B142

Gritz et al. (Cancer Epi Biom Prev 16:859, 2007) call for increased research to reduce risk of lung cancer in smokers, but do not mention question of safer cigarettes, which offer most immediate promise for reducing risk of lung cancer. Most smoking-related lung cancer is almost certainly induced by chemical carcinogens, especially tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and polycyclic aromatic hydrocarbons (PAH), both of which can induce lung cancer in animals. Cigarettes show large world-wide variations in TSNA content, with highest levels in U.S.A. Cigarette TSNA and nitrate levels were strongly correlated, suggesting that TSNA arise from reaciton of amines with nitrate-derived nitrite in tobacco. TSNA level was not correlated with tar content of mainstream cigarette smoke. Most evidence indicates that TSNA in cigarette smoke arise by transfer of TSNA (which are somewhat volatile) in cigarettes. Hence lowering TSNA levels in cigarettes should reduce smokers’ exposure to TSNA. Mean TSNA content was 2.8 μg/g Swedish snuff (“ethan snus”) compared to 33 μg/g for all U.S. snuff brands. Apparently, TSNA level in snus are low mainly because it is manufactured by heating freshly picked tobacco leaves with steam, which produces relatively sterile and dry tobacco, whereas U.S. cigarette and snuff tobacco is stored for weeks in moist curing barns. Storage causes proliferation of bacteria that reduce nitrate to nitrite, which can produce nitrosamines by bacteria-catalyzed or chemical nitrosation. Also, snus is kept refrigerated in stores selling the product. Previous efforts to reduce risk by marketing low-tar low-nicotine cigarettes failed because cigarettes were smoked more intensely or more often to maintain blood nicotine levels. Recent increased prevalence of lung adenocarcinoma compared to lung squamous cell carcinoma could be due to reduction of PAH but not TSNA levels in filter cigarettes. Therefore, to lower TSNA levels in cigarettes, we should (a) reduce application of nitrate fertilizer to tobacco plants, (b) use tobacco strains that produce low TSNA yields and, especially, (c) cure and store tobacco by methods used for snus. Such measures are unlikely to lower incidence of smoking-induced deaths from heart disease, stroke and emphysema, which cause most deaths due to smoking and are probably not due to TSNA or PAH. However, these changes may prevent a large proportion of deaths due to lung cancer (160.000/year in U.S.A.). I thank Steven S. Hecht (Univ. Minn. Cancer Center, Minneapolis, MN) for advice and help with literature.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA