in men. In addition, this effect was observed to be slightly stronger for rectum than colon cancer.

In summary, cigarette smoking increased the risk of CRC in the NL population. The risk of CRC associated with cigarette smoking varies by sex, drinking status, and site of CRC.

The carcinogenicity of cigar and pipe smoking is established but the effect of detailed smoking characteristics is less well defined. We examined the effects on cancer incidence of exclusive cigar and pipe smoking, and in combination with cigarettes, among 102,395 men from Denmark, Germany, Spain, Sweden and the United Kingdom in the EPIC cohort. Hazard ratios (HR) and their 95% confidence intervals (CI) for cancer during a median 9-year follow-up from ages 35 to 70 years were estimated using proportional hazards models. Compared to never smokers, HR of cancers of lung, upper aerodigestive tract and bladder combined was 2.2 (95% CI: 1.3, 3.8) for exclusive cigar smokers (16 cases), 3.0 (2.1, 4.5) for exclusive pipe smokers (33 cases) and 5.3 (4.4, 6.4) for exclusive cigarette smokers (1,069 cases). For each smoking type, effects were stronger in current smokers than in ex-smokers and in inhalers than in non-inhalers. Ever smokers of both cigarettes and cigars [HR 5.7 (4.4, 7.3), 120 cases] and cigarettes and pipes [5.1 (4.1, 6.4), 247 cases] had as high a raised risk as had exclusive cigarette smokers. In these smokers, the magnitude of the raised risk was smaller if they had switched to cigars or pipes only (i.e., quit cigarettes) and had not compensated with greater smoking intensity. Cigar and pipe smoking is not a safe alternative to cigarette smoking. The lower cancer risk of cigar and pipe smokers as compared to cigarette smokers is explained by lesser degree of inhalation and lower smoking intensity.

Cigarette smoking is the major cause of chronic obstructive pulmonary disease, but studies on the contribution of other smoking techniques are sparse.

To determine whether pipe and cigar smoking was associated with elevated cotinine levels, decrements in lung function, and increased odds of airflow obstruction.

Cross-sectional study.

Population-based sample from 6 U.S. communities.

Men and women aged 48 to 90 years without clinical cardiovascular disease at enrollment who were part of MESA (Multi-Ethnic Study of Atherosclerosis).

The MESA Lung Study measured spirometry according to American Thoracic Society guidelines and urine cotinine levels by immunoassay on a subsample of MESA. Pipe-years and cigar-years were calculated as years from self-reported age of starting to age of quitting (or to current age in current users) multiplied by pipe-bowls or cigars per day.

Of 3528 participants, 9% reported pipe smoking (median, 15 pipe-years), 11% reported cigar smoking (median, 6 cigar-years), and 52% reported cigarette smoking (median, 18 pack-years). Self-reported current pipe and cigar smokers had elevated urine cotinine levels compared with never-smokers. Pipe-years were associated with decrements in FEV(1), and cigar-years were associated with decrements in the FEV(1)-FVC ratio. Participants who smoked pipes or cigars had increased odds of airflow obstruction whether they had also smoked cigarettes (odds ratio, 3.43 [95% CI, 1.75 to 6.71]; P < 0.001) or not (odds ratio, 2.31 [CI, 1.04 to 5.11]; P = 0.039) compared with participants with no smoking history.

Cross-sectional design.

Pipe and cigar smoking increased urine cotinine levels and was associated with decreased lung function and increased odds of airflow obstruction, even in participants who had never smoked cigarettes.

National Heart, Lung, and Blood Institute, National Institutes of Health.

Prostate cancer has few known risk factors. As part of a population-based case-control study conducted in four health maintenance organizations, the authors examined the associations between fatal prostate cancer and several medical and behavioral characteristics.

Cases were 768 health plan members who died of prostate adenocarcinoma during the period 1997-2001. We randomly selected controls (929) from the health plan membership and matched them to cases on health plan, age, race, and pattern of health plan membership. We examined medical records to obtain information on potential risk factors during the 10 years before the date on which prostate cancer was first suspected; the same reference date was used for the matched controls.

Anthropometric characteristics, as well as personal histories of benign prostatic hypertrophy, transurethral prostatectomy, cancer, diabetes, prostatitis, hypertension, and vasectomy were largely similar for cases and controls. Men who died from prostate cancer were more likely than controls to have been cigarette smokers according to the most recent smoking notation before the reference date (odds ratio 1.5, 95% confidence interval 1.1-2.0).

The observed increase in risk associated with recent cigarette smoking is consistent with the findings of several other studies. However, in contrast with some reports, we observed no connection between fatal prostate cancer and some prior health conditions or measures of body size.

Whereas the International Agency for Research on Cancer (IARC) Monograph concluded that the evidence for the relationship between cigarette smoking and liver cancer is sufficient, the US Surgeon General's report summarized the data as suggestive but not sufficient.

A meta-analysis of previous epidemiologic studies may help to clarify the potential association. We identified 38 cohort studies and 58 case-control studies in a systematic literature search for studies on liver cancer and cigarette smoking. The meta-relative risk (mRR) of liver cancer and dose-response trends were calculated. Tests for heterogeneity, publication bias assessment and influence analyses were performed.

Compared with never smokers, the adjusted mRR was 1.51 [95% confidence interval (CI) 1.37-1.67] for current smokers and 1.12 (95% CI 0.78-1.60) for former smokers. The increased liver cancer risk among current smokers appeared to be consistent in strata of different regions, study designs, study sample sizes and publication periods.

The results of our meta-analysis show that tobacco smoking is associated with liver cancer development, which supports the conclusion by the IARC Monograph. This conclusion has an important public health message for areas with high smoking prevalence and high liver cancer incidence such as China.

We evaluated the relationship between smoking and adenocarcinoma of the prostate.

We pooled data from 24 cohort studies enrolling 21 579 prostate cancer case participants for a general variance-based meta-analysis. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated separately for mortality and incidence studies. We tested the robustness of effect measures and evaluated statistical heterogeneity with sensitivity analyses.

In the pooled data, current smokers had no increased risk of incident prostate cancer (RR = 1.04; 95% CI = 0.87, 1.24), but in data stratified by amount smoked they had statistically significant elevated risk (cigarettes per day or years: RR = 1.22; 95% CI = 1.01, 1.46; pack years of smoking: RR = 1.11; 95% CI = 1.01, 1.22). Former smokers had an increased risk (RR = 1.09; 95% CI = 1.02, 1.16). Current smokers had an increased risk of fatal prostate cancer (RR = 1.14; 95% CI = 1.06, 1.19). The heaviest smokers had a 24% to 30% greater risk of death from prostate cancer than did nonsmokers.

Observational cohort studies show an association of smoking with prostate cancer incidence and mortality. Ill-defined exposure categories in many cohort studies suggest that pooled data underestimate risk.

This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed.

The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case-control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1-3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3-25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2-429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2-57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.

We develop a mixed model to capture the complex stochastic nature of tobacco abuse and dependence. This model describes transition processes among addiction and nonaddiction stages. An important innovation of our model is allowing an unobserved cure state, or permanent quitting, in contrast to transient quitting. This distinction is necessary to model data from situations where censoring prevents unambiguous determination that a person has been "cured." Moreover, the processes that describe transient and permanent quitting are likely to be different and have different policy-making implications. For example, when analyzing factors that influence smoking and can be targeted by interventions, it is more important to target those factors that are associated with permanent quitting rather than transient quitting.We apply our methodology to the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a large (29,133 participants) longitudinal cohort study. While ATBC was designed as a cancer prevention study, it contains unique information about the smoking status of each participant during every 4-month period of the study. These data are used to model smoking cessation patterns using a discrete-time stochastic mixed-effects model with three states: smoking, transient cessation, and permanent cessation (absorbent state). Random participant-specific transition probabilities among these states are used to account for participant-to-participant heterogeneity. Another important innovation in our article is to design computationally practical methods for dealing with the size of the dataset and complexity of the models. This is achieved using the marginal likelihood obtained by integrating over the Beta distribution of random effects.

We conducted a systematic review of studies addressing the relation between cigarette smoking and gastric cancer to estimate the magnitude of the association for different levels of exposure and cancer locations.

Published cohort, case-cohort, and nested case-control studies were identified through PubMed, Scopus, and Web of Science searches, from inception to July 2007. Relative risk (RR) estimates referring to the comparison of two categories of exposure (e.g., current smokers vs. never smokers) were combined using a random effects model. Generalized least squares regression was used for trend estimation. Heterogeneity was quantified using the I (2) statistic.

Forty-two articles were considered for the systematic review. Comparing current smokers with never smokers: the summary RR estimates were 1.62 in males (95% CI: 1.50-1.75; I (2) = 46.0%; 18 studies) and 1.20 in females (95% CI: 1.01-1.43; I (2) = 49.8%; nine studies); the RR increased from 1.3 for the lowest consumptions to 1.7 for the smoking of approximately 30 cigarettes per day in the trend estimation analysis; smoking was significantly associated with both cardia (RR = 1.87; 95% CI: 1.31-2.67; I (2) = 73.2%; nine studies) and non-cardia (RR = 1.60; 95% CI: 1.41-1.80; I (2) = 18.9%; nine studies) cancers.

Our study provides solid evidence to classify smoking as the most important behavioral risk factor for gastric cancer.

Pancreatic cancer is an aggressive disease with a poor prognosis. Hereditary factors have been reported in up to 10% of cases of pancreatic cancer. The clinical characteristics and genetic abnormalities have been identified for a proportion of this high-risk group, and the development of preventive strategies for these individuals is now a primary goal of cancer clinicians.

A review of the current literature regarding the genetics, screening, and prevention of pancreatic cancer and its precursor lesions was undertaken.

Risk factors for pancreatic cancer include smoking, chronic pancreatitis, and a genetic predisposition. The role of diabetes or a diet high in fat or meat remains unclear. The genetic mutations that accompany pancreatic cancer appear to occur in a temporal sequence, beginning in the earliest of precursor lesions. These mutations are detectable in pancreatic juice and, in conjunction with imaging, form the basis of screening programs for high-risk individuals. Not all precursor lesions will undergo malignant transformation, and testing is currently limited in its ability to determine which lesions will undergo transformation.

Avoiding tobacco smoking and minimizing risk factors associated with chronic pancreatitis are recommended to reduce the risk of pancreatic cancer. Individuals with a high-risk genetic background require counseling, genetic testing if appropriate (BRCA2 mutation or p16INK4A inactivity) and secondary screening for pancreatic cancer in specialist centers. Risk stratification will improve as more genetic abnormalities causing pancreatic cancer are defined.

Controversial information is available with reference to the role of type or yield of cigarettes on the risk of cardiovascular disease.

We considered the issue in a combined dataset of three case-control studies of acute myocardial infarction conducted in Italy between 1983 and 2003.

Cases were 1990 subjects with a first episode of non-fatal acute myocardial infarction, and controls were 2521 patients in hospital for acute diseases unrelated to smoking or other recognized risk factors for myocardial infarction. The odds ratio and the corresponding 95% confidence interval (CI) were derived by unconditional multiple logistic regression models, including terms for age, sex, and several major risk factors for myocardial infarction.

As compared to never smokers, the multivariate odds ratio was 2.70 (95% CI 2.01-3.63) for smokers of low tar cigarettes (<10 mg), 3.06 (95% CI 2.53-3.70) for intermediate (10-19 mg) and 3.14 (95% CI 2.12-4.64) for high tar yield (> or =20 mg). After further allowance for duration of smoking and number of cigarettes per day, as compared to low tar yield cigarettes, the odds ratio was 1.14 (95% CI 0.85-1.53) for intermediate, and 1.28 (95% CI 0.81-2.02) for high tar yield.

Our study confirms that no substantial reduction in acute myocardial infarction risk resulted from the decrease of cigarette tar yield.

Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tract, but quantification of the risk for exclusive pipe smokers is still limited. To analyse the association between exclusive pipe smoking and cancers of the upper digestive tract, we used data from a series of case-control studies conducted in Italy and Switzerland between 1984 and 1999. After excluding cigarette and cigar smokers, 41 male oral and pharyngeal cancer cases, 52 male oesophageal cancer cases and 1,032 male controls were included in the present analysis. Odds ratios (OR) of cancers were estimated by the mean of unconditional multivariate logistic regression, including terms for age, study centre, education, body mass index, and alcohol drinking. Compared to never smokers, exclusive pipe smokers had an OR of 8.7 [95% confidence intervals (CI): 4.0-18.9] of all upper digestive tract cancers. The OR was 12.6 for oral and pharyngeal and 7.2 for oesophageal cancer. Pipe smokers who were also heavy alcohol drinkers had an OR of 38.8 (95% CI: 13.6-110.9) as compared to never smokers and light drinkers. Thus, pipe smoking and heavy alcohol drinking appears to interact at least on a multiplicative model.

The epidemiologic studies on oesophageal cancer and smoking cessation published before December 2005 were reviewed here. The results from at least 10 cohort and 10 case-control studies indicated that former smokers had a lower risk of squamous-cell or unspecified oesophageal cancer than current smokers. Most investigations showed that the risk of oesophageal cancer remains elevated many years (at least 10) after cessation of smoking, to decline by about 40% only thereafter. Moreover, after 10 years since cessation of smoking, ex-smokers still have a twofold increased risk as compared to never smokers. A few studies investigated the effect of smoking cessation on adenocarcinoma, and did not report a clear reduction of risk. Data on oesophageal adenocarcinoma are however too limited to provide adequate inference on the relation with time since smoking cessation. In conclusion, cessation of smoking could have an appreciable impact in reducing (squamous-cell) oesophageal cancer, and represents an obvious priority for prevention and public-health purposes.

We analyzed risk while adjusting for age, body mass index, frequency of moderate physical activity, alcohol consumption, preference for vegetables versus meats, and frequency of meat consumption in a multivariate analysis and based our findings on not mortality data but incidence data. 733,134 Korean men who were 30 years old or older, insured by the National Health Insurance Corporation, and had a medical evaluation in 1996 were included in the study and followed up through 2000. During the 4-year follow-up period of 3,590,872 person-years, we identified 7204 new cases. We used the Cox proportional hazards model to estimate adjusted relative risks (aRRs), 95% confidence intervals (CIs). The association of current cigarette smoking was significantly stronger as compared with never smokers; aRR was 1.49 (95% CI=1.39-1.59) for all cancers, 4.46 (2.32-8.57) for esophageal, 3.83 (2.97-4.94) for lung, 3.01 (1.58-5.72) for laryngeal, 2.24 (1.48-3.39) for urinary bladder, 1.62 (1.42-1.84) for gastric, 1.75 (1.12-2.74) for oral and pharyngeal, 1.58 (0.97-2.27) for pancreatic, and 1.50 (1.29-1.74) for liver cancer. Our findings, based on incidence data, confirmed that differences in smoking habit were responsible for most of the differences observed in smoking-related cancers.

This prospective study of the elderly population estimated the risks of smoking for morbidity and mortality and identified whether cessation of smoking reduced the risk of disease. Data came from face-to-face interviews that used a population-based probability sample of those aged 60 years or over in Taiwan, provided by the Population and Health Research Center, Bureau of Health Promotion. In total, 4,049 subjects were included at the baseline year of 1989 and followed up in 1993 and 1996. Smoking-related variables included current smoking status, smoking history, daily consumption, and years since the cessation of smoking. Cox regression models were used to analyze the relative risks for morbidity and mortality, controlling for demographics, physical function, and comorbidities. The sample was made up of 50.2% nonsmokers, 15.2% ex-smokers, and 34.6% current smokers in the baseline year. Current smokers were more likely to have lower respiratory tract diseases throughout the study. Current smokers had a higher risk of stroke from 1989 to 1993. No dose-response relationship for smoking exposure or impact of years since smoking cessation was found. Whether cessation of smoking is protective should be investigated for middle-aged adults followed to old age. An effective strategy for smoking cessation in the elderly is suggested, and people should be encouraged to quit smoking at any time.

Although many studies have examined the adverse health effects of pipe smoking combined with other forms of tobacco use, few have included large numbers of exclusive pipe smokers. The prevalence of pipe smoking has declined since the 1960s, yet usage is still common regionally, especially among older populations.

Using Cox proportional hazards models, we examined the association between pipe smoking and mortality from tobacco-related cancers and other diseases in a cohort of U.S. men enrolled in the Cancer Prevention Study II, an American Cancer Society prospective study. The cohort of 138 307 men included those who reported, in their 1982 enrollment questionnaire, exclusive current or former use of pipes (n = 15,263 men) or never use of any tobacco product (n = 123,044 men). Analyses were based on 23 589 men who died during 18 years of follow-up.

Current pipe smoking, compared with never use of tobacco, was associated with an increased risk of death from cancers of the lung (relative risk [RR] = 5.00, 95% confidence interval [CI] = 4.16 to 6.01), oropharynx (RR = 3.90, 95% CI = 2.15 to 7.08), esophagus (RR = 2.44, 95% CI = 1.51 to 3.95), colorectum (RR = 1.41, 95% CI = 1.15 to 1.73), pancreas (RR = 1.61, 95% CI = 1.24 to 2.09), and larynx (RR = 13.1, 95% CI = 5.2 to 33.1), and from coronary heart disease (RR = 1.30, 95% CI = 1.18 to 1.43), cerebrovascular disease (RR = 1.27, 95% CI = 1.09 to 1.48), and chronic obstructive pulmonary disease (RR = 2.98, 95% CI = 2.17 to 4.11). These risks were generally smaller than those associated with cigarette smoking and similar to or larger than those associated with cigar smoking. Relative risks of lung cancer showed statistically significant increases with number of pipes smoked per day, years of smoking, and depth of inhalation and decreases with years since quitting.

Results from this large prospective study suggest that pipe smoking confers a risk of tobacco-associated disease similar to cigar smoking.

Cigarette smoking is an important and well-established cause of pancreatic cancer. In contrast, little is known about the effects of smoking cigars, pipes, and use of smokeless tobacco on pancreatic cancer risk. The objective of the present study was to examine the association between noncigarette tobacco use (i.e., cigars, pipes, smokeless tobacco) and pancreatic cancer risk among nonsmokers of cigarettes. A population-based case-control study of pancreatic cancer was conducted during 1986-1989 among residents of Atlanta, Georgia, Detroit, Michigan, and 10 counties in New Jersey. Direct interviews were successfully completed with 526 newly diagnosed pancreatic cancer patients and 2153 controls ages 30-79 years. This analysis was restricted to lifelong nonsmokers of cigarettes and based on interviews with 154 cases newly diagnosed with carcinoma of the exocrine pancreas and 844 population controls who reported no history of cigarette smoking. We observed a consistent pattern of increased risk associated with cigar smoking, although these elevations were not statistically significant. Participants who smoked cigars regularly (i.e., at least one cigar/week for >/=6 months) experienced a 70% increased risk [95% confidence interval (CI): 0.9-3.3], and those who never used other form of tobacco had a 90% increased risk (95% CI: 0.8-4.3). Risk was elevated among those who smoked more than one cigar/day [odds ratio (OR) = 1.8; 95% CI: 0.8-4.2) and among those who smoked cigars > 20 years (OR = 1.9; 95% CI: 0.9-3.9). Trends in risk with increasing amount and duration smoked were consistent but not statistically significant (P = 0.17 and P = 0.16, respectively). Subjects who used smokeless tobacco regularly had a 40% increased risk of pancreatic cancer (95% CI: 0.5-3.6) compared with nonusers of tobacco. We observed a marginally significant increasing risk with increased use of smokeless tobacco (P = 0.04); participants who used >2.5 oz of smokeless tobacco a week had an OR of 3.5 (95% CI: 1.1-11). Long-term use of smokeless tobacco (i.e., >20 years) was also associated with a nonsignificant increased risk (OR = 1.5; 95% CI: 0.6-4.0). In contrast, pipe smokers experienced no increased risk (OR = 0.6; 95% CI: 0.1-2.8). Our results suggest that heavy use of smokeless tobacco, and to a lesser extent, cigar smoking may increase the risk of pancreatic cancer among nonsmokers of cigarettes.

Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.

Pipe and cigar smoking are still regarded by many as less hazardous to health than cigarette smoking.

Prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns with mean follow-up of 21.8 years. The outcome measures include major coronary heart disease (CHD) and stroke events, cancer incidence, and deaths from all causes.

There were 1133 major CHD events and 440 stroke events, 919 new cancers and 1994 deaths from all causes in the 7121 men with no diagnosed CHD, stroke, diabetes, or cancer at screening. Compared with never smokers, pipe/cigar smokers (primary and secondary combined) showed significantly higher risk of major CHD events (relative risk [RR] = 1.69, 95% CI: 1.32, 2.14) and stroke events (RR = 1.62, 95% CI: 1.08, 2.41) and of cardiovascular, non-cardiovascular, and total mortality (RR = 1.49, 95% CI: 1.13, 1.96, RR = 1.40, 95% CI: 1.08, 1.83 and RR = 1.44, 95% CI: 1.19, 1.74, respectively), after adjustment for lifestyle and biological characteristics. They also showed a significantly higher incidence of smoking-related cancers (RR = 2.67, 95% CI: 1.70, 4.26), largely due to lung cancer (RR = 4.35, 95% CI: 2.05, 8.94). Overall, the effects in pipe/cigar smokers were intermediate between never-smokers and light cigarette smokers, although risks for lung cancer were similar to light cigarette smokers.

Pipe and cigar smoking, whether primary or secondary, carries significant risk of smoking-related ill health.

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. Genetic research on CAD has traditionally focused on investigation aimed at identifying disease-susceptibility genes. Recent evidence suggests that somatically acquired DNA mutations may also contribute significantly to the pathogenesis of the disease, underlining the similarity between atherosclerotic and carcinogenic processes. The generation of oxidative stress has been emphasized as an important cause of DNA damage in atherosclerosis. This review highlights some of the major atherogenic risk factors as likely mediators in the oxidative modification of DNA. It also examines the hypothesis that an increase in oxidative stress may derive from "oxidatively" damaged mitochondria. Accordingly, further research in this field should be given high priority, since increased somatic DNA damage could be an important pathogenic factor and an additional prognostic predictor, as well as a potential target for therapeutic strategies in coronary artery disease.

Cigarette smoking is associated with increased risk of stomach cancer in many studies but there are limited data on this relationship in women and on risk associated with use of tobacco products other than cigarettes. We examined stomach cancer death rates in relation to cigarette smoking in women and use of cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective mortality study in the United States (US). Cohort follow-up from 1982-96 identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women, respectively. Cox proportional hazards models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent group. Multivariate-adjusted RRs were the highest for men who currently smoked cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75-2.67) and both increased with smoking duration. Women who currently (RR = 1.49, 95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes were at significantly increased risk, as were men who formerly smoked cigarettes (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men who reported a history of chronic indigestion or gastroduodenal ulcer had substantially higher mortality rates associated with current cigarette (RR = 3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as did men who were current aspirin users. If causal, the estimated proportion of stomach cancer deaths attributable to tobacco use would be 28% in US men and 14% in women. We conclude that prolonged use of tobacco products is associated with increased stomach cancer mortality in men and women. The accumulated evidence from this and other studies support reconsidering stomach cancer as a tobacco-related cancer.

Primary prevention of colonic adenomas and cancer through dietary interventions or chemoprevention has great appeal. This article discusses primary prevention goals and promising nutritional or chemopreventive strategies. There is substantial observational evidence that diets high in total calories and fat and or low in fruits and vegetables or total fiber as well as low levels of physical activity are related to the risk of colonic neoplasia. Similar observational data indicate that diets high in specific nutrients such as antioxidant vitamins or calcium may be protective. The article describes some of the newer chemopreventive agents and reviews the data linking diet and lifestyle to colorectal cancer risk, focusing on interventions that have also been studied in prospective clinical trials. Finally the evidence supporting the role of non-steroidal anti-inflammatory drugs for the chemoprevention of CRC is reviewed and the status of several other promising newer agents that are entering human trials is summarized.

To assess the relation between air pollution with airway irritants, including sulfuric acid and lung cancer, a case-control study was performed near an industry producing sulfuric acid and fertilizers in Kedainiai county, central Lithuania. The county had the highest lung cancer rates of the country among men. Between 1967 and 1973, the levels of sulfuric acid exceeded 500 microg/m(3) within 2 km of the industry and 100 microg/m(3) more than 5 km away. A total of 277 men who were diagnosed as having lung cancer during 1981-1991 in Kedainiai county were included as well as 1,108 population controls. Information on residential history since 1960, smoking habits, occupations and workplaces during lifetime was obtained from questionnaires mailed to next-of-kin. The relative risk of lung cancer associated with living within approximately 5 km from the plant was 1.02 (95% CI: 0.76-1.38) compared to those who had never lived in this area. No relation with distance or duration of residence was observed. Furthermore, workers at the plant did not have an increased lung cancer risk. The relative risk of lung cancer associated with smoking was 21.2 (95% CI: 7.51; 60.1) for current smokers and 14.0 (95% CI: 4.88; 40.3) for exsmokers. The duration of smoking, a low age at start and amount of cigarettes smoked daily were positively associated with lung cancer risk. Smoking levels appeared more pronounced among study controls than in the rest of the country. Our study could not confirm earlier evidence of an association between exposure to airway irritants, such as sulfuric acid and lung cancer. Smoking is the major determinant of the risk of lung cancer in men in Kedainiai county. It is probable that higher smoking rates constitute the main reason for the increased lung cancer risk among men in this area.

It is still unclear if men and women are equally susceptible to the hazards of tobacco smoking. The objective of this study was to examine smoking related mortality among men and women.

In 1963 a questionnaire concerning tobacco smoking habits was sent out to a random sample from the 1960 Swedish census population. Date and cause of death have been collected for the deceased in the cohort through 1996.

Sweden.

The survey included a total of 27 841 men and 28 089 women, aged 18-69 years. The response rate was 93.1% among the men and 95.4% among the women.

After adjustment for age and place of residence positive associations were found between cigarette smoking and mortality from ischaemic heart disease, aortic aneurysm, bronchitis and emphysema, cancer of the lung, upper aerodigestive sites, bladder, pancreas in both men and women, but not from cerebrovascular disease. When the effect of amount of the cigarette consumption was considered, female smokers displayed, for example, slightly higher relative death rates from ischaemic heart disease. However, no statistically significant gender differential in relative mortality rates was observed for any of the studied diseases.

Women and men in this Swedish cohort seem equally susceptible to the hazards of smoking, when the gender differential in smoking characteristics is accounted for. Although the cohort under study is large, there were few female smokers in the high consuming categories and the relative risk estimates are therefore accompanied by wide confidence intervals in these categories.

According to the "monoclonal hypothesis" of atherosclerosis, several studies suggest that cancer and atherosclerosis may have several fundamental biological mechanisms in common. Therefore, an increase in the mutation rate may be involved in the pathogenesis of atherosclerotic plaques. The aim of the study was to verify the presence of chromosomal damage in peripheral blood lymphocytes in patients with coronary artery disease by using micronucleus (MN) test, a reliable biomarker in genetic and cancer risk assessment. Subjects included 53 patients with documented coronary ischemic heart disease (group I); 10 patients with valvular heart disease in absence of atherosclerotic lesions of the coronary arteries (group II) and 16 healthy subjects, age- and sex-matched (group III) were studied as controls. For each subject, two separate cultures were performed and 1000 binucleated cells were scored for the evaluation of MN frequency. The mean (+/-S.E.M.) of MN frequency were 11.9+/-1.7, 5.9+/-1.2 and 3.6+/-0.7 in groups I, II and III, respectively. The MN frequency of group I was significantly higher than that of group III (P=0.02). In group I, MN frequency increased with the number of affected vessels (6.3+/-0.7, 13.9+/-1.6, 14.9+/-5.3 for one-, two-, and three-vessel disease, respectively). Scheffe's test showed that MN frequency was significantly higher in two-vessel compared with one-vessel disease (P=0.0077). Moreover, a positive relationship was found between MN levels and the severity of the disease, calculated by the Duke scoring system (R=0.28, P=0.032), as well as the systolic blood pressure (R=0.34, P=0.009). These results suggest that coronary artery disease in humans is a condition characterized by an increase of DNA damage, positively correlated with the severity of the atherosclerotic disease.

We conducted a population-based case-control study among men 40-75 years of age encompassing all cases of lung cancer 1985-1990 among stable residents of Stockholm County 1950-1990. Questionnaires to subjects or next-of-kin (primarily wives or children) elicited information regarding smoking and other risk factors, including occupational and residential histories. A high response rate (>85%) resulted in 1,042 cases and 2,364 controls. We created retrospective emission databases for NOx/NO2 and SO2 as indicators of air pollution from road traffic and heating, respectively. We estimated local annual source-specific air pollution levels using validated dispersion models and we linked these levels to residential addresses using Geographical Information System (GIS) techniques. Average traffic-related NO2 exposure over 30 years was associated with a relative risk (RR) of 1.2 (95% confidence interval 0.8-1.6) for the top decile of exposure, adjusted for tobacco smoking, socioeconomic status, residential radon, and occupational exposures. The data suggested a considerable latency period; the RR for the top decile of average traffic-related NO2 exposure 20 years previously was 1.4 (1.0-2.0). Little association was observed for SO2. Occupational exposure to asbestos, diesel exhaust, and other combustion products also increased the risk of lung cancer. Our results indicate that urban air pollution increases lung cancer risk and that vehicle emissions may be particularly important.

This case-referent study investigated the lung cancer risk from occupational exposure to diesel exhaust, mixed motor exhaust, other combustion products, asbestos, metals, oil mist, and welding fumes. All cases of lung cancer in males aged 40-75 years among stable residents of Stockholm County, Sweden, were identified from 1985 to 1990. Referents were selected as a stratified (age, inclusion year) random sample. Information on lifetime occupational history, residency, and tobacco smoking was obtained from the study subjects or from next of kin. Response rates of 87% and 85% resulted in 1,042 cases and 2,364 referents, respectively. Occupational exposures were assessed by an occupational hygienist who coded the intensity and probability of each exposure. Risk estimates were adjusted for tobacco smoking, other occupational exposures, residential radon, and environmental exposure to traffic-related air pollution. For the highest quartile of cumulative exposure versus no exposure, the relative risk was 1.63 (95% confidence interval (CI): 1.14, 2.33) for diesel exhaust, 1.60 (95% CI: 1.09, 2.34) for combustion products, and 1.68 (95% CI: 1.15, 2.46) for asbestos. Dose-response analyses indicated an increase in lung cancer risk of 14% per fiber-year/ml for asbestos exposure. No increased risk was found for the other exposure factors. An overall attributable proportion of 9.5% (95% CI: 5.5, 13.9) was estimated for lung cancer related to diesel exhaust, other combustion products, and asbestos.