Lung Cancer Other Achievements: Highlights

What is the effect of tobacco control programs on reducing smoking prevalence and tobacco-related mortality?

The CISNET lung model (SimSmoke) developed by the Georgetown University group can be used to retrospectively estimate the impact of various tobacco control policies on observed declines in smoking rates and on tobacco-related mortality, as well as to project the potential impact of tobacco control policies on reducing these rates. The model has been applied to estimate effects at the state and national levels:

Results consistently showed that cigarette price increases and educational media campaigns had the largest impact on smoking rates, with substantially smaller effects attributable to telephone quit lines, youth access policies, and clean air laws. Models of this type can assist policy makers at the state and national levels by demonstrating tobacco control progress in specific states, explaining the policies that have contributed to declines in smoking prevalence, and determining the potential impact of enhanced tobacco control efforts in other regions of the country.

The CISNET smoking population model was used to estimate the impact of tobacco control on overall mortality in the US since the publication of the 1964 Surgeon General’s report (SGR) (Holford, Meza et al. 2014). Counterfactual scenarios were first developed projecting smoking prevalence in the absence of tobacco control from 1964 forward. The model estimated that approximately 8 million premature deaths were prevented by tobacco control in the US since 1964, resulting in an estimated 157 million years of life saved, with about 20 years of additional life per each life saved (Holford, Meza et al. 2014). These analyses were prominently featured as part of activities commemorating the 50th anniversary of the first SGR on Smoking and Health. Moreover, the estimated smoking prevalence, initiation, cessation, and intensity rates in the US by birth-cohort from 1965-2009 (Holford, Levy et al. 2014) were incorporated into the SGR 50th anniversary issue: Chapter 13. Patterns of Tobacco Use Among U.S. Youth, Young Adults, and Adults.

What are the potential public health impacts of raising the minimum age for purchasing tobacco products?

CISNET investigators participated in an Institute of Medicine (IOM) Committee to assess the health consequences of raising the minimum age for purchasing tobacco products in the US. The CISNET smoking population model and the SimSmoke model were used by the IOM Committee to simulate the impact of raising the minimum age on future US smoking prevalence and several health outcomes including smoking-related mortality, lung cancer mortality, and maternal and child health outcomes. The IOM report concluded that raising the minimum age would lead to considerable positive health effects. In particular, if the minimum age were raised to age 21 nationwide, for the cohort of people born between 2000 and 2019, the models project that there would be approximately 249,000 fewer premature deaths, 45,000 fewer deaths from lung cancer, and 4.2 million fewer years of life lost. In addition, raising the minimum age would lead to improvements in maternal, fetal, and infant health outcomes by reducing the likelihood of maternal and paternal smoking. Specifically, if the minimum age were raised to 21 nationwide, the SimSmoke model projects that by 2100 there would be approximately 286,000 fewer pre-term births, 438,000 fewer cases of low birth weight, and roughly 4,000 fewer sudden infant death cases among mothers ages 15-49 (IOM report 2015).

How do smoking habits influence the initiation and promotion of lung carcinogenesis?

A two-stage clonal expansion (TSCE) model was used to analyze data from five large cohorts. The TSCE model, which is based on the biological paradigm of initiation, promotion, and progression in carcinogenesis, recognizes that carcinogenesis is a process of mutation accumulation and clonal expansion of partially altered cells on the pathway to malignancy. The model may be used to generate biological hypotheses regarding the mechanism of tobacco-induced lung cancer and to explore the extent to which projected risks depend on such biological mechanisms. The first study, using data from the British Doctors' cohort and two American Cancer Society Cohorts (Cancer Prevention Studies I and II), indicated that clonal expansion (promotion) of partially altered (initiated) cells by cigarette smoke is the dominant model mechanism (Hazelton, Clements, Moolgavkar 2005). A second study, based on analyses of data from the Nurses' Health and Health Professionals Follow-up Studies, confirmed these findings (Meza, Hazelton et al. 2008). The second study also showed that lung cancer incidence among non-smokers, continuing smokers, and ex-smokers was similar in these two cohorts, suggesting that there is little difference in lung cancer risk between men and women, whether related to smoking or not. These two studies show that the importance of smoking duration on lung cancer risk is a direct consequence of smoking-related promotion. These studies were also extended to analyze lung cancer mortality data from the Nurses' Health and Health Professionals Follow-up Studies (Hazelton, Jeon et al. 2012). These models served as central dose-response modules for several of the CISNET lung cancer models (Moolgavkar, Holford et al. 2012, Meza, ten Haaf et al. 2014).

What are the potential benefits associated with the use of low-nitrosamine smokeless tobacco products?

CISNET investigators from the Georgetown University convened expert panels to predict the mortality risks (Levy, Mumford et al. 2004) and impact on tobacco use (Levy, Mumford et al. 2006) in the United States of a "harm reduction" policy requiring that smokeless tobacco products meet low nitrosamine standards but could be marketed with a warning label consistent with the evidence of relative health risks. The panel concluded that low-nitrosamine smokeless tobacco products may have a substantially lower risk than smoking, and that the new policy could produce a modest acceleration in the decline in smoking prevalence over 5 years. Efforts to quantify the impact of policies of this type provide starting values for tobacco control modeling efforts, and provide a basis for furthering the public policy debate.