This eighty-ninth volume of the IARC Monographs is the third and last of a series on tobacco-related agents. Volume 83 reported on the carcinogenicity of tobacco smoke and involuntary smoking (second-hand smoke or environmental tobacco smoke) (IARC 2004a). Volume 85 summarized the evidence on the carcinogenic risk of chewing betel quid with and without tobacco (IARC 2004b). That volume explored the variety of products chewed in South Asia and other parts of the word that contain areca nut in combination with other ingredients, often including tobacco. In this eighty-ninth volume, the carcinogenic risks associated with the use of smokeless tobacco, including chewing tobacco and snuff, are considered in a first monograph. The second monograph reviews some tobacco-specific nitrosamines. These agents were evaluated earlier in Volume 37 of the Monographs (IARC 1985) and information gathered since that time has been summarized and evaluated.

This remarkable book provides updates on various aspects of tobacco - its chemical and biological nature, and its physiological effects.

A working group of sixteen experts from seven countries re-evaluated the evidence of the carcinogenicity of betel-quid and areca-nut chewing and some areca-nut related nitrosamines. Betel-quid and areca-nut chewing are widely practised in many parts of Asia and in Asian-migrant communities elsewhere in the world. There are hundreds of millions of users worldwide. They evaluated betel quid with tobacco as carcinogenic to humans (Group 1) on the basis of sufficient evidence of an increased risk of cancer of the oral cavity, pharynx and oesophagus. The working group reviewed epidemiological studies of human cancer, mainly studies from India, Pakistan and Taiwan (China). Studies on betel quid with tobacco and areca nut with tobacco in experimental animals now also provide sufficient evidence of carcinogenicity. The working group also evaluated betel quid without tobacco as carcinogenic to humans (Group 1), on the basis of sufficient evidence of an increased risk of oral cancer. Studies on betel quid without tobacco and areca nut without tobacco in experimental animals now also provide sufficient evidence of carcinogenicity. Areca nut, a common ingredient of betel quid and many different chewing preparations, including those available commercially, has been observed to cause oral submucous fibrosis

During the early 1930s, when I was a graduate student and later a post-doctoral researcher at the National Research Council for the University of Wisconsin at Madison, we had the opportunity to get acquainted with many graduate students from China who were sent to the University for training in modern basic sciences as well as social sciences. The University of Wisconsin continues to graduate a large number of Chinese students. Economic conditions in the 1930s were very precarious for the United States and other parts of the world. Many of us students grew closer together because we were living on similarly tight budgets. As a matter of fact, we subleased a part of our apartment in Madison to some Chinese graduate students. This was a very nice opportunity for us to learn about the scientific and cultural back ground of our Chinese friends. Many of them came from the interior of China and had had very little opportunity to become acquainted with people from a western culture. Living with these students was a very pleasant and educational experience which gave us a good pic ture of the cultural life and educational system of China at that time--an intimate picture that one normally would not see without travelling in that country.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.