Cancer rates not explained by smoking: a county-level analysis.

BACKGROUND: Debates over the importance of "lifestyle" versus "environment" contributions to cancer have been going on for over 40 years. While it is clear that cigarette smoking is the most significant cancer risk factor, the contributions of occupational and environmental carcinogens in air, water and food remain controversial. In practice, most cancer prevention messaging focuses on reducing cigarette smoking and changing other personal behaviors with little mention of environmental chemicals, despite widespread exposure to many known carcinogens. To inform decision-making on cancer prevention priorities, we evaluated the potential impact of smoking cessation on cancer rates. METHODS: Using cancer incidence data from 612 counties in the SEER database, and county-level smoking prevalences, we investigated the impact of smoking cessation on incidence for 12 smoking-related cancer types, 2006-2016. A multilevel mixed-effects regression model quantified the association between county-level smoking prevalence and cancer incidence, adjusting for age, gender and variability over time and among counties. We simulated complete smoking cessation and estimated the effects on county-level cancer rates. RESULTS: Regression models showed the expected strong association between smoking prevalence and cancer incidence. Simulating complete smoking cessation, the incidence of the 12 smoking-related cancer types fell by 39.8% (54.9% for airways cancers; 28.9% for non-airways cancers). And, while the actual rates of smoking-related cancers from 2006 to 2016 declined (annual percent change (APC) = - 0.8, 95% CI = - 1.0 to - 0.5%), under the scenario of smoking elimination, the trend in cancer incidence at these sites was not declining (APC = - 0.1, 95% CI = - 0.4 to + 0.1%). Not all counties were predicted to benefit equally from smoking elimination, and cancer rates would fall less than 10% in some counties. CONCLUSIONS: Smoking prevention has produced dramatic reductions in cancer in the US for 12 major types. However, we estimate that eliminating smoking completely would not affect about 60% of cancer cases of the 12 smoking-related types, leaving no improvement in the incidence trend from 2006 to 2016. We conclude that cancer prevention strategies should focus not only on lifestyle changes but also the likely contributions of the full range of risk factors, including environmental/occupational carcinogens.

Post-Vietnam military herbicide exposures in UC-123 Agent Orange spray aircraft.

BACKGROUND: During the Vietnam War, approximately 20 million gallons of herbicides, including ~10.5 million gallons of dioxin-contaminated Agent Orange, were sprayed by about 34 UC-123 aircraft that were subsequently returned to the United States, without decontamination or testing, to three Air Force reserve units for transport operations (~1971-1982). In 1996, observed dioxin contamination led to withdrawal of these UC-123s from public auction and to their smelting in 2009. Current Air Force and Department of Veterans Affairs policies stipulate that "dried residues" of chemical herbicides and dioxin had not lead to meaningful exposures to flight crew and maintenance personnel, who are thus ineligible for Agent Orange-related benefits or medical examinations and treatment. Sparse monitoring data are available for analysis. METHODS: Three complementary approaches for modeling potential exposures to dioxin in the post-Vietnam war aircraft were employed: (1) using 1994 and 2009 Air Force surface wipe data to model personnel exposures and to estimate dioxin body burden for dermal-oral exposure for dried residues using modified generic US Environmental Protection Agency intake algorithms; (2) comparing 1979 Air Force 2,4- dichlorophenoxyacetic acid and 2,4-5-trichlorophenoxyacetic acid air samples to saturated vapor pressure concentrations to estimate potential dioxin exposure through inhalation, ingestion and skin contact with contaminated air and dust; and (3) applying emission models for semivolatile organic compounds from contaminated surfaces to estimate airborne contamination. RESULTS: Model (1): Body-burden estimates for dermal-oral exposure were 0.92 and 5.4pg/kg body-weight-day for flight crew and maintainers. The surface wipe concentrations were nearly two orders of magnitude greater than the US Army guidance level. Model (2): measured airborne concentrations were at least five times greater than saturated vapor pressure, yielding dioxin estimates that ranged from 13.2-27.0pg/m(3), thus supporting the likelihood of dioxin dust adsorption. Model (3): Theoretical models yielded consistent estimates to Model 2, 11-49pg/m(3), where the range reflects differences in experimental value of dioxin vapor pressure and surface area used. Model (3) results also support airborne contamination and dioxin dust adsorption. CONCLUSIONS: Inhalation, ingestion and skin absorption in aircrew and maintainers were likely to have occurred during post-Vietnam use of the aircraft based on the use of three complementary models. Measured and modeled values for dioxin exceeded several available guidelines. Deposition-aerosolization-redeposition homeostasis of semivolatile organic compound contaminants, particularly dioxin, is likely to have continually existed within the aircraft. Current Air Force and Department of Veterans Affairs policies are not consistent with the available industrial hygiene measurements or with the widely accepted models for semivolatile organic compounds.

Mesothelioma and employment in massachusetts: analysis of cancer registry data 1988-2003.

BACKGROUND: Cancer registries can be used to monitor mesothelioma cases and to identify occupations and industries previously and newly associated with mesothelioma-causing asbestos exposure by using standard registry data on the "usual" occupation and industry of the case. METHODS: We used the National Institute for Occupational Safety and Health's Standardized Occupational Industry Coding Software to code 564 mesothelioma cases for occupation and 543 for industry of the 1,424 incident mesothelioma in the Massachusetts Cancer Registry from 1988 to 2003. Additionally, we coded the occupation and industry of 80,184 comparison cancer cases (35% of comparison cases in our database). These were used to compute Standardized Morbidity Odds Ratios (SMORs). RESULTS: Seventeen occupations and 11 industries had statistically significant elevated SMORs for mesothelioma. Occupations and industries historically associated with mesothelioma remained elevated in these results. However, we also found statistically significant elevated SMORs for several occupations and industries for which there was previously weak or no association such as chemical engineers, machine operators, and automobile mechanics and machine manufacturing, railroads, and the U.S. Postal Service. CONCLUSIONS: Incident cases of mesothelioma do not appear to be declining in Massachusetts, as legacy exposures to asbestos continue to produce cases in individuals involved in shipbuilding and construction. Exposures in occupations and industries not previously associated with mesothelioma also contribute cases. Cancer registries, with improved data collection, should continue to be monitored for mesothelioma cases and asbestos exposures.

A retrospective cohort study of lung cancer incidence in nylon flock workers, 1998-2008.

During an investigation of a novel interstitial lung disease in a cohort of nylon flock workers, a former worker was found to have developed bilateral synchronous pulmonary adenocarcinomas three decades after he quit smoking, suggesting that exposures in this industry might pose excessive risk of lung cancer. We conducted a retrospective cohort study of lung cancer incidence in the original study cohort (n=162) from August 15, 1998, to August 14, 2008. The Rhode Island Cancer Registry identified cohort members with lung cancer and provided age-gender-era-specific rates of lung cancer in Rhode Island. Five cases of lung cancer occurred among cohort members versus 1.61 cases expected for a standardized incidence ratio of 3.1 (95% CI, 1.01-7.23). The observed threefold increase in lung cancer incidence could not be readily ascribed to chance, study bias, or uncontrolled confounding. Workers in this industry should be notified of their potentially increased risk of lung cancer.

Cancer mortality in IBM Endicott plant workers, 1969-2001: an update on a NY production plant.

BACKGROUND: In response to concerns expressed by workers at a public meeting, we analyzed the mortality experience of workers who were employed at the IBM plant in Endicott, New York and died between 1969-2001. An epidemiologic feasibility assessment indicated potential worker exposure to several known and suspected carcinogens at this plant. METHODS: We used the mortality and work history files produced under a court order and used in a previous mortality analysis. Using publicly available data for the state of New York as a standard of comparison, we conducted proportional cancer mortality (PCMR) analysis. RESULTS: The results showed significantly increased mortality due to melanoma (PCMR = 367; 95% CI: 119, 856) and lymphoma (PCMR = 220; 95% CI: 101, 419) in males and modestly increased mortality due to kidney cancer (PCMR = 165; 95% CI: 45, 421) and brain cancer (PCMR = 190; 95% CI: 52, 485) in males and breast cancer (PCMR = 126; 95% CI: 34, 321) in females. CONCLUSION: These results are similar to results from a previous IBM mortality study and support the need for a full cohort mortality analysis such as the one being planned by the National Institute for Occupational Safety and Health.

Environmental and occupational causes of cancer: new evidence 2005-2007.

What do we currently know about the occupational and environmental causes of cancer? As of 2007, the International Agency for Research on Cancer (IARC) identified 415 known or suspected carcinogens. Cancer arises through an extremely complicated web of multiple causes, and we will likely never know the full range of agents or combinations of agents. We do know that preventing exposure to individual carcinogens prevents the disease. Declines in cancer rates-such as the drop in male lung cancer cases from the reduction in tobacco smoking or the drop in bladder cancer among cohorts of dye workers from the elimination of exposure to specific aromatic amines-provides evidence that preventing cancer is possible when we act on what we know. Although the overall age-adjusted cancer incidence rates in the United States among both men and women have declined in the last decade, the rates of several types of cancers are on the rise; some of which are linked to environmental and occupational exposures. This report chronicles the most recent epidemiologic evidence linking occupational and environmental exposures with cancer. Peer-reviewed scientific studies published from January 2005 to June 2007 were reviewed, supplementing our state-of-the-evidence report published in September 2005. Despite weaknesses in certain individual studies, we consider the evidence linking the increased risk of several types of cancer with specific exposures somewhat strengthened by recent publications, among them brain cancer from exposure to non-ionizing radiation, particularly radiofrequency fields emitted by mobile telephones; breast cancer from exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) before puberty; leukemia from exposure to 1,3-butadiene; lung cancer from exposure to air pollution; non-Hodgkin's lymphoma (NHL) from exposure to pesticides and solvents; and prostate cancer from exposure to pesticides, polyaromatic hydrocarbons (PAHs), and metal working fluids or mineral oils. In addition to NHL and prostate cancer, early findings from the National Institutes of Health Agricultural Health Study suggest that several additional cancers may be linked to a variety of pesticides. Our report also briefly describes the toxicological evidence related to the carcinogenic effect of specific chemicals and mechanisms that are difficult to study in humans, namely exposures to bis-phenol A and epigenetic, trans-generational effects. To underscore the multi-factorial, multi-stage nature of cancer, we also present a technical description of cancer causation summarizing current knowledge in molecular biology. We argue for a new cancer prevention paradigm, one based on an understanding that cancer is ultimately caused by multiple interacting factors rather than a paradigm based on dubious attributable fractions. This new cancer prevention paradigm demands that we limit exposure to avoidable environmental and occupational carcinogens, in combination with additional important risk factors like diet and lifestyle. The research literature related to environmental and occupational causes of cancer is constantly growing, and future updates will be carried out in light of new biological understanding of the mechanisms and new methods for studying exposures in human populations. The current state of knowledge is sufficient to compel us to act on what we know. We repeat the call of ecologist Sandra Steingraber: "From the right to know and the duty to inquire flows the obligation to act."

Environmental and occupational causes of cancer: a call to act on what we know.

The discussion of the scientific evidence linking cancer to environmental and occupational exposures has been an area of contention for atleast the past three decades, since the assertion in 1977 by Higginson and Muir that 80% of all cancers were due to environmental exposures. Over the past three decades, there have been additional efforts to estimate the proportion of cancer due to these involuntary exposures, including the 1981 monograph by Doll and Peto and the more recent reports by the Harvard Center for Cancer Prevention. In this paper, we review the evidence that Doll and Peto and other authors have summarized, provide an alternative interpretation of the evidence, and caution against the very idea of attributing specific fractions or proportions of cancer to particular factors. We also review the scientific evidence, particularly epidemiologic evidence, regarding the contribution of environmental and occupational exposures to the overall cancer burden in the US. We conclude with a call for action to prevent exposures to environmental and occupational carcinogens.

The increasing toll of adolescent cancer incidence in the US.

Cancer incidence is rising among adolescents ("teens"). The causes of the increase are unknown but studying incidence patterns and trends may produce insights into etiology. Using data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program we described trends of cancer incidence among teens (15-19 year olds). We reviewed and summarized incidence patterns for histologic cancer groups and the most frequently diagnosed sites of cancer among teens during 2008-2012 reported by the SEER Cancer Statistics Review. We calculated annual incidence rates for the years 1975-2012 and used linear regression analysis to evaluate trends and calculate rates of change. Incidence for all sites combined increased annually by 0.67% for males and 0.62% for females during the period 1975 through 2012 -resulting in more than a 25% increase over 38 years. The biggest annual incidence increases occurred in non-Hodgkin lymphoma (NHL) (2.16% females; 1.38% males), thyroid cancer (2.12% females; 1.59% males), acute myeloid leukemia (AML) (1.73% females) and testicular cancer (1.55% males). Incidence rates for most histologic groups and sites showed steady long term increases over the 38 years of data. Despite improvements in survival, rising incidence trends mean growing numbers of young adults are undergoing painful and costly cancer treatments. A concerted research program is vital to investigate causes of steadily rising teen cancer rates.

Environmental and occupational causes of cancer re-visited.

We recently completed a review of scientific evidence, particularly epidemiologic evidence, regarding the contribution of environmental and occupational exposures to the overall cancer burden in the US. We evaluated the efforts to estimate the proportion of cancer due to these involuntary exposures, including the ambitious effort by Doll and Peto and an update by a group of authors at the Harvard Center for Cancer Prevention. In this paper, we critique these efforts, and their resulting estimates of the proportion of cancer due to various factors. We also provide an alternative interpretation of the evidence and a caution against the very idea of attributing specific fractions or proportions of cancer to particular factors. We conclude by recommending that environmental and occupational links to cancer be given serious consideration by individuals and institutions concerned with cancer prevention, particularly those involved in research and public education. We support the new initiative in the European Union to evaluate chemicals more fully before they reach the market.

Mortality among US employees of a large computer manufacturing company: 1969-2001.

BACKGROUND: Previous studies suggested increased cancer incidence and mortality in workers exposed to solvents and other chemicals in computer manufacturing jobs. Most previous studies were of small cohorts and findings were inconsistent. A lawsuit involving a large U.S. company produced a data file for analysis. This study sought to elucidate patterns of mortality in workers who were engaged manufacturing computers and related electronic components in the largest database available to date. METHODS: A proportional mortality and proportional cancer mortality analysis of deaths in eligible workers between 1969 and 2001 was carried out, with U.S. population mortality data as the standard for comparison. Mortality and work history data was from corporate mortality and work history files produced during litigation and standard U.S. and state mortality files. The study base comprised 31,941 decedents who died between 1969 and 2001, who had worked for at least five years and whose death information was collected in the corporate mortality file. Proportional mortality ratios (PMRs) and Proportional Cancer Mortality Ratios (PCMRs) and their 95% confidence intervals were computed for 66 causes of death in males and females. RESULTS: PMRs for all cancers combined were elevated in males (PMR = 107; 95% CI = 105-109) and females (PMR = 115; 95% CI = 110-119); several specific cancers and other causes of death were also significantly elevated in both males and females. There were reduced deaths due to non-malignant respiratory disease in males and females and heart disease in females; several specific cancers and other causes of death were significantly reduced in both males and females. Proportional cancer mortality ratios (PCMRs) for brain and central nervous system cancer were elevated (PCMR = 166; 95% CI = 129-213), kidney cancer (PCMR = 162; 95% CI = 124-212), melanoma of skin (PCMR = 179; 95% CI = 131-244) and pancreatic cancer (PCMR = 126; 95% CI = 101-157) were significantly elevated in male manufacturing workers. Kidney cancer (PCMR = 212; 95% CI = 116-387) and cancer of all lymphatic and hematopoietic tissue (PCMR = 162; 95% CI = 121-218) were significantly elevated in female manufacturing workers. CONCLUSION: Mortality was elevated due to specific cancers and among workers more likely to be exposed to solvents and other chemical exposures in manufacturing operations. Due to lack of individual exposure information, no conclusions are made about associations with any particular agent.

Environmental and Economic Strategies for Primary Prevention of Cancer in Early Life.

This article summarizes the evidence for environmental toxic exposures contributing to cancers in early life, focusing on the most common cancer sites in this age group. It provides examples of widespread avoidable exposures to human carcinogens through air, water, and food and then describes recent examples of successful initiatives to reduce exposure to chemicals linked to these cancer sites, through government policy, industry initiatives, and consumer activism. State government initiatives to reduce toxic chemical exposures have made important gains; the Toxics Use Reduction Act of Massachusetts is now 25 years old and has been a major success story. There are a growing number of corporate initiatives to eliminate toxics, especially carcinogens, from the products they manufacture and sell. Another important opportunity for cancer prevention is provided by online databases that list chemicals, their toxicity, and lower-toxicity alternatives; these can be used by businesses, health care institutions, consumers, and workers to reduce exposures to chemicals of concern. The article concludes by inviting pediatricians and public health professionals to include elimination of carcinogen exposures in their work to promote primary prevention of cancer in early life.

Perfluorinated Alkyl Substances: Emerging Insights Into Health Risks.

Perfluorinated alkyl substances have been in use for over sixty years. These highly stable substances were at first thought to be virtually inert and of low toxicity. Toxicity information slowly emerged on perfluorooctanoic acid and perfluorooctane sulfonate. More than thirty years ago, early studies reported immunotoxicity and carcinogenicity effects. The substances were discovered in blood samples from exposed workers, then in the general population and in community water supplies near U.S. manufacturing plants. Only recently has research publication on perfluorooctanoic acid and perfluorooctane sulfonate intensified. While the toxicology database is still far from complete, carcinogenicity and immunotoxicity now appear to be relevant risks at prevalent exposure levels. Existing drinking water limits are based on less complete evidence that was available before 2008 and may be more than 100-fold too high. As risk evaluations assume that untested effects do not require regulatory attention, the greatly underestimated health risks from perfluorooctanoic acid and perfluorooctane sulfonate illustrate the public health implications of assuming the safety of incompletely tested industrial chemicals.