We identified epidemiological studies of smokeless tobacco and cancer based on the IARC Monograph, which was prepared in October, 2004, and provides a very detailed review of the studies available at that time,4 and by searching Medline, PubMed, and references from relevant articles for reports published in any language between October, 2004, and September, 2007, using the search terms “snus”, “snuff”, or “smokeless tobacco”, and “cancer” or “neoplasm”. Meeting abstracts and reports were
ReviewSmokeless tobacco and cancer
Introduction
Use of oral and nasal smokeless tobacco products has been common in many countries for centuries (figure 1). During most of the 20th century, use of these products has been common in India and other Asian countries, as well as in parts of Africa, but has declined in northern Europe and North America. However, during the past decades, an increase in use has been seen in the USA and some northern European countries, especially by young people.
Section snippets
Products and patterns of use
Smokeless tobacco is consumed without burning the product, and can be used orally or nasally. Oral smokeless tobacco products are placed in the mouth, cheek, or lip, and are sucked (dipped) or chewed. Chewing tobacco can be classified as loose leaf (made from cigar leaf tobacco that is air-cured, sweetened, and loosely packed), plug (made from heavier grades of tobacco leaves harvested from the top of the plant, immersed in a mixture of licorice and sugar and pressed into a plug), or twist
Carcinogens in smokeless tobacco
More than 30 carcinogens exist in smokeless tobacco, including volatile and tobacco-specific nitrosamines, nitrosamino acids, polycyclic aromatic hydrocarbons, aldehydes, metals.4 Smokeless tobacco use entails the highest known non-occupational human exposure to carcinogenic nitrosamines, which is 100–1000 times greater than exposure in foods and beverages commonly containing nitrosamine carcinogens. Every gram of commonly used smokeless tobacco contains 1–5 μg of the tobacco-specific
Oral use—studies from Europe and North America
13 separate risk estimates have been made available from 11 studies examining the risk of oral cancer (oral and pharyngeal cancer in six studies) in users of smokeless tobacco products (table 1). Summary relative risk was 1·8 (95% CI 1·1–2·9), with evidence of heterogeneity in the results (table 2). When stratified by geographic region, the increased risk was restricted to the studies from the USA, whereas no increased risk was reported in the studies from Norway and Sweden (four risk
Health effects other than cancer
Many cross-sectional studies from the USA, India, Saudi Arabia, Uzbekistan, and Sudan reported a higher occurrence of oral soft tissue lesions in smokeless tobacco users than in non-users.4 Most of the studies have accounted for tobacco smoking either by statistical adjustment or restriction to non-smokers. The lesions are described as leucoplakia, erythroplakia, snuff dipper's lesion, tobacco and lime user's lesion, verrucous hyperplasia, and submucosal deposits, and tend to be seen in the
Burden of smokeless tobacco-related cancer
The fraction attributable cancers (AF) is a measure of the burden of smokeless tobacco use on human cancer. It refers to the role of past exposure on current cancer burden, and, if exposure has changed (as has occurred in the composition of smokeless tobacco products used in North America and Europe), it cannot be applied to the effect of current exposure on future cancer. Attributable cancers can be estimated based on the relative risk due to the habit (RR) and the proportion of the exposed
Biomarkers of carcinogen exposure in smokeless tobacco users
Biomarker studies clearly show the uptake and metabolism of tobacco carcinogens by smokeless tobacco users. These studies are crucial in linking smokeless tobacco use to cancer outcomes. Human beings and laboratory animals metabolise NNK into NNAL and NNK's glucuronides (NNAL-Glucs).17 These compounds are excreted in the urine, and the total amount, known as total NNAL, is a practical and widely used biomarker of NNK exposure.59
The carcinogenic properties of NNAL are quite similar to those of
Mechanisms of carcinogenicity of smokeless tobacco
Figure 3 presents a conceptual framework for the carcinogenic mechanism by smokeless tobacco. People begin using these products generally at a young age, frequently because of effective marketing and peer pressure. These individuals become addicted to nicotine and cannot stop using the products. Nicotine is not a carcinogen, but as described above, every dip of smokeless tobacco contains more than 30 established carcinogens, with especially high amounts of the tobacco-specific nitrosamines NNK
Conclusion
We do not intend to address explicitly the use of smokeless tobacco to reduce the risk from tobacco smoking—eg, by promoting smokers to switch to smokeless products or by introducing these products in a population where the habit is not prevalent. Nevertheless, several conclusions can be reached based on the available data: use of smokeless tobacco products is widespread in many populations, but their health effects (especially with respect to cancer risk) need to be better characterised; such
Search strategy and selection criteria
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