• 10/21/2007
  • Minneapolis, MN
  • Crystal Phend, Staff Writer, MedPage Today
  • MedPageToday.com

Even devoid of smoke, tobacco remains a carcinogen hazard, found researchers here.

Smokeless tobacco exposes users to at least as much of a potent carcinogen as smoking tobacco does, despite claims that it is a safer alternative, reported Stephen S. Hecht, Ph.D., of the University of Minnesota, and colleagues, in the August issue of Cancer Epidemiology, Biomarkers & Prevention.

Smokeless tobacco users had 73% higher levels of a biomarker for a nitrosamine carcinogen known as NNK than did smokers in pooled analysis of six studies (P<0.0001), they found.

NNK (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) is the worst of the strong carcinogens most prevalent in smokeless tobacco, they said. In animals, it has been shown to induce tumors in the lung, pancreas, nasal mucosa, and liver.

Their findings represent “an unacceptable risk” and weigh against oral snuff as a healthier substitute for smoking, they said. “Long-term use of nicotine replacement therapy may be a better option.”

Smokeless tobacco has been considered less toxic and carcinogenic than smoking because it has less of the harmful substances formed by burning the tobacco, they noted. Therefore, some tobacco control experts have suggested that smokers who cannot quit could switch to “low nitrosamine” smokeless tobacco to reduce their health risks, they said.

To see if this claim was true, the researchers used data collected at baseline from three intervention studies of smokers and three of smokeless tobacco users.

The 420 smokers (62% men) averaged 25.8 cigarettes per day. The 182 smokeless tobacco users (all men) averaged 4.2 tins per week of predominantly Kodiak (47.0%), Copenhagen (31.5%), or Skoal (12.7%) tobacco.

Gender, age, weight, and race were significantly different between the two groups (P<0.0001).

Exposure to the carcinogen NNK was estimated using the urinary biomarker total NNAL, which consists of NNK metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides.

After controlling for age and gender, smokeless tobacco users had significantly higher median total NNAL per milliliter of urine than did smokers (3.76 versus 2.18 pmol/mL for men median age 45, P<0.0001).

Smokeless tobacco users also had 32% higher total NNAL per milligram of creatinine than did smokers (2.83 versus 2.15 pmol/mg creatinine for men median age 45, P<0.001).

Estimated 24-hour excretion of total NNAL was higher among younger male smokeless tobacco users than younger male smokers (4.3 versus 3.5 nmol).

The levels of cotinine, a biomarker of nicotine exposure, were significantly higher in smokeless tobacco users than in smokers (42.1 versus 21.7 nmol/mL and 28.1 versus 22.2 nmol/mg creatinine, respectively, both P<0.001). The estimated mean daily cotinine levels in their urine were 49 Amol for smokeless tobacco users compared with 33 Amol for smokers.

Pharmacokinetics from other studies suggest that nicotine intake was likely similar between groups, Dr. Hecht and colleagues said.

“These results show that, in a treatment-seeking population, smokeless tobacco users strive to achieve similar nicotine levels as do cigarette smokers in order to satisfy their craving,” they wrote.

Because exposure to NNK was at least comparable in smokeless and smoking tobacco users, the findings “raise serious questions about the strategy of using smokeless tobacco as a substitute for cigarette smoking” with the rationale that smokeless tobacco is safer, the researchers said.

They pointed out that the lung cancer risk is doubtless higher for smokers than smokeless tobacco users, as cigarette smoke contains, in addition to NNK, multiple carcinogenic combustion products which are not present, or present in only low amounts, in smokeless tobacco. Furthermore, NNK is directly deposited in the lungs of smokers, which is likely to increase its carcinogenic effect in that organ. However, “the data presented here show that smokeless tobacco use is far from safe,” they concluded.

Notes:
1. Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.

2. The study was supported by grants from the National Institutes of Health. Two of the researchers reported grant support from the American Cancer Society and National Institute on Drug Abuse, respectively.