Smokeless tobacco mortality risks: an analysis of two contemporary nationally representative longitudinal mortality studies

There is substantial evidence that tobacco products are hazardous and their use carries the risk of serious disease [1, 2]. However, the type and magnitude of disease risk differs between different tobacco product categories and extent of use [2–5]. For example, researchers in the public health community have qualitatively placed tobacco products on “the continuum of risk,” with conventional cigarettes having the highest risk, an intermediate risk for smokeless tobacco (SLT) products and e-cigarettes, and tobacco use cessation as the lowest risk state [6]. Nutt et al. quantified this risk continuum based on a multi-criteria decision analysis approach, wherein the weighted score for cigarettes was 100 and SLT and other products were scored at less than 15 [7]. However, as described by the authors, a limitation of the study was the “lack of hard evidence for the harms of most products on most of the criteria.”

The purpose of this study is to provide a direct comparison between the health risks of US smokeless tobacco products and conventional cigarettes. Also, this study provides health risk data on tobacco product use states not frequently reported in the published literature. These include health risk estimates for dual users of SLT and cigarettes as well as risk estimates for former cigarette smokers who now use SLT products, which can be considered surrogates for consumers who switch from cigarette smoking to SLT use. These data can be useful in considering the implications of encouraging cigarette smokers who cannot or will not quit using tobacco products to switch to potentially lower risk alternatives such as SLT [8, 9]. For example, tobacco product switching may include a period of concurrent use of both products, such as cigarettes and SLT. From a harm reduction policy perspective, it is important to understand if concurrent use is associated with any additive or synergistic health consequences. Understanding the risks associated with concurrent use of SLT and cigarettes is also important because approximately 30% of SLT users smoke cigarettes, a rate that has been consistent over many years [10]. Also, any risks associated with switching from cigarettes to lower risk alternatives, such as SLT, should be compared with the risks of quitting all tobacco use when considering harm reduction policies. Finally, much of the published epidemiology of US SLT products is somewhat older, and the risks associated with use of tobacco products may change over time as tobacco product designs change [11, 12].

There is a clear need for a more recent evaluation of the health risks associated with SLT use; indeed, a recent publication by Timberlake et al. attempts to address this gap by conducting an analysis of the data from the National Longitudinal Mortality Study (NLMS), one of the same datasets used in the present study, although without the comparison to cigarette smoking we include [13]. In their study, an elevated risk of death due to coronary heart disease among SLT users compared to never-tobacco users was observed but without a significant excess risk for all-cause mortality. The current study adds to the growing body of evidence regarding current US SLT products by providing a comprehensive quantitative comparison of the mortality risks from a second publicly available dataset, the National Health Interview Survey (NHIS), in addition to the NLMS. Together, these surveys contain tobacco use and mortality data, spanning the mid-1980s to 2011, and allow for estimation of mortality risks, which are likely more reflective of the hazards encountered by SLT consumers in the US population using the most currently available products, including moist smokeless tobacco (MST). We use these data to derive mortality risk estimates for specific tobacco use profiles, including exclusive cigarette use, exclusive SLT use, dual cigarette/SLT use, or SLT use by former smokers. We provide evidence on relative mortality hazards regarding exclusive SLT use and cigarette smoking relative to never-tobacco use. Additionally, we assess the risk differential between former smokers currently using SLT relative to former smokers who do not use SLT to address the question of whether beneficial health outcomes related to smoking cessation are maintained if former smokers use SLT.

Public health agencies, including the United States Food and Drug Administration, acknowledge a continuum of risk among tobacco products, with combustible tobacco products (e.g., cigarettes) being the most harmful along this continuum and noncombustible tobacco products (e.g., SLT) being less harmful [6, 8, 37, 38]. Cigarette smoking is the leading preventable cause of death in the USA, primarily due to lung cancer, respiratory disease, and cardiovascular disease [2]. Studies with SLT users demonstrate that SLT products available in the USA may reduce the harm from cigarette smoking by providing a substantially lower risk alternative to those smokers who are unable or unwilling to cease using tobacco products [39–42]. However, others question the utility of SLT products in a harm reduction strategy, since these products are reported to be associated with cancers of the upper aerodigestive tract, particularly the oral cavity, esophagus, and pancreas, and cardiovascular diseases [43].

Much of the scientific concern regarding the health risks associated with SLT use relies on epidemiological studies performed several decades ago, and risks associated with tobacco product use may change over time [11]. Many SLT products available worldwide are associated with serious and often fatal diseases [1]. Globally, a wide variety of SLT products are used, many of which can be used on their own, mixed with other products (such as slaked lime [khaini]), or used as ingredients in other products (such as betel quid). In these situations, interpretation of results is complicated since study participants might be exposed to products with variable amounts of carcinogens. For example, the levels of the tobacco-specific nitrosamines are 100-fold higher in the SLT product, “Toombak”, which is available in Sudan, compared to US products [44].

In the USA, the dominant form of tobacco use was chewing tobacco until the 1920s after which, smoking of machine-made cigarettes became prevalent [45]. In the 1970s, a resurgence in SLT products occurred mainly in the form of chewing tobacco (predominantly loose leaf). MST products, although in existence since 1822, gained popularity and surpassed sales of chewing tobacco after 1980 [46] and today, represent approximately 85% of the SLT market in the USA. In a previous analysis, Henley et al. utilized data from participants in the Cancer Prevention Study (CPS)-I and CPS-II studies; participants in the CPS-I study were enrolled in 1959 with follow-up 12 years later in 1971 whereas participants in the CPS-II study were enrolled in 1982 with follow-up 18 years later in 2000 [3]. The goal of the current analysis was to supplement the collection of SLT epidemiological evidence with an updated analysis based on current health risk survey data collected through 2011. The NMLS and the NHIS are nationally representative surveys of the civilian non-institutionalized US population representing the years 1986 through 2009. These surveys are linked to NDI data, and provide vital longitudinal follow-up through December 31, 2011. Based on the NMLS and NHIS datasets, SLT users, in general, did not display a significantly increased risk for all-cause mortality, all-cancer mortality, or diseases of the heart compared to never-tobacco users. The all-cause mortality risks derived from our analysis of respondents in the NHIS and NLMS data sets are consistent with those found in the published scientific literature. The all-cause mortality HR (95% CI) for SLT users is estimated as 1.0 (0.8–1.3) for males and 1.3 (0.9–1.7) for females [3].

Additionally, SLT use had no discernable adverse effect on any of the nine leading causes of death and did not increase mortality risk for any of the major neoplasms often associated with SLT use. We noted clear indications of increased mortality risks in cigarette smokers due to all-causes, all-cancers, and diseases of the heart. The magnitudes of the excess mortality risks among cigarette smokers for the endpoints measured were very consistent between the two independently linked mortality datasets and generally consistent with those documented in the published literature [11, 34]. Previous research has shown that the health risks of dual users of SLT and cigarettes are similar to those of exclusive cigarette smokers [47]. Although there were limited numbers of deaths in the data sets used for the current analysis, we noted similar findings. We also noted that smoking cessation leads to a noticeable reduction in, but not necessarily elimination of, excess mortality risk. Here again, based on a limited sample size, our analysis found minimal or no adverse effect of SLT on this trend.

Some public health authorities have concluded that SLT use is causally associated with oral, esophageal, and pancreatic cancers [2]. Both the NMLS and NHIS datasets recorded an insufficient number of oral cancer mortality events to provide derivation of a mortality risk estimate for current SLT users. Notably, the leading cause of cancer-related mortality among smokers (about 12-fold increase over background in the two datasets analyzed) was virtually non-existent for SLT users in the NLMS and NHIS datasets.

Our results are generally concordant with those of Timberlake et al. who analyzed NMLS data and detected no excess risk of all-cause mortality, or mortality from all cancers, cerebrovascular disease, or cancers of the digestive organs or pancreas [13]. However, these authors did report an excess mortality risk for IHD (reported as coronary heart disease) (HR 1.24, 95% CI 1.05–1.46). We detected no excess diseases of the heart mortality risk due to SLT use in either dataset we examined (NLMS HR 0.82 (0.51–1.13 and NHIS HR 1.03 (0.83–1.29)) nor did we detect a significantly excess risk of mortality due to IHD in either NLMS or NHIS. However, our point estimate for IHD among current SLT users in the NLMS data set is 1.25, which is almost identical to the estimate of 1.24 reported by Timberlake et al. Our result was based on 14 IHD deaths among 1863 current SLT users while Timberlake’s was based on 86 deaths among 4919 current SLT users. Timberlake et al. analyzed the restricted access NLMS file, which included data from 1986 to 2011, while we analyzed the more limited public use NLMS file, which included data from 1993 to 2005. The difference in survey years included in the data analyzed by Timberlake et al. compared to the current study accounts for the difference in sample size and the larger confidence interval surrounding our estimate.

Our analysis is not without limitations similar to many long-term epidemiological studies. Possible misclassification of tobacco use practices, inconsistencies in tobacco use category assignments, and self-reporting of tobacco use are common problems in epidemiology studies of tobacco use. Further, reliance on baseline assessment to assign respondent tobacco use status can result in misclassification and does not fully capture all changes in tobacco use. Additionally, the follow-up period may not be long enough to completely cover the “latency period” for development of tobacco-related cancers, e.g., a 20-year latency period is often reported for lung cancer [48]. Nonetheless, our analyses identified excess health risks associated with cigarette smoking which were in close approximation with many other published studies [34]. We believe the close agreement of our results for current and former cigarette smokers with the recently published data, the concordance of two independent datasets, and the large number of observations in each data set all lend credibility to the results we observed for other tobacco use behaviors, including exclusive SLT use and dual use.

The significant health risks of cigarette smoking are well established, with over 400,000 attributable deaths estimated to occur in the USA each year [34]. Some in the public health arena have proposed a broader consideration of SLT products as a safer alternative to cigarette smoking [49]. In its 2007 report, the Royal College of Physicians Tobacco Advisory Group called for an evidence-based regulatory approach to SLT and harm reduction [38]. The evidence from our analyses supports this approach. Switching to lower risk products could provide a benefit to those adult smokers who are unable or unwilling to quit cigarettes. However, harm reduction can only be achieved if adult cigarette smokers who wish to continue using tobacco completely switch to SLT. For some, this conversion is inhibited by the belief that SLT use is as harmful as cigarette smoking; only 9% of adults in the USA consider some SLT to be safer than smoking [50, 51].

Emerging epidemiological data are helpful in evaluating the health risks of current SLT product use compared to cigarette smoking. Our analysis of two current US datasets measuring the effects of contemporary tobacco products demonstrates a clear mortality risk differential between use of current SLT products and cigarette smoking. Cigarette smokers in the surveys had an increased overall mortality risk and an increased risk for several specific causes of death (e.g., lung cancer), while SLT users consistently had comparatively lower mortality risks.