An IARC Monographs Working Group has concluded that smokeless tobacco is carcinogenic to humans, after a thorough review of the published scientific evidence. The Working Group was convened by the IARC Monographs Programme of the International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization. The Working Group also concluded that exposure to NNN and NNK, two tobacco-related nitrosamines, is carcinogenic to humans.

BACKGROUND

Smokeless tobacco is an addiction for hundreds of millions of people worldwide. Use by young people is increasing in many countries. Many types of smokeless tobacco are marketed for oral or nasal use. All contain nicotine and nitrosamines.

"The new IARC Monograph [volume 89] completes IARC's assessment of tobacco in all its forms," said Dr Peter Boyle, Director of IARC. Earlier IARC Monographs have found that tobacco smoke, passive smoking, and betel quid with tobacco are also carcinogenic to humans [volumes 83 and 85, IARC 2004]. "Tobacco is clearly the worst public health disaster of the twentieth century," added Dr Boyle.

SMOKELESS TOBACCO IS A CANCER HAZARD

Epidemiological studies from the USA, India, Pakistan, and Sweden provide sufficient evidence that smokeless tobacco causes oral cancer in humans. There is also sufficient evidence that smokeless tobacco causes pancreatic cancer in humans, a result seen in studies from the USA and Norway. The Working Group was able to rule out chance, bias, and confounding factors in reaching these conclusions. Smokeless tobacco also causes cancer at several sites in exposed rats. Details of these studies will be available next year when the Monograph is published in its full form. A summary will be published in the December issue of The Lancet Oncology ( http://oncology.thelancet.com), which is available online from November 29, 2004 and in print from December 1, 2004.

TOBACCO-RELATED NITROSAMINES

Tobacco users are exposed to differing levels of nitrosamines. These are formed mainly by nitrosation of nicotine and other tobacco alkaloids during the curing and processing of tobacco, and additional amounts are formed during smoking.

NNN and NNK are the most abundant strong carcinogens in smokeless tobacco, and their uptake and metabolic activation have been clearly established in tobacco users. Numerous studies in several animal species have established that NNN and NNK cause cancer at several sites. Epidemiological studies of tobacco users, both smoked and smokeless, support a plausible association between exposure to NNN and NNK and cancer. DNA and haemoglobin adducts are commonly detected in tobacco users, and the Working Group used this mechanistic information in its conclusion.