Cancer mortality in the elderly in 11 countries worldwide, 1970-2015.

BACKGROUND: Population ageing results in an increasing cancer burden in the elderly. We aimed to evaluate time-trends in cancer mortality for adults aged 65 and over for 17 major cancer types and all cancers combined in 11 countries worldwide over the period 1970-2015. MATERIALS AND METHODS: We obtained cancer death certification and population figures from the WHO and PAHO databases. We computed age-standardised (world standard population) rates for individuals aged 65 and over, and applied joinpoint regression models. RESULTS: Age-standardised mortality rates for all cancers combined showed a heterogeneous, but widespread decline. Lung cancer mortality rates have been decreasing among men, and increasing among women. Pancreatic cancer had unfavourable trends in all countries for both sexes. Despite variability across countries, other tobacco-related cancers (except kidney) showed overall favourable trends, except in Poland and Russia. Age-standardised mortality rates from stomach cancer have been declining in all countries for both sexes. Colorectal mortality has been declining, except in Poland and Russia. Liver cancer mortality increased in all countries, except in Japan, France and Italy, which had the highest rates in the past. Breast cancer mortality decreased for most countries, except for Japan, Poland and Russia. Trends for age-standardised uterine cancer rates in the USA, Canada and the UK were increasing over the last decade. Ovarian cancer rates showed declines in most countries. With the exception of Russia, prostate cancer rates showed overall declines. Lymphoid neoplasms rates have been declining in both sexes, except in Poland and Russia. CONCLUSION: Over the last decades, age-standardised cancer mortality in the elderly has been decreasing in major countries worldwide and for major cancer sites, with the major exception of lung and uterine cancer in women and liver, pancreatic and kidney cancers in both sexes. Cancer mortality for the elderly in central and eastern Europe remains comparatively high.

Metformin Improves Survival in Patients with Pancreatic Ductal Adenocarcinoma and Pre-Existing Diabetes: A Propensity Score Analysis.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders. RESULTS: We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81-0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all). CONCLUSIONS: Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.

Securing the data economy: translating privacy and enacting security in the development of DataSHIELD.

Contemporary bioscience is seeing the emergence of a new data economy: with data as its fundamental unit of exchange. While sharing data within this new 'economy' provides many potential advantages, the sharing of individual data raises important social and ethical concerns. We examine ongoing development of one technology, DataSHIELD, which appears to elide privacy concerns about sharing data by enabling shared analysis while not actually sharing any individual-level data. We combine presentation of the development of DataSHIELD with presentation of an ethnographic study of a workshop to test the technology. DataSHIELD produced an application of the norm of privacy that was practical, flexible and operationalizable in researchers' everyday activities, and one which fulfilled the requirements of ethics committees. We demonstrated that an analysis run via DataSHIELD could precisely replicate results produced by a standard analysis where all data are physically pooled and analyzed together. In developing DataSHIELD, the ethical concept of privacy was transformed into an issue of security. Development of DataSHIELD was based on social practices as well as scientific and ethical motivations. Therefore, the 'success' of DataSHIELD would, likewise, be dependent on more than just the mathematics and the security of the technology.

Today's lifestyles, tomorrow's cancers: trends in lifestyle risk factors for cancer in low- and middle-income countries.

BACKGROUND: The global burden of cancer is projected to increase from 13.3 to 21.4 million incident cases between 2010 and 2030 due to demographic changes alone, dominated by a growing burden in low- and middle-income countries (LMICs). Lifestyle risk factors for cancer are also changing in these countries and may further influence this burden. DESIGN: We consider examples of changes already occurring in population-level distributions of tobacco and alcohol consumption, body weight, and reproductive lives of women to gauge the magnitude of their projected impact on cancer incidence in future decades. RESULTS: Trends in lifestyle factors vary greatly between settings and by sex. Some common trends point to considerable increases in cancers of the (i) lung in men due to tobacco smoking; (ii) upper aerodigestive tract (UADT) due to increasing tobacco and alcohol consumption, worse in men; (iii) colon from increasing body mass index, and alcohol and tobacco consumption; and (iv) in women, breast due particularly to consistent international trends of younger age at menarche, smaller family size, and, at postmenopausal ages, increasing body weight. CONCLUSIONS: In many LMICs, the future cancer burden will be worsened by changing lifestyles. Affected common cancer sites likely to experience the largest increases are lung, colon, UADT, and breast.

How much do smoking and alcohol consumption explain socioeconomic inequalities in head and neck cancer risk?

BACKGROUND: A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. METHODS: We conducted a case-control study in São Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. RESULTS: Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. CONCLUSIONS: Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.

Research on cancer prevention, detection and management in low- and medium-income countries.

The burden of cancer in low- and medium-income countries (LMIC) is expected to increase in the next decades. The application of current knowledge and results of research in key areas would contribute to limit the impact of this phenomenon. Opportunities for research on cancer prevention in LMIC include investigating specific circumstances of exposure to known carcinogens and to agents which are not prevalent in other regions, as well as interactions among carcinogens and between genetic and environmental factors. Early detection both by screening and early clinical diagnosis represents an important component of cancer control in LMIC. Research has been carried out to identify effective and sustainable approaches for early detection of cervical cancer through human papillomavirus testing and visual tests and of oral cancer through visual inspection. For other important neoplasms such as breast cancer, on the other hand, no effective low-cost screening methods are currently available. Downstaging represents a potentially important approach for cancer control and a priority area for future research. Studies addressing the efficacy of treatment protocols, country-specific cost-effectiveness of various interventions and the clinical utility and cost-effectiveness of innovative heath care and communication technologies represent the priority for clinical cancer research.

Exposure-response analysis and risk assessment for silica and silicosis mortality in a pooled analysis of six cohorts.

AIMS: To study the relation between exposure to crystalline silica and silicosis mortality. Although mortality is an important endpoint for regulators, there have been no exposure-response studies for silicosis mortality, because of the relative rareness of silicosis as an underlying cause of death, and the limited availability of quantitative exposure estimates. METHODS: Data from six occupational cohorts were pooled with good retrospective exposure data in which 170 deaths from silicosis were reported. Standard life table analyses, nested case-control analyses, and risk assessment were performed. RESULTS: The rate of silicosis mortality in the combined data was 28/100 000 py, increasing in nearly monotonic fashion from 4.7/100 000 for exposure of 0-0.99 mg/m(3)-years to 233/100 000 for exposure of >28.1 mg/m(3)-years. The estimated risk of death up to age 65 from silicosis after 45 years of exposure at 0.1 mg/m(3) silica (the current standard in many countries) was 13 per 1000, while the estimated risk at an exposure of 0.05 mg/m(3) was 6 per 1000. Both of these risks are above the risk of 1 per 1000 typically deemed acceptable by the US OSHA. CONCLUSION: The findings from this pooled analysis add further support to the need to control silica exposure and to lower the occupational standards. Our estimates of lifetime silicosis mortality risk are probably underestimates as, in addition to exposure misclassification, our study might have suffered from outcome misclassification in that silicosis deaths might have been coded to other related causes, such as tuberculosis or chronic obstructive pulmonary disease.

Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study.

OBJECTIVES: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. METHODS: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1,072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. RESULTS: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0. 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. CONCLUSIONS: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.

Lung cancer and cigarette smoking in Europe: an update of risk estimates and an assessment of inter-country heterogeneity.

Ten case-control studies have been carried out in 6 European countries to investigate the major risk factors for lung cancer. Carcinogenic effect from cigarette smoke was the most relevant interest in our study, which has included 7,609 cases of lung cancer and 10,431 controls, mainly population based. The results indicate elevated odds ratios (ORs; 23.9 among men and 8.7 among women) with attributable risks exceeding 90% for men and close to 60% for women. A large, and statistically significant, variability of the results across countries was detected after adjusting for the most common confounding variables, and after controlling, at least in part, for the instability of the ORs due to the small number of non-smokers in some of the study subsets. This pattern of lung cancer risk associated with cigarettes smoke, across different European regions, reflects inherent characteristics of the studies as well as differences in smoking habits, particularly calendar periods of starting, and it is likely to have been influenced by effect modifiers like indoor radon exposure, occupation, air pollution and dietary habits.

Occupational cancer in central European countries.

The countries of central Europe, including Poland, the Czech Republic, Slovakia, Hungary, Romania, and Bulgaria, suffer from environmental and occupational health problems created during the political system in place until the late 1980s. This situation is reflected by data on workplace exposure to hazardous agents. Such data have been systematically collected in Skovakia and the Czech Republic since 1977. The data presented describe mainly the situation in the early 1990s. The number of workers exposed to risk factors at the workplace represent about 10% of the working population in Slovakia and 30% in Poland. In Slovakia in 1992 the percentage of persons exposed to chemical substances was 16.4%, to ionizing radiation 4.3%, and to carcinogens 3.3% of all workers exposed to risk factors. The total number of persons exposed to substances proven to be carcinogens in Poland was 1.3% of the employees; 2.2% were exposed to the suspected carcinogens. The incidence of all certified occupational diseases in the Slovak Republic was 53 per 100,000 insured employees in 1992. Cancers certified as occupational cancers are skin cancer caused by occupational exposure to carcinogens, lung cancer caused by ionizing radiation, and asbestosis together with lung cancer. Specific information on occupational cancers from Romania and Bulgaria was not available for this paper. It is difficult to predict a trend for future incidences of occupational cancer. Improved control technology, governmental regulatory activity to reduce exposure, surveillance of diseases and risk factors, and vigilant use of preventive measures should, however, ultimately reduce occupational cancer.

Occupational cancer in the European part of the Commonwealth of Independent States.

Precise information on the number of workers currently exposed to carcinogens in the Commonwealth of Independent States (CIS) is lacking. However, the large number of workers employed in high-risk industries such as the chemical and metal industries suggests that the number of workers potentially exposed to carcinogens may be large. In the CIS, women account for almost 50% of the industrial work force. Although no precise data are available on the number of cancers caused by occupational exposures, indirect evidence suggests that the magnitude of the problem is comparable to that observed in Western Europe, representing some 20,000 cases per year. The large number of women employed in the past and at present in industries that create potential exposure to carcinogens is a special characteristic of the CIS. In recent years an increasing amount of high-quality research has been conducted on occupational cancer in the CIS; there is, however, room for further improvement. International training programs should be established, and funds from international research and development programs should be devoted to this area. In recent years, following privatization of many large-scale industries, access to employment and exposure data is becoming increasingly difficult.

Health effects of asbestos exposure in humans: a quantitative assessment.

Asbestos causes four diseases in humans: Lung fibrosis (asbestosis) follows heavy exposure and, in industrialized countries, is mainly a relic of past working conditions. The risk of pleural fibrosis and plaques is likely to be linearly dependent from time since first exposure and is present for all types of asbestos fibres. The diagnostic uncertainties regarding pleural plaques and the substantial degree of misclassification make it difficult to precisely estimate the shape of the dose-response relationship. The risk of lung cancer seems to be linearly related to cumulative asbestos exposure, with an estimated increase in risk of 1% for each fibre/ml-year of exposure. All fibre types seem to exert a similar effect on lung cancer risk; a multiplicative interaction with tobacco smoking has been suggested. Pleural mesothelioma is a malignant neoplasm which is specifically associated with asbestos exposure: the risk is linked with the cubic power of time since first exposure, after allowing for a latency period of 10 years, and depends on the fibre type, as the risk is about three times higher for amphiboles as compared to chrysotile. Environmental exposure to asbestos is also associated with mesothelioma risk.

Socioeconomic differences in cancer incidence and mortality.

This chapter summarizes accumulated data on the presence, magnitude and consistency of socioeconomic differentials in mortality and incidence of all malignant neoplasms and 24 individual types of neoplasms in 37 populations in 21 countries. More or less consistent excess risks in men in lower social strata were observed for all respiratory cancers (nose, larynx and lung) and cancers of the oral cavity and pharynx, oesophagus, stomach, and, with a number of exceptions, liver, as well as for all malignancies taken together. For women, low-class excesses were consistently encountered for cancers of the oesophagus, stomach, cervix uteri and, less consistently, liver. Men in higher social strata displayed excesses of colon and brain cancers and skin melanoma. In the two Latin American populations for which data were available, lung cancer was more frequent in higher social strata. Excesses in high female socioeconomic strata were seen in most populations for cancers of the colon, breast and ovary and for skin melanoma. Longitudinal data from England and Wales suggested widening over time of social class differences in men for all cancers combined and for cancers of the lung, larynx and stomach, and in women for all cancers combined and for cervical cancer.

Infection with Helicobacter pylori and parasites, social class and cancer.

Three genera of parasites are known or suspected risk factors for cancer in humans: Schistosoma, Opisthorchis and Clonorchis. No adequate information is available on the determinants of infections related to social class. Infection with the bacterium Helicobacter pylori is an important cause of stomach cancer. Studies, in particular from the United Kingdom and the United States of America, strongly suggest that social class factors, especially those acting during childhood, are determinants of the infection, with odds ratios of seroprevalence of the order of 1.5-5 for lower social class as compared with higher social class. A conservative estimate of the contribution of social class, acting through an increased prevalence of H. pylori infection, to the burden of stomach cancer gives a figure of over 50,000 stomach cancers per year worldwide, or 8% of all stomach cancers. In countries with both high and low prevalence of infection with H. pylori, it is likely that a sizeable proportion of this difference is due to social-class-related risk factors of infection.

Exposure to occupational carcinogens and social class differences in cancer occurrence.

It has been estimated that occupational exposures are responsible for about 4% of all human cancers in industrialized countries. These cancers are concentrated among manual workers and in the lower social classes, thus contributing to the social class gradient in cancer incidence and mortality. On the basis of the 1971 cancer mortality data from England and Wales, it was estimated that occupational cancer is responsible for about a third of the total cancer difference between high (I, II and III-NM) and low (III-M, IV and V) social classes, and for about half of the difference for lung and bladder cancer. However, direct evidence on the extent of the contribution of occupational exposure to carcinogens to social class differences is lacking, and several problems, such as the possible interaction between carcinogens and the effect of extraoccupational confounding factors, add further elements of uncertainty.

Environmental exposure, social class, and cancer risk.

Exposure to a variety of environmental factors associated with cancer occurrence varies by social class. These factors include air pollutants (SO2, NO2, total suspended particulates, etc.), toxic waste hazards, and ionizing and other radiation. Heavy environmental pollution has been associated with an increased risk of some cancers and in particular lung cancer. There is limited evidence suggesting that individuals from lower social classes are exposed to higher levels of environmental pollutants than are individuals from higher social classes. This may be due to the placement of new sources of pollution or of toxic processes in disadvantaged areas, or to the selective migration of the poorer sectors of society to these areas. The available data do not allow any conclusion on the possible contribution of exposure to environmental pollution to social class differences in cancer occurrence. Exposure to ultraviolet (UV) radiation, principally from sunlight, is modified strongly by personal behaviours such as choice of recreation and use of protective clothing. Those in outdoor occupations are likely to receive the highest cumulative exposure to UV radiation. There is no clear evidence from recent survey research in Australia and North America that socioeconomic factors are strongly related to non-occupational exposure to UV radiation. Information is lacking on the influence of socioeconomic status on sun exposure in other parts of the world. There is little information on the social distribution of exposure to ionizing radiation.

A cohort study of workers compensated for mercury intoxication following employment in the fur hat industry.

This article presents the preliminary results of a follow-up study (1950-1992) of 1,146 subjects (person-years = 30,954; 23,055 for women) receiving compensation for mercury poisoning. In a province of Tuscany in central Italy, severe exposure to mercury occurred during fur hat production. A deficit in all causes of mortality was observed in both sexes, whereas mortality due to cancer was slightly higher than expected. Mortality from stomach cancer was significantly elevated for men and women. A significant excess of lung cancer was observed in women only. Whereas the excess of stomach cancer probably reflects elevated rates in the study area rather than exposure to mercury, the excess of lung cancer mortality does appear to be related to mercury exposure. Smoking habits or other exposures at work do not seem to explain the excess of lung cancer.

[Influence of sociodemographic variables in the enrollment of subjects in a population case-control study]. / Influenza di variabili sociodemografiche nel reclutamento dei soggetti in uno studio caso-controllo di popolazione.

Selection in representation of the study base was quantified in a case-control study of laryngeal cancer among residents of the City of Torino, Italy. Two-hundred-ninety-nine out of 408 eligible cases (73.3%) and 608 out of 1104 (55.1%) eligible controls were interviewed. All interviewed and non interviewed subjects were compared in a logistic regression model with respect to age, sex, educational level, civil status and area of birth. No large differential selection with respect to these variables was found between interviewed and non interviewed cases. Lower proportions of interviewed subjects were found among older controls and controls with lower education. These results suggest the possibility of selection bias in this case-control study. In particular, biased measures of effects might be estimated when analyzing variables related to educational level.