Statistical modeling and projections of lung cancer mortality in 4 industrialized countries

The purpose of this work was to model lung cancer mortality as a function of past exposure to tobacco and to forecast age-sex-specific lung cancer mortality rates. A 3-factor age-period-cohort (APC) model, in which the period variable is replaced by the product of average tar content and adult tobacco consumption per capita, was estimated for the US, UK, Canada and Australia by the maximum likelihood method. Age- and sex-specific tobacco consumption was estimated from historical data on smoking prevalence and total tobacco consumption. Lung cancer mortality was derived from vital registration records. Future tobacco consumption, tar content and the cohort parameter were projected by autoregressive moving average (ARIMA) estimation. The optimal exposure variable was found to be the product of average tar content and adult cigarette consumption per capita, lagged for 2530 years for both males and females in all 4 countries. The coefficient of the product of average tar content and tobacco consumption per capita differs by age and sex. In all models, there was a statistically significant difference in the coefficient of the period variable by sex. In all countries, male age-standardized lung cancer mortality rates peaked in the 1980s and declined thereafter. Female mortality rates are projected to peak in the first decade of this century. The multiplicative models of age, tobacco exposure and cohort fit the observed data between 1950 and 1999 reasonably well, and time-series models yield plausible past trends of relevant variables. Despite a significant reduction in tobacco consumption and average tar content of cigarettes sold over the past few decades, the effect on lung cancer mortality is affected by the time lag between exposure and established disease. As a result, the burden of lung cancer among females is only just reaching, or soon will reach, its peak but has been declining for I to 2 decades in men. Future sex differences in lung cancer mortality are likely to be greater in North America than Australia and the UK due to differences in exposure patterns between the sexes. (c) 2005 Wiley-Liss, Inc.

Regional, disease specific patterns of smoking-attributable mortality in 2000

Background: Smoking has been causally associated with increased mortality from several diseases, and has increased considerably in many developing countries in the past few decades. Mortality attributable to smoking in the year 2000 was estimated for adult males and females, including estimates by age and for specific diseases in 14 epidemiological subregions of the world. Methods: Lung cancer mortality was used as an indirect marker of the accumulated hazard of smoking. Never-smoker lung cancer mortality was estimated based on the household use of coal with poor ventilation. Estimates of mortality caused by smoking were made for lung cancer, upper aerodigestive cancer, all other cancers, chronic obstructive pulmonary disease ( COPD), other respiratory diseases, cardiovascular diseases, and selected other medical causes. Estimates were limited to ages 30 years and above. Results: In 2000, an estimated 4.83 million premature deaths in the world were attributable to smoking, 2.41 million in developing countries and 2.43 million in industrialised countries. There were 3.84 million male deaths and 1.00 million female deaths attributable to smoking. 2.69 million smoking attributable deaths were between the ages of 30 - 69 years, and 2.14 million were 70 years of age and above. The leading causes of death from smoking in industrialised regions were cardiovascular diseases ( 1.02 million deaths), lung cancer (0.52 million deaths), and COPD (0.31 million deaths), and in the developing world cardiovascular diseases (0.67 million deaths), COPD (0.65 million deaths), and lung cancer (0.33 million deaths). The share of male and female deaths and younger and older adult deaths, and of various diseases in total smoking attributable deaths exhibited large inter-regional heterogeneity, especially in the developing world. Conclusions: Smoking was an important cause of global mortality in 2000, affecting a large number of diseases. Age, sex, and disease patterns of smoking-caused mortality varied greatly across regions, due to both historical and current smoking patterns, and the presence of other risk factors that affect background mortality from specific diseases.

Role of smoking in global and regional cancer epidemiology: current patterns and data needs

Although smoking is widely recognized as a major cause of cancer, there is little information on how it contributes to the global and regional burden of cancers in combination with other risk factors that affect background cancer mortality patterns. We used data from the American Cancer Society's Cancer Prevention Study II (CPS-II) and the WHO and IARC cancer mortality databases to estimate deaths from 8 clusters of site-specific cancers caused by smoking, for 14 epidemiologic subregions of the world, by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.42 (95% CI 1.27-1.57) million cancer deaths in the world, 21% of total global cancer deaths, were caused by smoking. Of these, 1.18 million deaths were among men and 0.24 million among women; 625,000 (95% CI 485,000-749,000) smoking-caused cancer deaths occurred in the developing world and 794,000 (95% CI 749,000-840,000) in industrialized regions. Lung cancer accounted for 60% of smoking-attributable cancer mortality, followed by cancers of the upper aerodigestive tract (20%). Based on available data, more than one in every 5 cancer deaths in the world in the year 2000 were caused by smoking, making it possibly the single largest preventable cause of cancer mortality. There was significant variability across regions in the role of smoking as a cause of the different site-specific cancers. This variability illustrates the importance of coupling research and surveillance of smoking with that for other risk factors for more effective cancer prevention. (C) 2005 Wiley-Liss, Inc.

Role of smoking in global and regional cardiovascular mortality

Background - Smoking is a major cause of cardiovascular disease mortality. There is little information on how it contributes to global and regional cause-specific mortality from cardiovascular diseases for which background risk varies because of other risks. Method and Results - We used data from the American Cancer Society's Cancer Prevention Study II (CPS II) and the World Health Organization Global Burden of Disease mortality database to estimate smoking-attributable deaths from ischemic heart disease, cerebrovascular disease, and a cluster of other cardiovascular diseases for 14 epidemiological subregions of the world by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.62 (95% CI, 1.27 to 2.04) million cardiovascular deaths in the world, 11% of total global cardiovascular deaths, were due to smoking. Of these, 1.17 million deaths were among men and 450 000 among women. There were 670 000 (95% CI, 440 000 to 920 000) smoking-attributable cardiovascular deaths in the developing world and 960 000 (95% CI, 770 000 to 1 200 000) in industrialized regions. Ischemic heart disease accounted for 54% of smoking-attributable cardiovascular mortality, followed by cerebrovascular disease (25%). There was variability across regions in the role of smoking as a cause of various cardiovascular diseases. Conclusions - More than 1 in every 10 cardiovascular deaths in the world in the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality.

Social inequalities in male mortality, and in male mortality from smoking: indirect estimation from national death rates in England and Wales, Poland, and North America

Background There are substantial social inequalities in adult male mortality in many countries. Smoking is often more prevalent among men of lower social class, education, or income. The contribution of smoking to these social inequalities in mortality remains uncertain. Methods The contribution of smoking to adult mortality in a population can be estimated indirectly from disease-specific death rates in that population (using absolute lung cancer rates to indicate proportions due to smoking of mortality from certain other diseases). We applied these methods to 1996 death rates at ages 35-69 years in men in three different social strata in four countries, based on a total of 0.6 million deaths. The highest and lowest social strata were based on social class (professional vs unskilled manual) in England and Wales, neighbourhood income (top vs bottom quintile) in urban Canada, and completed years of education (more than vs less than 12 years) in the USA and Poland. Results In each country, there was about a two-fold difference between the highest and the lowest social strata in overall risks of dying among men aged 35-69 years (England and Wales 21% vs 43%, USA 20% vs 37%, Canada 21% vs 34%, Poland 26% vs 50%: four-country mean 22% vs 41%, four-country mean absolute difference 19%). More than half of this difference in mortality between the top and bottom social strata involved differences in risks of being killed at age 35-69 years by smoking (England and Wales 4% vs 19%, USA 4% vs 15%, Canada 6% vs 13%, Poland 5% vs 22%: four-country mean 5% vs 17%, four-country mean absolute difference 12%). Smoking-attributed mortality accounted for nearly half of total male mortality in the lowest social stratum of each country. Conclusion In these populations, most, but not all, of the substantial social inequalities in adult male mortality during the 1990s were due to the effects of smoking. Widespread cessation of smoking could eventually halve the absolute differences between these social strata in the risk of premature death.

Searching for cancer deaths in Australia: National Death Index vs Cancer Registries

OBJECTIVE: To compare the accuracy, costs and utility of using the National Death Index (NDI) and state-based cancer registries in determining the mortality status of a cohort of women diagnosed with ovarian cancer in the early 1990s. METHODS: As part of a large prognostic study, identifying information on 822 women diagnosed with ovarian cancer between 1990 and 1993, was simultaneously submitted to the NDI and three state-based cancer registries to identify deceased women as of June 30, 1999. This was compared to the gold standard of "definite deaths". A comparative evaluation was also made of the time and costs associated with the two methods. RESULTS: Of the 450 definite deaths in our cohort the NDI correctly identified 417 and all of the 372 women known to be alive (sensitivity 93%, specificity 100%). Inconsistencies in identifiers recorded in our cohort files, particularly names, were responsible for the majority of known deaths not matching with the NDI, and if eliminated would increase the sensitivity to 98%. The cancer registries correctly identified 431 of the 450 definite deaths (sensitivity 96%). The costs associated with the NDI search were the same as the cancer registry searches, but the cancer registries took two months longer to conduct the searches. CONCLUSIONS AND IMPLICATIONS: This study indicates that the cancer registries are valuable, cost effective agencies for follow-up of mortality outcome in cancer cohorts, particularly where cohort members were residents of those states. For following large national cohorts the NDI provides additional information and flexibility when searching for deaths in Australia. This study also shows that women can be followed up for mortality with a high degree of accuracy using either service. Because each service makes a valuable contribution to the identification of deceased cancer subjects, both should be considered for optimal mortality follow-up in studies of cancer patients.

Chronic obstructive pulmonary disease: current burden and future projections

Information about the comparative magnitude of the burden from various diseases and injuries is a critical input into building the evidence base for health policies and programmes. Such information should be based on a critical evaluation of all available epidemiological data using standard and comparable procedures across diseases and injuries, including information on the age at death and the incidence, duration and severity of cases who do not die prematurely from the disease. A summary measure, disability-adjusted life yrs (DALYs), has been developed to simultaneously measure the amount of disease burden due to premature mortality and the amount due to the nonfatal consequences of disease.

Changes in survival after breast cancer: improvements in diagnosis or treatment?

We have compared 5-year survival rates in two cohorts of women diagnosed with breast cancer in Brisbane, Australia, between 1981-1984 and 1990-1994. Tumours diagnosed in the early 1990s were significantly smaller and less likely to have nodal involvement than those diagnosed 10 years earlier (P < 0.0001). The size difference was particularly striking for women aged over 50 at diagnosis, those targeted for screening. Five-year survival was greater among women diagnosed in the 1990s (84% vs. 74%; hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.81). After adjusting for the effects of tumour size and nodal status this difference was reduced, but women diagnosed more recently still showed improved survival (HR 0.75; 95% CI 0.56-1.01) and disease-free survival (HR 0.72; 0.56-0.92) at 5 years. This suggests that both earlier diagnosis and changes in breast cancer treatment have contributed to improved breast cancer survival. (C) 2003 Elsevier Ltd. All rights reserved.

Molecular introduction to head and neck cancer (HNSCC) carcinogenesis

Of all human cancers, HNSCC is the most distressing affecting pain, disfigurement, speech and the basic survival functions of breathing and swallowing. Mortality rates have not significantly changed in the last 40 years despite advances in radiotherapy and surgical treatment. Molecular markers are currently being identified that can determine prognosis preoperatively by routine tumour biopsy Leading to improved management of HNSCC patients. The approach could help decide which early stage patient should have adjuvant neck dissection and radiotherapy, and whether Later stage patients with operable lesions would benefit from resection and reconstructive surgery or adopt a conservative approach to patients with poor prognosis regardless of treatment. In the future, understanding these basic genetic changes in HNSCC would be important for the management of HNSCC. (C) 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

Colorectal cancer screening in Australia: an economic evaluation of a potential biennial screening program using faecal occult blood tests

Objective: To evaluate whether the introduction of a national, co-ordinated screening program using the faecal occult blood test represents 'value-for-money' from the perspective of the Australian Government as third-party funder. Methods: The annual equivalent costs and consequences of a biennial screening program in 'steady-state' operation were estimated for the Australian population using 1996 as the reference year. Disability-adjusted life years (DALYs) and the years of life lost (YLLs) averted, and the health service costs were modelled, based on the epidemiology and the costs of colorectal cancer in Australia together with the mortality reduction achieved in randomised controlled trials. Uncertainty in the model was examined using Monte Carlo simulation methods. Results: We estimate a minimum or 'base program' of screening those aged 55 to 69 years could avert 250 deaths per annum (95% uncertainty interval 99-400), at a gross cost of $A55 million (95% UI $A46 million to $A96 million) and a gross incremental cost-effectiveness ratio of $A17,000/DALY (95% UI $A13,000/DALY to $A52,000/DALY). Extending the program to include 70 to 74-year-olds is a more effective option (cheaper and higher health gain) than including the 50 to 54-year-olds. Conclusions: The findings of this study support the case for a national program directed at the 55 to 69-year-old age group with extension to 70 to 74-year-olds if there are sufficient resources. The pilot tests recently announced in Australia provide an important opportunity to consider the age range for screening and the sources of uncertainty, identified in the modelled evaluation, to assist decisions on implementing a full national program.

Lung cancer rates in men and women with comparable histories of smoking

Background: Recent case-control studies suggest that, given equal smoking exposure, women may have a higher relative risk of developing lung cancer than men. Despite prospective data that conflict with this hypothesis, mechanistic studies to find a biologic basis for a sex difference continue. Methods: We addressed the hypothesis directly by analyzing prospective data from former and current smokers in two large cohorts-the Nurses' Health Study of women and the Health Professionals Follow-up Study of men. We calculated incidence rates and hazard ratios of lung cancer in women compared with men, adjusting for age, number of cigarettes smoked per day, age at start of smoking, and time since quitting, using Cox proportional hazards models. We also reviewed published results from prospective analyses. Results: From 1986 through 2000, 955 and 311 primary lung cancers were identified among 60 296 women and 25 397 men, respectively, who ranged in age from 40 to 79 years. Incidence rates per 100 000 person-years for women and men were 253 and 232, respectively, among current smokers and 81 and 73, respectively, among former smokers. The hazard ratio in women ever smokers compared with men was 1.11 (95% confidence interval = 0.95 to 1.31). Six published prospective cohort studies allowed assessment of comparative susceptibility to lung cancer by sex. None supported an excess risk of lung cancer for women. Conclusions: Women do not appear to have a greater susceptibility to lung cancer than men, given equal smoking exposure. Research should be focused on enhancing preventive interventions for all.

Prevalence of whole-body skin self-examination in a population at high risk for skin cancer (Australia)

Objective: Whole-body skin self-examination (SSE) with presentation of suspicious lesions to a physician may improve early detection of melanoma. The aim of this study was to establish the prevalence and determinants of SSE in a high-risk population in preparation for a community-based randomised controlled trial of screening for melanoma. Methods: A telephone survey reached 3110 residents older than 30 years (overall response rate of 66.9%) randomly selected from 18 regional communities in Queensland, Australia. Results: Overall, 804 (25.9%) participants reported whole-body SSE within the past 12 months and 1055 (33.9%) within the past three years. Whole-body SSE was associated in multivariate logistic regression analysis with younger age (< 50 years); higher education; having received either a whole-body skin examination, recommendation or instruction on SSE by a primary care physician; giving skin checks a high priority; concern about skin cancer and a personal history of skin cancer. Conclusion: Overall, the prevalence of SSE in the present study is among the highest yet observed in Australia, with about one-third of the adult population reporting whole-body SSE in the past three years. People over 50 years, who are at relatively higher risk for skin cancer, currently perform SSE less frequently than younger people.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former east-Germany

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1%) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.