Public Release: 

Exposure to carcinogens not proportionally decreased by reduction in smoking

Journal of the National Cancer Institute

Smokers who substantially reduce the number of cigarettes they smoke per day are exposed to lower amounts of a potent tobacco carcinogen; however, the reduction in the amount or concentration of the carcinogen exposure is often transient and is not proportional to the reduction in cigarettes smoked. These study results appear in the January 21 issue of the Journal of the National Cancer Institute.

Cigarette smoking is the cause of 90% of the world's lung cancer cases, but it is not known whether smokers who reduce the number of cigarettes smoked per day also decrease their risk of lung cancer.

Stephen S. Hecht, Ph.D., of the University of Minnesota Cancer Center, Minneapolis, and colleagues set out to answer this question by measuring the metabolites of a specific tobacco carcinogen in the urine of smokers who were part of a structured smoking reduction program. The carcinogen, NNK, along with polycyclic aromatic hydrocarbons, are some of the most important tobacco carcinogens with respect to lung cancer.

The people in the study, who overall had smoked an average of 23.7 cigarettes per day, gave two urine samples 1 week apart before reducing their cigarette consumption by 25% for 2 weeks, 50% for another 2 weeks, and then by 75% for the duration of the study. Urine samples were collected at several specific points throughout the 6-month study period to measure levels of the NNK metabolites, called NNAL and NNAL-Gluc. The researchers also measured the level of the compound anatabine to biochemically verify the patients' self reports of cigarette consumption. Patients were offered nicotine replacement therapy to assist their smoking reduction efforts.

Overall, there was a reduction in NNAL and NNAL-Gluc levels at nearly all of the intervals as the 92 patients who completed the study reduced the number of cigarettes smoked each day. However, the magnitude of the reduction was generally less than the reduction in cigarettes smoked per day. For example, smokers who reduced their cigarettes per day by 55% to 90% during weeks 4 through 12 had reductions of only 27% to 51% in total NNAL. Even when smokers reduced their cigarettes per day from a mean of 24.7 at the beginning of the study to 2.60 at week 12 (a reduction of 90%), the average level of total NNAL was only reduced by 46%.

The authors suggest that the most likely explanation for the results is that people who are trying to cut back by smoking fewer cigarettes per day alter their smoking behavior by inhaling longer and deeper, which is known to alter a smoker's exposure to carcinogens. "The results indicate that some smokers may benefit from reduced smoking, but for most the effects are modest, probably due to compensation," the authors conclude.

In a commentary in the same issue of the Journal, Paolo Vineis, M.D., and his colleagues--a team of epidemiologists who participated in a 2002 working group that prepared a monograph on tobacco smoking and secondhand smoking for the International Agency for Research on Cancer (IARC)--review the evidence for a causal relationship between tobacco use and cancers not previously believed to be associated with smoking, such as cancers of the upper aero-digestive tract, stomach, liver, kidney, uterine cervix, and large bowel, and myeloid leukemia. They also summarize the causal association between cancer and tobacco use other than smoking, such as bidi, cigar, and pipe smoking.

"Although 1 billion people worldwide already smoke and more will start, individuals who stop smoking reduce their smoking-related cancer risks effectively," they write. "A balanced public health strategy is therefore needed that not only prevents young individuals from starting to smoke, but also helps adults stop smoking."

In an accompanying editorial, Scott J. Leischow, Ph.D., and Mirjana Djordjevic, Ph.D., of the Tobacco Control Research Branch at the National Cancer Institute, discuss how these two distinct but complementary papers highlight that tobacco's role as a cancer initiator and promoter not only is multifactorial and complex, but also remains one of the greatest global public health challenges. "Given the dearth of evidence supporting the viability and benefits of reduced smoking as a harm reduction strategy, and given the strong evidence that smoking cessation can have a dramatic impact on future tobacco-related morbidity and mortality, the IARC working group correctly concludes that the most dramatic health benefits in the next half century will occur if we can significantly increase the number of smokers who quit," they write.



  • Hecht et al.: Brenda Hudson, University of Minnesota, 612-624-5680,
  • Commentary: Nicolas Gaudin, International Agency for Research on Cancer, 33-4-72-73-85-67,
  • Editorial: National Cancer Institute, 301-496-6641,


  • Hecht SS, Murphy SE, Carmella SG, Zimmerman CL, Losey L, Kramarczuk I, et al. Effects of reduced cigarette smoking on the uptake of a tobacco-specific lung carcinogen. J Natl Cancer Inst 2004;96:107-15.
  • Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004;96:99-106.
  • Leischow SJ, Djordjevic. Smoking reduction and tobacco-related cancers: The more things change, the more they stay the same. J Natl Cancer Inst 2004;96:86-7.

    Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at

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