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Erschienen in: BMC Medicine 1/2015

Open Access 01.12.2015 | Research article

Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries

verfasst von: Kamran Siddiqi, Sarwat Shah, Syed Muslim Abbas, Aishwarya Vidyasagaran, Mohammed Jawad, Omara Dogar, Aziz Sheikh

Erschienen in: BMC Medicine | Ausgabe 1/2015

Abstract

Background

Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults.

Methods

The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population’s exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies.

Results

We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia.

Conclusions

Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control.
Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12916-015-0424-2) contains supplementary material, which is available to authorized users.

Competing interests

KS, SS, SA, AV, MJ, and OD declare that they have no competing interests. AS reports grants from The Commonwealth Fund, outside the submitted work but no other conflict of interest.

Authors’ contributions

KS: Developed the protocol, data analysis, data interpretation, drafting and approval of the manuscript. SS: Data collection, data analysis, data interpretation, contribution to and approval of the manuscript. SA: Co-drafted the protocol, data collection, data analysis, contribution to and approval of the manuscript. AV: Data collection, data analysis, data interpretation, contribution to and approval of the manuscript. MJ: Data collection, data interpretation, contribution to and approval of the manuscript. OD: Contribution to the protocol, data interpretation, contribution to and approval of the manuscript. AS: Conceived the idea, contribution to the protocol, data interpretation, contribution to and approval of the manuscript.
Abkürzungen
CI
Confidence intervals
DALYs
Disability-adjusted life years
DHS
Demographic and Health Surveys
GATS
Global Adult Tobacco Survey
ICS
Individual Country Survey
PAF
Population attributable fraction
SEBS
Special Europe Barometer Survey
SLT
Smokeless tobacco
STEPS
STEPwise Approach to Surveillance
TSNA
Tobacco-specific nitrosamines
WHO
World Health Organization

Background

Smokeless tobacco (SLT) consists of a number of products containing tobacco, which are consumed—without burning—through the mouth or nose [1]. A diverse range of SLT products are available worldwide, varying in their composition, methods of preparation and consumption, and associated health risks (Table 1) [1]. Its use is most prevalent in South and South-East Asia where one-third of tobacco is consumed in smokeless form [2, 3]. Wrapped in a betel leaf with areca nut, slaked lime, and catechu, SLT is often served at social occasions in this region. Other products (e.g. gutkha, khaini) contain slaked lime, areca nut, flavourings, and aromatic substances [4]. A number of products based on powdered tobacco (e.g. snus) are also consumed in Nordic countries and North America. In other parts of world, the most commonly used SLT products (Table 1) include Chimó (Venezuela), Nass (Uzbekistan, Kyrgyzstan), Tambook (Sudan, Chad), and Snuff (Nigeria, Ghana, South Africa).
Table 1
Smokeless tobacco products consumed most commonly across the world
Smokeless tobacco products
Regions (WHO)
Countries (highest consumption)
Other ingredients
Preparation and use
pHa
Nicotinea (mg/g)
Total TSNAa (ng/g)
Snus (Swedish)
Europe (Region A)
Nordic countries (Denmark, Finland, Iceland, Norway, Sweden)
Water, sodium carbonate, sodium chloride, moisturisers, flavouring
A heat treatment process; placed between the gum and upper lip
6.6–7.2
7.8–15.2
601–723
Plug, Snuff (US), Snus (US)
Americas (Region A and B)
US, Canada, Mexico
Sweeteners, liquorice
Plug; air cured
4.7–7.8
3.9–40.1
313–76,500
Dry or moist snuff; finely ground and fire cured
Snus; steam cured
Snuff; kept between lip and gum, dry snuff can be inhaled too
Chimó
Americas (Region B)
Venezuela, Colombia
Sodium bicarbonate, brown sugar, Mamo’n tree ashes
Tobacco paste made from tobacco leaves; placed between the lip or cheek and gum and left there for some time
6.9–9.4
5.3–30.1
9390
Nass (Naswar)
Europe (Region B) and Eastern Mediterranean (Region D)
Uzbekistan, Kyrgyzstan, Tajikistan, Afghanistan, Pakistan, Iran
Lime, ash, flavourings (cardamom), indigo
Sundried and powdered; placed between lip or cheek and gum
8.4–9.1
8.9–14.2
478–1380
Tambook
Eastern Mediterranean (Region D) and Africa (Region D)
Sudan, Chad
Mixed with moist sodium bicarbonate
Fermented and grounded; placed and kept in mouth
7.3–10.1
9.6–28.2
302,000–992,000
Snuff (North and West African)
Africa (Region D)
Nigeria, Ghana, Algeria, Cameroon, Chad, Senegal
Dried tobacco leaves mixed with potassium nitrate and other salts
Dry snuff; finely ground and inhaled as a pinch
9.0–9.4
2.5–7.4
1520–2420
Moist snuff is placed in mouth
Snuff (South African)
Africa (Region E)
South Africa
Dried tobacco leaves mixed with ash
Dry snuff; finely ground and inhaled as a pinch
6.5–10.1
1.2–17.2
1710–20,500
Khaini
South East Asia (Regions B and D) Western Pacific (Region B) Eastern Mediterranean (Region D) Europe (Region A)
India, Bangladesh, Nepal, Bhutan
Slaked lime, menthol, flavourings, areca nut
Shredded; kept in mouth between lips and gum
9.6–9.8
2.5–4.8
21,600–23,900
Zarda
Bangladesh, India, Pakistan, Myanmar, Thailand, Indonesia, Nepal, Maldives, Sri Lanka, UK
Served wrapped in a betel leaf with lime, catechu, areca nuts
Shredded tobacco leaves are boiled with lime and saffron; the mixture is dried then chewed and spat
5.2–6.5
9.5–30.4
5490–53,700
Gutkha
India, Pakistan, Bangladesh, Nepal, Myanmar, Sri Lanka, UK
Betel nut, catechu, flavourings, sweeteners
Commercially manufactured; sucked, chewed, and spat
7.4–8.9
0.2–4.2
83–23,900
WHO World Health Organization, TSNA tobacco-specific nitrosamines
aFigures are adapted from Stanfill et al. [6], Lawler et al. [17], and NIH & CDC 2014 report on smokeless tobacco products [37]
In addition to nicotine, SLT products contain over 30 carcinogens [5] including tobacco-specific nitrosamines (TSNA), arsenic, beryllium, cadmium, nickel, chromium, nitrite, and nitrate. The level of nicotine and carcinogens vary between products (Table 1) [6]. For example, nicotine content among SLT products varies between 0.2 and 40.1 mg/g, compared to commercial filtered cigarettes which contain 16.3 mg/g of nicotine [7]. Their pH also varies, which, being a key determinant of the level of absorption of nicotine and carcinogens, determines its toxicity: the higher the pH, the higher the absorption and, consequently, the higher the toxicity [6]. Such considerations mean that there are substantial variations between different SLT products in the level of risk posed to human health [4, 811]. It is therefore important not to consider SLT as a single product, but rather as groups of products with differences in their toxicity and addictiveness depending upon their carcinogen, nicotine, and pH levels. The diversity in SLT toxicity has been an impediment not only in establishing its global risks to human health, but also in agreeing on international policies for its prevention and control. It is therefore perhaps unsurprising that despite several country-specific studies [1215] no attempt has hitherto been made to estimate its global disease burden.
To overcome these challenges, we developed a novel approach to estimate the global burden associated with the use of SLT products. The determinants of their toxicity (carcinogens and pH) and addictiveness (nicotine) are dependent on preparation methods, ingredients that are added to SLT products, and consumption behaviours. Given that the SLT preparations and consumption patterns are determined by, and vary with, geography and culture [16], it is possible to group them according to their availability in different parts of the world (Table 1). These groups of SLT products, classified according to different geographical regions, will also be distinguishable from each other on the basis of their toxicity, addictiveness, and associated health risks. Hence, the risks were assumed to be highest in those regions and cultures where products are combined with other ingredients, and are prepared and consumed in a way that makes them very alkaline (i.e. a high pH), and rich in nicotine and TSNA [6, 17]. Building on this assumption, we aimed to estimate the worldwide burden of disease attributable to SLT use, measured in terms of disability adjusted life years (DALYs) lost and number of deaths in 2010.

Methods

We used the comparative risk assessment method, which evaluates changes in population health (burden of disease) that result from modifying a population’s exposure to a risk factor [18, 19]. For this, we used 2010 datasets, which provided the most recent global estimates of burden of disease [20]. The estimates were calculated for individual countries and then grouped into 14 World Health Organization (WHO) sub-regions (Additional file 1: Appendix 1) [21]. These were generated through estimating the following:
1.
The prevalence of SLT consumption
 
2.
Diseases caused by SLT use
 
3.
The relative risks of acquiring these diseases
 
4.
The population attributable fraction (PAF) for each of these diseases
 
5.
The overall burden of these diseases in terms of DALYs lost and deaths
 
6.
Proportion of this burden attributable to SLT use
 

Prevalence of smokeless tobacco use

We carried out a systematic literature search (see Additional file 1: Appendix 2 for a detailed description of the methods employed) for the point prevalence (current use) of SLT consumption among all adult (≥15 years) populations, and also for men and women separately. Only one prevalence report was included for one country. Latest national prevalence data collected as part of an international or regional survey were preferred over an older isolated national or a sub-national survey. We used data from the Global Adult Tobacco Survey (GATS), where available [22]. In its absence, other international (WHO STEPwise approach to Surveillance, The Demographic and Health Surveys), regional (Special Europe Barometer), national, and/or sub-national surveys were used to extract prevalence data.

Diseases caused by smokeless tobacco use

A scoping review was carried out to identify associated diseases. A series of focused literature reviews were subsequently carried out to find and assess the evidence of causation between each of these diseases and SLT use. Our search strategies and selection criteria are provided in Additional file 1: Appendix 3. One researcher ran the searches, which were then independently scrutinised by another independent researcher who considered the search results against the pre-specified inclusion and exclusion criteria. Similarly, one researcher extracted data, which were independently crosschecked by another researcher. In particular, we appraised the studies for case definitions for diseases and for assessment methods for measuring exposure to SLT and for investigating the effects of potential confounders. We excluded those diseases (and respective studies) where evidence was not supportive of a causal relationship. Only studies that adequately controlled for smoking and/or alcohol as potential confounders either at the design or the analysis stage were carried forward into the next stage of the analysis (discussed below). Quality was assessed using the Newcastle-Ottawa Scale for assessing the quality of non-randomised studies in meta-analyses [23].

Assessing risk and meta-analyses

Risk estimates (relative risks/odds ratios) and their confidence intervals (CI) were log transformed to produce effect sizes and standard errors, respectively [24]. We carried out random effects meta-analysis using RevMan version 5 to estimate pooled risk estimates. We first obtained country-specific risk estimates (relative risks/odds ratios) for individual diseases by pooling data from the included studies carried out in respective countries. We then extrapolated non-specific global risk estimates by pooling respective country-specific risk estimates. We were mindful that the risk of acquiring diseases varies between countries owing to differences in SLT products used. Therefore, for each disease where good country-specific risk estimates (pooled estimate from a meta-analysis of three or more studies in respective country) were available, we applied these to respective countries and also to those countries and regions where similar SLT products are used. In the absence of good country-specific risk estimates, we used either one of the following two approaches: (a) In countries and regions that use SLT products with moderate to high pH and TSNAs levels, we applied non-specific global estimates (pooled estimate from a meta-analysis of all studies); and (b) in countries and regions where there was either no information available on the SLT products or the information available indicates low levels of pH and TSNA, we did not apply any estimates. Further details on the application of these assumptions across all 14 WHO regions are provided in web Additional file 1: Appendix 4. We only used those pooled relative risks (country or non-specific) that were found to be statistically significant.
Where associations were presented for more than one SLT product in the same paper, we considered these as separate studies for the purpose of meta-analysis. Similarly, where risks were given separately for former and current SLT users, these were also treated as separate studies. We did not attempt to group risks according to gender because very few studies had such sub-group analysis.

Population attributable fraction

PAF is the proportional reduction in disease or mortality that would occur if exposure were reduced to zero [25, 26]. PAF was estimated for each disease for each country for both males and females, using the following formula:
$$ \mathrm{P}\mathrm{A}\mathrm{F}={\mathrm{P}}_{\mathrm{e}}\left({\mathrm{RR}}_{\mathrm{e}}\hbox{--} 1\right)/\left[1+{\mathrm{P}}_{\mathrm{e}}\left({\mathrm{RR}}_{\mathrm{e}}\hbox{--} 1\right)\right] $$
$$ {\mathrm{P}}_{\mathrm{e}}=\mathrm{Prevalence} $$
$$ {\mathrm{RR}}_{\mathrm{e}}=\mathrm{Relative}\ \mathrm{Risk} $$

Overall burden

The overall number of DALYs and deaths for each associated disease for both males and females for each country were extracted from the 2010 Global Burden of Disease study [27, 28].

Attributable burden

The attributable burden (AB), in deaths and DALYs, was estimated for each associated disease for each country for both males and females by multiplying PAF by the overall burden of the disease (B):
$$ \mathrm{AB}=\mathrm{P}\mathrm{A}\mathrm{F}\times \mathrm{B} $$

Results

Prevalence of smokeless tobacco use

We found adult prevalence figures for SLT consumption in 115 countries (Fig. 1). The definition for ‘adult’ ranged from 15, 16, 25, or 35 years at one end to 49, 64, 65, 70, 74, 84, 85, 89, or no age limit at the other. The PRISMA diagram describing the selection of the prevalence reports is provided in Additional file 1: Appendix 5a.
In general, SLT consumption was higher among males than females (Table 2). Mauritania had the highest prevalence of SLT consumption among females (28.3 %), followed by Bangladesh (27.9 %), Madagascar (19.6 %), India (18.4 %), and Bhutan (17.3 %). Among males, Myanmar (51.4 %), Nepal (37.9 %), India (32.9 %), Uzbekistan (31.8 %), and Bangladesh (26.4 %) had the highest consumption rates. Within Europe, SLT (snus) consumption was high in Sweden (24.0 % males, 7.0 % females) and Norway (20.0 % males, 6.0 % females).
Table 2
Prevalence of smokeless tobacco use in different countries of the world according to WHO sub-regional classification
WHO sub-regions
Country
M
F
Source
Year
Africa (Region D)
Algeria
21
0.4
STEPS [38]
2005
Benin
12.7
5.7
STEPS [38]
2008
Burkina Faso
3.86
DHS [39]
2011
Cameroon
1.94
0.94
DHS [39]
2011
Cape Verde
3.5
5.8
STEPS [38]
2007
Chad
1.9
0.4
STEPS [38]
2008
Comoros
7.72
2.99
DHS [39]
2012
Gabon
0.48
0.34
DHS [39]
2012
Gambia
0.8
1.4
STEPS [38]
2010
Ghana
1.33
0.2
DHS [39]
2008
Guinea
1.4
1.5
STEPS [38]
2009
Liberia
2.3
2.4
DHS [40]
2007
Madagascar
24.66
19.6
DHS [39]
2009
Mali
5
1.2
STEPS [38]
2007
Mauritania
5.7
28.3
STEPS [38]
2006
Niger
4.55
2.3
DHS [39]
2012
Nigeria
3.2
0.5
DHS [40]
2008
Sao Tome & Principe
3.8
1.9
STEPS [38]
2009
Senegal
6.63
0.23
DHS [39]
2011
Sierra Leone
3
12
STEPS [38]
2009
Togo
5.1
2.2
STEPS [38]
2010
Africa (Region E)
Botswana
7.2
14.5
STEPS [38]
2007
Burundi
0.03
0.31
DHS [39]
2011
Congo (Brazzaville)
8.3
1.54
DHS [39]
2012
Congo (Republic)
8.67
3.22
DHS [39]
2013
Cote d'Ivoire
0.61
1.27
DHS [39]
2012
Eritrea
5.8
0.2
STEPS [38]
2004
Ethiopia
1.94
0.2
DHS [39]
2011
Kenya
2.05
1.29
DHS [39]
2008
Lesotho
1.3
9.1
DHS [40]
2009
Malawi
1.9
5
STEPS [38]
2009
Mozambique
10.94
0.82
DHS [39]
2011
Namibia
1.8
2.3
DHS [40]
2006–07
Rwanda
5.8
2.73
DHS [39]
2011
South Africa
2.4
10.9
DHS [41]
2003
Swaziland
2.6
0.8
STEPS [38]
2007
Tanzania
2.03
0.83
DHS [39]
2010
Uganda
2.94
1.5
DHS [39]
2011
Zambia
0.3
1.2
DHS [39]
2007
Zimbabwe
1.6
0.4
DHS [41]
2011
Americas (Region A)
Canada
2
ICS [41]
2011
USA
6.5
0.4
ICS [41]
2010
Americas (Region B)
Argentina
0.1
0.2
GATS [42]
2012
Barbados
0
0.6
STEPS [38]
2007
Brazil
0.6
0.3
GATS [42]
2010
Dominican Republic
1.9
0.3
DHS [40]
2007
Grenada
2.2
0.3
STEPS [38]
2011
Mexico
0.3
0.3
GATS [42]
2009
Paraguay
3
1.6
ICS [41]
2011
St Kitts & Nevisa
0.3
0.1
STEPS [38]
2007
Trinidad & Tobago
0.5
0.3
STEPS [38]
2011
Venezuela
6.2
0.9
ICS [41]
2011
Americas (Region D)
Haiti
2.5
DHS [40]
2005–06
Eastern Mediterranean (Region B)
Libya
2.2
0.1
STEPS [38]
2009
Saudi Arabia
1.3
0.5
STEPS [38]
2004
Tunisia
8.6
2.2
ICS [41]
2005–06
Eastern Mediterranean (Region D)
Egypt
4.8
0.3
GATS [42]
2009
Iraq
1.6
0.3
STEPS [38]
2006
Pakistan
16.3
2.44
DHS [43]
2012–13
Sudan
24.1
1
STEPS [38]
2005
Yemen
15.1
6.2
ICS [41]
2003
Europe (Region A)
Austria
7.8
1.1
SEBS [44]
2012
Belgium
1.1
0.6
SEBS [44]
2012
Cyprus
2.1
0.4
SEBS [44]
2012
Czech Republic
2.5
0.4
SEBS [44]
2012
Denmark
3
1
ICS [41]
2010
Finland
5.5
0.3
ICS [41]
2011
France
1.2
0.6
SEBS [44]
2012
Germany
3.4
3.4
SEBS [44]
2012
Iceland
5.97
ICS [41]
2008
Ireland
2.2
0.9
SEBS [44]
2012
Italy
1.8
1.5
SEBS [44]
2012
Luxembourg
1.8
1
SEBS [44]
2012
Malta
5.5
1.5
SEBS [44]
2012
Netherlands
0.3
0.1
ICS [41]
2011
Norway
20
6
ICS [41]
2011
Portugal
4.4
1.1
SEBS [44]
2012
Slovenia
1.8
0.4
SEBS [44]
2012
Spain
0.4
0.2
SEBS [44]
2012
Sweden
24
7
ICS [41]
2011
Switzerland
4
1.3
ICS [41]
2011
United Kingdom
1.6
0.5
SEBS [44]
2012
Europe (Region B)
Ajerbaijan
0.3
0
DHS [40]
2006
Armenia
1.8
0
DHS [40]
2005
Bulgaria
0.3
0
SEBS [44]
2012
Georgia
1
0.2
ICS [41]
2010
Kyrgyzstan
7
0.3
ICS [41]
2006
Poland
1
0.1
GATS [42]
2009
Romania
0.4
0.2
GATS [42]
2011
Slovakia
3.9
0.7
SEBS [44]
2012
Uzbekistan
31.8
0.2
DHS [40]
2002
Europe (Region C)
Latvia
5.8
0.9
ICS [41]
2010
Lithuania
1.2
0.2
SEBS [44]
2012
Moldova
0.1
0
DHS [40]
2005
Russia
1
0.2
GATS [42]
2009
Ukraine
0.5
0
GATS [42]
2010
South East Asia (Region B)
Indonesia
1.5
2
GATS [42]
2011
Sri Lanka
24.9
6.9
STEPS [38]
2006
Thailand
1.1
5.2
GATS [42]
2011
South East Asia (Region D)
Bangladesh
26.4
27.9
GATS [42]
2009
Bhutan
21.1
17.3
STEPS [38]
2007
India
32.9
18.4
GATS [42]
2009
Maldives
5.6
2.6
STEPS [38]
2011
Myanmar
51.4
16.1
STEPS [38]
2009
Nepal
37.9
6
DHS [41]
2011
Timor Leste
2.48
1.93
DHS [43]
2009–10
Western Pacific (Region A)
Australia
0.75
0.41
ICS [45]
2004
Western Pacific (Region B)
Cambodia
2.2
14.8
STEPS [38]
2010
China
0.7
0
GATS [42]
2010
Lao People’s Democratic Republic
14.6
1.1
STEPS [38]
2008
Malaysia
0.9
0.6
GATS [42]
2011
Micronesia
22.4
3
STEPS [38]
2002
Mongolia
2.8
0.5
STEPS [38]
2009
Philippines
2.8
1.2
GATS [42]
2009
Vietnam
0.3
2.3
GATS [42]
2010
DHS The Demographic and Health Surveys, ICS Individual Country Survey, GATS Global Adult Tobacco Survey, SEBS The Special Europe Barometer Survey, STEPS STEPwise approach to Surveillance
aPopulations of St Kitts and Nevis are tiny and unlikely to affect our estimates

Diseases caused by smokeless tobacco use

The initial scoping review identified a number of associated diseases, including a range of cancers, cardiovascular diseases (ischaemic heart disease and stroke), periodontal conditions, and adverse pregnancy outcomes. The subsequent more focused systematic reviews identified 53 studies (Table 3) reporting association between SLT consumption and cancers of mouth, pharynx, larynx, oesophagus, lung, and pancreas (39 studies); and cardiovascular diseases, such as ischaemic heart disease and stroke (14 studies). PRISMA flow diagrams describing the selection process of the studies identified in the literature searches are provided in Additional file 1: Appendix 5b,c. The pooled non-specific relative risks were statistically significant for cancers of the mouth, pharynx, and oesophagus (Figs. 2, 3, 4, and 5). Only statistically significant relative risks (country-specific or non-specific) were included in the model to estimate attributable risks. For example, the pooled non-specific relative risk for laryngeal cancer was 1.42 (95 % CI 0.77–2.59), and hence excluded (Additional file 1: Appendix 6). Likewise, none of the country-specific estimates for the USA were statistically significant (Additional file 1: Appendix 4). Based on the above reviews, we assumed that a causal association exists between some SLT products and cancers of the mouth, pharynx, and oesophagus, and ischaemic heart disease.
Table 3
Smokeless tobacco use and risk of cancers, ischaemic heart disease, and stroke—studies included in meta-analysis
Country
Study period
Study design
Exposure status
Inclusion of cigarette/alcohol users
Outcome
Odds ratios/relative risks (95 % confidence intervals)
Comments
Quality assessment (NOS)a
Reference
CANCERS
India
2001–2004
Case–control
Smokeless tobacco with or without additives
No/No
Oral cancer
0.49 (0.32–0.75)
Exclusive SLT users
Selection****
Anantharaman et al. 2007 [46]
Comparability**
Exposure/Outcome*
India
1996–1999
Case–control
Ever SLT users
Yes/Yes
Oral cancer
7.31 (3.79–14.1)
Never drinkers adjusted for smoking
Selection****
Balaram et al. 2002 [47]
9.19 (4.38–19.28)
Never smokers adjusted for alcohol
Comparability**
Exposure/Outcome *
India
1982–1992
Case–control
Tobacco quid chewing
Yes/No
Oral cancer
5.8 (3.6–9.34)
Adjusted for smoking
Selection***
Dikshit & Kanhere 2000 [48]
Pharyngeal cancer
1.2 (0.8–1.8)
Comparability*
Lung cancer
0.7 (0.4–1.22)
Exposure/Outcome*
India
Unclear
Case–control
Chewing tobacco
No/No
Oral cancer
10.75 (6.58–17.56)
Exclusive SLT users
Selection**
Goud et al. 1990 [49]
Comparability*
Exposure/Outcome0
India
1990–1997
Cohort
Current SLT users
No/No
Oral cancer
5.5 (3.3–9.17)
Exclusive SLT users
Selection****
Jayalekshmi et al. 2009 [50]
Former SLT users
9.2 (4.6–18.40)
Comparability*
Exposure/Outcome**
India
1990–1997
Cohort
Current SLT user
Yes/Yes
Oral cancer
2.4 (1.7–3.39)
Adjusted for smoking and alcohol
Selection****
Jayalekshmi et al. 2010 [51]
Former SLT users
2.1 (1.3–3.39)
Comparability*
Exposure/Outcome***
India
May 2005
Case–control
Ever SLT users
No/No
Oral cancer
4.23 (3.11–5.75)
Exclusive SLT users
Selection***
Jayant et al. 1977 [52]
Pharyngeal cancer
2.42 (1.74–3.37)
Comparability**
Laryngeal cancer
2.8 (2.07–3.79)
Exposure/Outcome0
Oesophageal cancer
1.55 (1.15–2.07)
India
1968
Case–control
Tobacco
Yes/No
Oral cancer
4.63 (3.50–6.14)
Exclusive chewers and non-chewers data available
Selection***
Jussawalla & Deshpande 1971 [53]
Pharyngeal cancer
3.09 (2.31–4.13)
Comparability**
Laryngeal cancer
2.29 (1.72–3.05)
Exposure/Outcome0
Oesophageal cancer
3.82 (2.84–5.13)
India
2005–2006
Case–control
Tobacco flakes
Yes/Yes
Oral cancer
7.6 (4.9–11.79)
Adjusted for smoking and alcohol
Selection****
Madani et al. 2010 [54]
Gutkha
12.7 (7–23.04)
Comparability**
Mishiri
3.0 (1.9–4.74)
Exposure/Outcome*
India
Unclear
Case–control
Chewing tobacco
Yes/Yes
Oral cancer
5.0 (3.6–6.94)
Adjusted for smoking and alcohol
Selection****
Muwonge et al. 2008 [55]
Comparability*
Exposure/Outcome*
India
1982–1984
Case–control
Chewing tobacco
Yes/No
Oral cancer
10.2 (2.6–40.02)
Adjusted for smoking
Selection***
Nandakumar et al. 1990 [56]
Comparability**
Exposure/Outcome*
India
1980–1984
Case–control
SLT users
No/No
Oral cancer
1.99 (1.41–2.81)
Exclusive SLT users
Selection**
Rao et al. 1994 [57]
Comparability0
Exposure/Outcome*
India
1952–1954
Case–control
Chewing tobacco
No/No
Oral cancer
4.85 (2.32–10.14)
Exclusive SLT users
Selection***
Sanghvi et al. 1955 [58]
Pharyngeal cancer
2.02 (0.94–4.33)
Comparability**
Laryngeal cancer
0.76 (0.37–1.56)
Exposure/Outcome0
India
1983–1984
Case–control
Snuff (males only)
Yes/Yes
Oral cancer
2.93 (0.98–8.76)
Adjusted for smoking and alcohol; adjusted effect size is only among males
Selection***
Sankaranarayan et al. 1990 [59]
Comparability0
Exposure/Outcome*
India
Not given
Case–control
Tobacco chewing
Yes/Yes
Oropharyngeal cancer
7.98 (4.11–13.58)b
Adjusted for smoking and alcohol
Selection***
Wasnik et al. 1998 [60]
Comparability**
Exposure/Outcome0
India
1991–2003
Case–control
Chewing tobacco
No/No
Oral cancer
5.88 (3.66–7.93)
Exclusive SLT users
Selection****
Subapriya e al. 2007 [61]
Comparability**
Exposure/Outcome**
India
1950–1962
Case–control
Tobacco with or without paan or lime
Yes/No
Oral and oropharyngeal cancer
41.90 (34.20–51.33)
Exclusive chewer data available
Selection**
Wahi et al. 1965 [62]
Note: data of habit was not available for the whole cohort
Comparability**
Exposure/Outcome0
Pakistan
1996–1998
Case–control
Naswar
Yes/Yes
Oral cancer
9.53 (1.73–52.50)
Adjusted for smoking and alcohol
Selection***
Merchant et al. 2000 [63]
Paan with tobacco
8.42 (2.31–30.69)
Comparability**
Exposure/Outcome*
Sweden
1973–2002
Cohort
Snus
Yes/Yes
Oral and pharyngeal combined
3.10 (1.50–6.41)
Adjusted for smoking and alcohol
Selection**
Roosar et al. 2008 [64]
Comparability**
Outcome***
India
1993–1999
Case–control
Chewing tobacco
Yes/Yes
Oral cancer
5.05 (4.26–5.99)
Adjusted for smoking and alcohol
Selection***
Znaor et al. 2003 [65]
Pharynx
1.83 (1.43–2.34)
Comparability**
Oesophagus
2.06 (1.62–2.62)
Exposure/Outcome*
Norway
1966–2001
Cohort
Chewing tobacco plus oral snuff
No/No
Oral cancer
1.1 (0.5–2.42)
Adjusted for smoking, might be confounded by alcohol use
Selection***
Bofetta et al. 2005 [66]
Oesophageal cancer
1.4 (0.61–3.21)
Comparability*
Pancreatic cancer
1.67 (1.12–2.49)
Exposure/Outcome***
Lung cancer
0.80 (0.61–1.05)
Sweden
1988–1991
Case–control
Oral snuff
Yes/Yes
Oral cancer
1.4 (0.8–2.45)
Adjusted for smoking and alcohol
Selection**
Lewin et al. 1998 [67]
Larynx
0.9 (0.5–1.62)
Comparability**
Oesophagus
1.2 (0.7–2.06)
Exposure/Outcome*
Pharynx
0.7 (0.4–1.22)
Sweden
1969–1992
Cohort
Snus
No/No
Oral cancer
0.8 (0.4–1.60)
Exclusive SLT users
Selection***
Luo et al. 2007 [68]
Lung cancer
0.8 (0.5–1.28)
Comparability*
Pancreatic cancer
2 (1.20–3.33)
Exposure/Outcome***
Sweden
2000–2004
Case–control
Oral snuff
Yes/Yes
Oral
0.70 (0.3–1.63)
Adjusted for smoking and alcohol
Selection***
Rosenquist et al 2005 [69]
Comparability**
Exposure/Outcome**
Sweden
1980–1989
Case–control
Oral snuff
Yes/Yes
Oral cancer
0.8 (0.5–1.28)
Adjusted for smoking and alcohol
Selection**
Schildt et al. 1998 [70]
Comparability**
Exposure/Outcome***
USA
1972–1983
Case–control
Oral snuff
Yes/Yes
Oral cancer
0.8 (0.4–1.60)
Not clear if adjusted for smoking and alcohol
Selection**
Mashberg et al. 1993 [71]
Chewing tobacco
1 (0.7–1.43)
Comparability0
Exposure/Outcome*
USA
Not given
Case–control
SLT use
Yes/Yes
Oral cancer
0.90 (0.38–2.13)
Adjusted for smoking and alcohol
Selection***
Zhou et al. 2013 [15]
Pharyngeal cancer
1.59 (0.84–3.01)
Comparability**
Laryngeal cancer
0.67 (0.19–2.36)
Exposure/Outcome*
India
2001–2004
Case–control
Chewing tobacco
No/No
Pharyngeal cancer
3.18 (1.92–5.27)
Exclusive SLT users
Selection***
Sapkota et al. 2007 [72]
Laryngeal cancer
0.95 (0.52–1.74)
Comparability**
Exposure/Outcome*
Pakistan
1998–2002
Case–control
Snuff dipping
No/No
Oesophageal cancer
4.1 (1.3–12.93)
Adjusted for areca nut
Selection***
Akhtar et al. 2012 [73]
Quid with tobacco
14.2 (6.4–31.50)
Comparability**
Exposure/Outcome**
India
2008–2012
Case–control
Nass chewing
No/No
Oesophageal cancer
2.88 (2.06–4.03)
Exclusive SLT users
Selection***
Dar et al. 2012 [74]
Gutkha chewing
2.87 (0.87–9.47)
Comparability**
Exposure/Outcome**
India
2007–2011
Case–control
Oral snuff
Yes/Yes
Oesophageal cancer
3.86 (2.46–6.06)
Adjusted for smoking and alcohol
Selection**
Sehgal et al. 2012 [75]
Comparability**
Exposure/Outcome*
India
2011–2012
Case–control
Chewing tobacco
Yes/Yes
Oesophageal cancer
2.63 (1.53–4.52)
Adjusted for smoking and alcohol
Selection***
Talukdar et al. 2013 [76]
Comparability**
Exposure/Outcome*
Sweden
1995–1997
Case–control
Oral snuff
Yes/Yes
Oesophageal cancer (adenocarcinoma)
1.2 (0.7–2.06)
Adjusted for smoking and alcohol
Selection***
Lagergren et al. 2000 [77]
(Squamous cell carcinoma)
1.4 (0.9–2.18)
Comparability**
Exposure/Outcome*
Sweden
1969–1993
Cohort
Oral snuff
Yes/No
Oesophageal cancer (Adenocarcinoma)
1.3 (0.8–2.11)
Adjusted for smoking
Selection**
Zendehdel et al. 2008 [78]
(Squamous cell carcinoma)
1.2 (0.8–1.80)
Comparability*
Exposure/Outcome**
Sweden
1974–1985
Cohort
SLT users
No/NA
Lung cancer
0.90 (0.20– 4.05)
Adjusted for age, region of origin
Selection***
Bolinder et al. 1994 [79]
Comparability*
Outcome**
Morocco
1996–1998
Case–control
SLT users
Yes/No
Lung cancer
1.05 (0.28–3.94)
Adjusted for smoking
Selection**
Sasco et al. 2002 [80]
Comparability**
Exposure/Outcome**
USA
1977–1984
Case–control
SLT users
Yes/No
Oesophageal cancer
1.2 (0.1–14.40)
Adjusted for smoking
Selection***
Brown et al. 1988 [81]
Comparability**
Exposure/Outcome**
USA
1986–1989
Case–control
SLT users
Yes/No
Pancreatic cancer
1.4 (0.5–3.92)
Adjusted for smoking
Selection***
Alguacil & Silverman 2004 [82]
Comparability*
Exposure/Outcome**
USA
2000–2006
Case–control
Chewing tobacco
Yes/Yes
Pancreatic cancer
0.6 (0.3–1.20)
Adjusted for smoking and alcohol
Selection****
Hassan et al. 2007 [83]
Oral snuff
0.5 (0.1–2.5)
Comparability**
Exposure/Outcome*
CARDIOVASCULAR DISEASES (ischaemic heart disease and stroke)
52 countries
1999–2003
Case–control
Chewing tobacco
No/Yes
Myocardial infarction
1.57 (1.24–1.99)
Adjusted for diabetes, abdominal obesity, hypertension, exercise, diet
Selection****
Teo et al. 2006 [29]
Comparability**
Exposure/Outcome*
Pakistan
2005–2011
Case–control
Dippers only (Naswar)
No/NA
Myocardial infarction
1.46 (1.20–1.77)
Adjusted for age, sex, region, ethnicity
Selection****
Alexander 2013 [84]
Chewers only (Paan/ Supari/ Gutkha)
1.71 (1.46–2.00)
Comparability**
Exposure/Outcome**
Bangladesh
2006–2007
Case–control
Ever SLT users
No/NA
Myocardial infarction, Angina pectoris
2.8 (1.1–7.13)
Adjusted for age, sex, hypertension
Selection***
Rahman & Zaman 2008 [85]
Comparability**
Exposure/Outcome*
Bangladesh
2010
Case–control
Ever SLT users
No/NA
Myocardial infarction, Angina pectoris
0.77 (0.52–1.14)
Adjusted for age, hypertension, diabetes, acute psycho-social stress
Selection****
Rahman et al. 2012 [86]
Comparability**
Exposure/Outcome*
Sweden
1998–2005
Case–control
Current SLT users
No/NA
Myocardial infarction
0.73 (0.35–1.52)
Exclusive SLT users
Selection***
Hergens et al. 2005 [87]
Former SLT users
1.2 (0.46–3.13)
Comparability**
Exposure/Outcome**
Sweden
1978–2004
Cohort
Ever SLT users
No/NA
Myocardial infarction
0.99 (0.90–1.10)
Adjusted for age, BMI, region of residence
Selection**
Hergens et al. 2007 [88]
Comparability**
Exposure/Outcome***
Sweden
1989–1991
Case–control
Regular SLT users
Yes/NA
Myocardial infarction
1.01 (0.66–1.55)c
Adjusted for age, education, smoking
Selection***
Huhtasaari et al. 1992 [89]
Comparability**
Exposure/Outcome*
Sweden
1991–1993
Case–control
Former SLT users
No/NA
Myocardial infarction
1.23 (0.54–2.82)
Exclusive SLT users
Selection****
Huhtasaari et al. 1999 [90]
Comparability**
Exposure/Outcome**
Sweden
1988–2000
Cohort
Daily SLT users
No/NA
Ischaemic heart disease
1.41 (0.61–3.28)
Adjusted for BMI, physical activity, diabetes, hypertension
Selection****
Johansson et al. 2005 [91]
Comparability**
Exposure/Outcome**
Sweden
1985–1999
Case–control
Current SLT users
No/NA
Myocardial infarction
0.82 (0.46–1.46)
Adjusted for BMI, physical activity, education, cholesterol
Selection****
Wennberg et al. 2007 [92]
Former SLT users
0.66 (0.32–1.36)
Comparability**
Exposure/Outcome**
Sweden
1985–2000
Case–control
Regular SLT users
No/NA
Stroke
0.87 (0.41–1.83)
Adjusted for diabetes, hypertension, education, marital status, cholesterol
Selection****
Asplund et al. 2003 [93]
Comparability**
Exposure/Outcome**
Sweden
1978–2003
Cohort
Ever SLT users
No/NA
Stroke
1.02 (0.92–1.13)
Adjusted for age, BMI, region of residence
Selection**
Hergens et al. 2008 [94]
Comparability**
Exposure/Outcome***
Sweden
1998–2005
Cohort
Current SLT users
No/NA
Ischaemic heart disease
0.85 (0.51–1.42)
Adjusted for age, hypertension, diabetes, cholesterol
Selection***
Hansson et al. 2009 [95]
Former SLT users
Stroke
1.07 (0.56–2.04)
Comparability**
1.18 (0.67–2.08)
Exposure/Outcome**
1.35 (0.65–2.82)
Sweden
1991–2004
Cohort
SLT users
No/NA
Myocardial infarction
0.75 (0.3–1.87)
Adjusted for age, diabetes, occupation, hypertension, physical activity, BMI, marital status
Selection***
Janzon et al. 2009 [96]
Stroke
0.59 (0.2–1.5)
Comparability**
Exposure/Outcome**
BMI body mass index, NA not applicable, NOS Newcastle-Ottawa Scale, SLT smokeless tobacco
aNOS for assessing the quality of non-randomised studies in meta-analyses based on selection, comparability, and exposure/outcome. Number of stars (*) indicates the number of criteria met for each of these three categories [23]
bEffect sizes are for oral and pharyngeal cancers combined and were included in the meta-analysis for oral cancer only
cBased on parameter estimate and standard error reported in paper

Relative risks

Based on 32 studies, the estimated pooled non-specific relative risk for mouth (oral cavity, tongue, and lip) cancers was 3.43 (95 % CI 2.26–5.19) (Fig. 2). Studies from South-East Asia indicated an increased risk of oral cancer for SLT use whereas results from studies pertaining to Europe and the Americas did not substantiate such an association. For cancers of the pharynx, pooled non-specific relative risk was 2.23 (95 % CI 1.55–3.20), based on ten studies (Fig. 3). For oesophageal cancers, no clear increased risk was present in studies in the USA, whereas a pooled estimate reported a relative risk of 2.17 (95 % CI 1.70–2.78) (Fig. 4). For ischaemic heart disease, no good country-specific risk estimates were available (Fig. 5). However, we found one large case–control study (INTERHEART study) [29] conducted in 52 countries from all regions showing a statistically significant risk of ischaemic heart disease (adjusted odds ratio 1.57, 95 % CI 1.24–1.99) among SLT users.

Applying risk estimates

For cancers in general, pooled country-specific risk estimates obtained from Sweden and the USA were applied to Europe A and Americas A, respectively. For South-East Asia B and D and Western Pacific B regions, country-specific estimates from India were applied. There were a few exceptions to this rule, because some countries (UK, Mexico, Pakistan, China, Mongolia) differed in their SLT consumption patterns from their respective regions (see Additional file 1: Appendix 4 for details). In short, country-specific risk estimates for cancers could only be fully applied to five regions. For the remaining nine regions, our findings were imputed either by applying statistically significant non-specific risk estimates or none at all (Additional file 1: Appendix 4). In case of ischaemic heart disease, Sweden was the only country with a pooled country-specific relative risk (0.98, 95 % CI 0.90–1.07) obtained from a good number (more than three) of studies. For 11 out of 14 regions, we used a large multi-country study (INTERHEART)—conducted in 52 countries—to apply and deduce risk estimates. The three regions (Europe A and C and Americas D) were excluded, as these were not among those regions included in the INTERHEART study (Additional file 1: Appendix 4). There was one exception (UK) where INTERHEART study estimates were applied because SLT products consumed in the UK commonly originate from South Asia.

Attributable burden

The attributable burden of SLT use is outlined in Table 4. Our estimates indicate that in 2010, SLT use led to 1,711,539 DALYs lost and 62,283 deaths due to cancers of mouth, pharynx, and oesophagus, and, based on data from the benchmark 52 country INTERHEART study, 4,725,381 DALYs lost and 204,309 deaths from ischaemic heart disease. In total, SLT use caused the loss of 6,436,920 DALYs and 266,592 deaths. The figures show that three-quarters of these deaths and loss of DALYs were among males. This disease burden was found to be distributed across all WHO sub-regions. However, nearly 85 % of the total burden attributable to SLT use was in South-East Asia, with India alone accounting for 74 % of the global burden, followed by Bangladesh (5 %).
Table 4
Number of DALYs lost and deaths from SLT use in 2010, by WHO sub-region as defined in Additional file 1: Appendix 1
WHO sub-regionsa
Mouth cancer
Pharyngeal cancer
Oesophageal cancer
Ischaemic heart disease
All causes
 
M
F
All
M
F
All
M
F
All
M
F
All
M
F
All
DEATHS
Africa D
86
36
123
15
2
17
157
77
233
2323
751
3074
2581
866
3448
Africa E
155
85
240
19
12
31
389
252
641
1202
923
2125
1765
1272
3037
Americas A
0
0
0
0
0
0
0
0
0
10,240
649
10,889
10,240
649
10,889
Americas B
90
11
102
28
3
31
74
9
83
1030
291
1321
1222
314
1536
Americas D
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Eastern Mediterranean B
11
1
12
1
0
2
4
1
5
441
74
515
457
76
534
Eastern Mediterranean D
933
254
1187
604
59
663
1012
129
1141
7401
926
8327
9950
1368
11,318
Europe A
66
13
78
16
2
18
244
38
282
539
145
684
865
197
1062
Europe B
146
3
148
57
1
58
260
2
262
5506
156
5662
5969
162
6130
Europe C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
South-East Asia B
438
396
835
129
58
187
243
139
382
3205
1852
5057
4016
2445
6461
South-East Asia D
11,527
6459
17,987
12,715
3485
16,200
15,247
5625
20,873
117,523
45,047
162,570
157,013
60,617
217,630
Western Pacific A
0
0
0
0
0
0
0
0
0
69
36
104
69
36
104
Western Pacific B
134
159
293
22
34
56
51
63
114
3167
814
3981
3374
1070
4443
Worldwide
13,586
7418
21,003
13,608
3656
17,264
17,680
6336
24,016
152,647
51,662
204,309
197,520
69,072
266,592
DALYs
Africa D
2516
1046
3562
452
65
517
4119
1906
6024
64,043
19,116
83,159
71,130
22,132
93,262
Africa E
4926
2293
7220
573
349
922
10,159
6290
16,449
33,502
21,109
54,610
49,159
30,042
79,201
Americas A
0
0
0
0
0
0
0
0
0
172,206
7213
179,419
172,206
7213
179,419
Americas B
2311
230
2541
734
63
797
1717
176
1893
22,252
4728
26,980
27,014
5197
32,210
Americas D
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Eastern Mediterranean B
285
36
321
33
9
43
86
20
106
9841
1383
11,224
10,246
1448
11,694
Eastern Mediterranean D
29,240
7669
36,909
16,446
1800
18,247
27,777
3613
31,390
187,394
21,544
208,938
260,857
34,627
295,483
Europe A
1514
224
1738
369
45
414
4949
545
5494
8397
1491
9888
15,230
2304
17,534
Europe B
4439
60
4499
1704
20
1724
6460
56
6517
115,640
1991
117,631
128,243
2128
130,371
Europe C
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
South-East Asia B
10,968
7741
18,709
3217
1487
4704
5608
2983
8591
66,969
29,913
96,881
86,762
42,124
128,886
South-East Asia D
351,752
179,051
530,803
338,976
107,041
446,017
400,770
143,146
543,916
290,6993
938,528
3,845,521
3,998,491
1,367,766
5,366,257
Western Pacific A
0
0
0
0
0
0
0
0
0
1024
340
1364
1024
340
1364
Western Pacific B
3700
3567
7267
615
794
1409
1313
1485
2797
72,936
16,830
89,766
78,564
22,675
101,239
Worldwide
411,652
201,918
613,569
363,120
111,673
474,793
462,957
160,219
623,177
3,661,195
1,064,186
4,725,381
4,898,924
1,537,996
6,436,920

Discussion

We have found that SLT is consumed worldwide and that its use results in substantial, potentially avoidable, morbidity and mortality. However, owing to marked differences in the types of products available, patterns of consumption, and associated risks, there are substantial differences in the attributable burden between regions and countries. In particular, SLT consumption in South-East Asia leads to a much greater burden of disease than in Sweden, despite its use being equally prevalent. This is due to the much lower levels of TSNA and pH in SLT products in Sweden compared to those found in SLT in South-East Asia [6]. Similarly, SLT products used in the USA have lower risk estimates than for those used in South-East Asia.
We found that more than six million DALYs were lost and over a quarter of a million deaths occurred in 2010 owing to SLT consumption. However, our estimates require cautious interpretation because of a number of potential limitations.
First, our analysis was limited to those countries and diseases for which reliable prevalence and risk data were available, respectively. Most global tobacco surveys that reported on SLT consumption did not include all countries in the world. While global figures on smoking prevalence were available, we did not find any SLT prevalence figures for almost half of all countries. Where SLT prevalence figures were available, two countries (Micronesia and Saint Kitts & Nevis) were excluded from the final estimates owing to an absence of data for cancers in the 2010 Global Burden of Disease study. Moreover, for certain disease outcomes, e.g. adverse reproductive and oral health effects, poor quality as well as limited quantity of evidence precluded their inclusion.
Second, lack of country-specific risk estimates leads to considerable uncertainty. Despite several countries reporting SLT consumption, most did not have any reliable information on the types of SLT products used and on their associated health risks. For example, studies from several African countries reported high SLT consumption (Table 2), but provided little information on their hazard profile. There is some evidence, mainly from Sudan [30], that products used in Africa tend to have a higher pH than those used in Europe or in the USA. However, we did not find any data on the risks associated with widespread SLT use in southern parts of Africa. Likewise, various forms of SLT have been used in parts of South America (Brazilian rapê or Venezuelan chimó) for many years, yet there are no studies on the health effects of such products. In the absence of country-specific risk estimates, we assumed that in general those populations that consume similar SLT products are likely to share similar health risks and susceptibilities. We extrapolated and applied risk estimates to most countries included in our analysis on that basis (Additional file 1: Appendix 4). For cancer, our extrapolation was based on estimates obtained from several studies; for ischaemic heart diseases, extrapolations were mostly based on a single although large multi-country study (INTERHEART). As a result, almost three-quarters of the estimated SLT disease burden, which is attributed to ischaemic heart disease, is uncertain. Therefore, a cautious interpretation would be to exclude ischaemic heart disease burden figures from our estimates. However, in estimating these figures we had already excluded those regions and their respective countries that were not included in INTERHEART study. As a pointer on future research, our study highlights the need to study risk of SLT consumption on ischaemic heart diseases across the spectrum of SLT products and consumption behaviours. In time, this will produce more country-specific risk estimates, which would undoubtedly improve the reliability of our estimates presented here.
Third, the disease burden observed in 2010 is unlikely to be a consequence of SLT consumption in recent years. Therefore, our prevalence figures, obtained in surveys carried out in the last decade and used in the estimates, could be problematic. However, we assumed that the SLT consumption rates have remained stable over the last 30–40 years in these countries. We consider this as a safe assumption given that SLT use is not a new trend and historically embedded in culture and tradition in many countries, most remarkably in South Asia [31]. Consumption trends based on repeated youth surveys in India and Bangladesh suggest that SLT use has remained stable over the last decade [32]. Evidence from Sweden suggests that while more people are using snus now than 25 years ago, the consumption trends, compared to cigarette use, have essentially remained stable in this period [33, 34].
Finally, the age range of the adult sampling frames used in different SLT prevalence surveys varied, which could also increase uncertainty. The main difference between two of the key categories used was in the adult range starting from either ≥15 years or ≥25 years. Given that the risk of cancers and ischemic heart disease accumulates after many years of use well beyond young adult age, it may not have made much of a difference to our burden of disease estimates.
For the seven countries in South-East Asia region D, we estimated that 55,060 deaths caused by cancers of mouth, pharynx, and oesophagus, could be attributed to SLT in 2010. This is a little higher than the estimates from a recent study in which 50,000 deaths were attributed to SLT in eight South Asian countries [4]. This discrepancy may be explained by the fact that we used the most recent, updated prevalence and burden of disease figures.
Our estimate does not include economic impact. However, given the nature of the associated diseases, it is likely that the SLT use imposes a huge economic burden on weak health systems and poor economies. Moreover, owing to higher consumption of SLT among people of lower socio-economic status and inequitable access to health care in low-income and middle-income countries, its use is likely to contribute to driving disadvantaged sections of these societies into further poverty. A disproportionate impact on the male population (more than 70 % of disease burden due to SLT is in males) is also likely to have a disproportionate economic impact on societies in terms of reduced workforce contributions by men. On the other hand, effective legislation, policy, and preventive programmes could avert this burden due to SLT.
The signatories of the WHO’s Framework Convention on Tobacco Control should, in addition to the focus on reducing smoking consumption and related harm, now also consider the need to regulate production, marketing, and labelling of SLT products. This is particularly necessary in those countries where prevalence is high and SLT products are manufactured at a large scale without any checks on the carcinogenic level of their ingredients [35]. In countries where its use is largely limited to immigrant populations (such as in the UK) [36], strict regulation and taxation policies should be enforced which prevent import of SLT products and sale by local shops.
SLT is an important health issue, applying to a large part of the world. The data presented here are the most comprehensive gathered and brought together thus far. However, considerable uncertainties remain pertaining to risk estimation of different diseases associated with SLT use. Therefore more research is needed to investigate the newly established and previously known adverse health outcomes pertaining to SLT, particularly within countries where prevalence is high but no research evidence of risk estimation is available. Moreover, more descriptive questions about the type of SLT products and the pattern of use should be introduced into national surveys and publications of such findings encompassing all the regions.

Conclusions

Our study, a first attempt to assess global burden of disease due to SLT, estimates that more than six million DALYs are lost and over a quarter of a million deaths occur each year owing to its consumption. There is a need to build on the insights obtained from efforts to reduce cigarette smoking-related harm and to investigate strategies to reduce use of SLT and decrease the substantial associated burden of harm.

Funding

This study was funded by grants received from Leeds City Council, Leeds, UK and Medical Research Council, UK (MC_PC_13081).

Ethics approval

No ethics approval was required for this study.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

Competing interests

KS, SS, SA, AV, MJ, and OD declare that they have no competing interests. AS reports grants from The Commonwealth Fund, outside the submitted work but no other conflict of interest.

Authors’ contributions

KS: Developed the protocol, data analysis, data interpretation, drafting and approval of the manuscript. SS: Data collection, data analysis, data interpretation, contribution to and approval of the manuscript. SA: Co-drafted the protocol, data collection, data analysis, contribution to and approval of the manuscript. AV: Data collection, data analysis, data interpretation, contribution to and approval of the manuscript. MJ: Data collection, data interpretation, contribution to and approval of the manuscript. OD: Contribution to the protocol, data interpretation, contribution to and approval of the manuscript. AS: Conceived the idea, contribution to the protocol, data interpretation, contribution to and approval of the manuscript.
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Metadaten
Titel
Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries
verfasst von
Kamran Siddiqi
Sarwat Shah
Syed Muslim Abbas
Aishwarya Vidyasagaran
Mohammed Jawad
Omara Dogar
Aziz Sheikh
Publikationsdatum
01.12.2015
Verlag
BioMed Central
Erschienen in
BMC Medicine / Ausgabe 1/2015
Elektronische ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0424-2

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