Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer. Other factors include avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. A substantial reduction in breast cancer is likely to require modification of sex hormone levels, and development of practical methods for doing so is a high research priority. Resolution of the potential protective roles of specific antioxidants and other constituents of fruits and vegetables deserves major attention. Mechanistic studies of carcinogenesis indicate an important role of endogenous oxidative damage to DNA that is balanced by elaborate defense and repair processes. Also key is the rate of cell division, which is influenced by hormones, growth, cytotoxicity, and inflammation, as this determines the probability of converting DNA lesions to mutations. These mechanisms may underlie many epidemiologic observations.

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The causes and prevention of cancer.

Summary Background Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. Methods This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Eff ects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffi c indicators. We used Cox regression models with adjustment for potential confounders for cohort-specifi c analyses and random eff ects models for meta-analyses. Findings The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically signifi cant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03–1·45] per 10 μg/m³). For PM2·5 the HR was 1·18 (0·96–1·46) per 5 μg/m³. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10–2·08) and 1·55 (1·05–2·29), respectively. An increase in road traffi c of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99–1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95–1·07] per 20 μg/m³) or traffi c intensity on the nearest street (HR 1·00 [0·97–1·04] per 5000 vehicles per day).

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Air pollution and lung cancer incidence in 17 European cohorts : Prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Air pollution has been considered a hazard to human health. In the past decades, many studies highlighted the role of ambient airborne particulate matter (PM) as an important environmental pollutant for many different cardiopulmonary diseases and lung cancer. Numerous epidemiological studies in the past 30 years found a strong exposure-response relationship between PM for short-term effects (premature mortality, hospital admissions) and long-term or cumulative health effects (morbidity, lung cancer, cardiovascular and cardiopulmonary diseases, etc). Current research on airborne particle-induced health effects investigates the critical characteristics of particulate matter that determine their biological effects. Several independent groups of investigators have shown that the size of the airborne particles and their surface area determine the potential to elicit inflammatory injury, oxidative damage, and other biological effects. These effects are stronger for fine and ultrafine particles because they can penetrate deeper into the airways of the respiratory tract and can reach the alveoli in which 50% are retained in the lung parenchyma. Composition of the PM varies greatly and depends on many factors. The major components of PM are transition metals, ions (sulfate, nitrate), organic compound, quinoid stable radicals of carbonaceous material, minerals, reactive gases, and materials of biologic origin. Results from toxicological research have shown that PM have several mechanisms of adverse cellular effects, such as cytotoxicity through oxidative stress mechanisms, oxygen-free radical-generating activity, DNA oxidative damage, mutagenicity, and stimulation of proinflammatory factors. In this review, the results of the most recent epidemiological and toxicological studies are summarized. In general, the evaluation of most of these studies shows that the smaller the size of PM the higher the toxicity through mechanisms of oxidative stress and inflammation. Some studies showed that the extractable organic compounds (a variety of chemicals with mutagenic and cytotoxic properties) contribute to various mechanisms of cytotoxicity; in addition, the water-soluble faction (mainly transition metals with redox potential) play an important role in the initiation of oxidative DNA damage and membrane lipid peroxidation. Associations between chemical compositions and particle toxicity tend to be stronger for the fine and ultrafine PM size fractions. Vehicular exhaust particles are found to be most responsible for small-sized airborne PM air pollution in urban areas. With these aspects in mind, future research should aim at establishing a cleared picture of the cytotoxic and carcinogenic mechanisms of PM in the lungs, as well as mechanisms of formation during internal engine combustion processes and other sources of airborne fine particles of air pollution.

Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms

4. Modelling Survival Data in Medical Research

https://www.surgonc.theclinics.com/article/S1055-3207(16)00003-X/pdf

Epidemiology of Lung Cancer.

The purpose of this study was to evaluate the relationship of long-term concentrations of ambient air pollutants and risk of incident lung cancer in nonsmoking California adults. A cohort study of 6,338 nonsmoking, non-Hispanic, white Californian adults, ages 27-95, was followed from 1977 to 1992 for newly diagnosed cancers. Monthly ambient air pollution data were interpolated to zip code centroids according to home and work location histories, cumulated, and then averaged over time. The increased relative risk (RR) of incident lung cancer in males associated with an interquartile range (IQR) increase in 100 ppb ozone (O3) was 3.56 [95% confidence interval (CI), 1.35-9.42]. Incident lung cancer in males was also positively associated with IQR increases for mean concentrations of particulate matter <10 microm (PM10; RR = 5.21; CI, 1.94-13.99) and SO2 (RR = 2.66; CI, 1.62-4.39). For females, incident lung cancer was positively associated with IQR increases for SO2 (RR = 2.14; CI, 1.36-3.37) and IQR increases for PM10 exceedance frequencies of 50 microg/m3 (RR = 1.21; CI, 0.55-2.66) and 60 microg/m3 (RR = 1.25; CI, 0.57-2.71). Increased risks of incident lung cancer were associated with elevated long-term ambient concentrations of PM10 and SO2 in both genders and with O3 in males. The gender differences for the O3 and PM10 results appeared to be partially due to gender differences in exposure.

Long-term concentrations of ambient air pollutants and incident lung cancer in California adults: results from the AHSMOG study.Adventist Health Study on Smog.

Cancer incidence and mortality in a cohort of 6000 nonsmoking California Seventh-Day Adventists were monitored for a 6-year period, and relationships with long-term cumulative ambient air pollution were observed. Total suspended particulates (TSP) and ozone were measured in terms of numbers of hours in excess of several threshold levels corresponding to national standards as well as mean concentration. For all malignant neoplasms among females, risk increased with increasing exceedance frequencies of all thresholds of TSP except the lowest one, and those increased risks were highly statistically significant. For respiratory cancers, increased risk was associated with only one threshold of ozone, and this result was of borderline significance. Respiratory disease symptoms were assessed in 1977 and again in 1987 using the National Heart, Lung and Blood Institute respiratory symptoms questionnaire on a subcohort of 3914 individuals. Multivariate analyses which adjusted for past and passive smoking and occupational exposures indicated statistically significantly (p less than 0.05) elevated relative risks ranging up to 1.7 for incidence of asthma, definite symptoms of airway obstructive disease, and chronic bronchitis with TSP in excess of all thresholds except the lowest one but not for any thresholds of ozone. A trend association (p = 0.056) was noted between the threshold of 10 pphm ozone and incidence of asthma. These results are presented within the context of standards setting for these constituents of air pollution.

Long-term ambient concentrations of total suspended particulates and oxidants as related to incidence of chronic disease in California Seventh-Day Adventists.

Cancer incidence among California seventh-day adventists, 1976-1982

Cancer incidence and mortality in a cohort of 6 000 Seventh-day Adventist nonsmokers who were residents of California were monitored for a 6-y period, and relationships with long-term ambient concentrations of total suspended particulates (TSPs) and ozone (O3) were studied. Ambient concentrations were expressed as mean concentrations and exceedance frequencies, which are the number of hours during which concentrations exceeded specified cutoffs (e.g., federal and California air quality standards). Risk of malignant neoplasms in females increased concurrently with exceedance frequencies for all TSP cutoffs, except the lowest, and these increased risks were highly statistically significant. An increased risk of respiratory cancers was associated with only one cutoff of O3, and this result was of borderline significance. These results are presented in the context of setting standards for these two air pollutants.

W L Beeson

Papers

Long-term concentrations of ambient air pollutants and incident lung cancer in California adults: results from the AHSMOG study.Adventist Health Study on Smog.

Long-term ambient concentrations of total suspended particulates and oxidants as related to incidence of chronic disease in California Seventh-Day Adventists.

Cancer incidence among California seventh-day adventists, 1976-1982

Ambient air pollution and cancer in California Seventh-day Adventists.

Long-term ambient concentrations of selected air pollutants and incident malignant neoplasms in california adults: results from the ahsmog study