© 2004 by Oxford University Press
© 2004 Oxford University Press
IN THIS ISSUE |
Although tobacco products with reportedly reduced carcinogen content are being marketed, carcinogen uptake in people who use these products compared with that in people using medicinal nicotine has not been assessed systematically. In a randomized study, Hatsukami et al. (p. 844) compared carcinogen uptake in users of smokeless tobacco who switched to Swedish snus or cigarette smokers who switched to OMNI cigarettes with that of men who quit and used the nicotine patch. The authors found that metabolite levels of a tobacco-specific carcinogen were much lower in men who switched to snus or to the nicotine patch than they were before the switch and in men who switched to OMNI cigarettes or to the nicotine patch. Cigarette smokers who switched to the patch also had reduced levels of a biomarker of polycyclic aromatic hydrocarbon uptake. The authors conclude that switching to reduced-carcinogen tobacco products or medicinal nicotine can decrease levels of tobacco-associated carcinogens, with statistically significantly greater reductions being observed with medicinal nicotine.
Comparing Lung Cancer Rates of Men and Women
Results of case–control studies suggest that women may have a higher risk of developing lung cancer than men with equal smoking exposure. However, Bain et al. (p. 826) compared prospective data from the questionnaire-based Nurses’ Health Study of women and the Health Professionals Follow-up Study of men and calculated lung cancer rates of former and current smokers, adjusting for age, cigarettes smoked per day, age at start of smoking, and time since quitting. From 1986 through 2000, 955 and 311 primary lung cancers were identified among the 60,296 women and 25,397 men in the study, respectively, who ranged from 40 to 79 years of age. Lung cancer rates were similar among women and men with similar smoking histories. The authors conclude that both sexes are equally susceptible to lung cancer.
In an editorial (p. 812), Blot and McLaughlin review the increased smoking habits and lung cancer incidence of women over the past 20 years. They note that the findings agree with other large cohort studies and address differences between case–control studies and cohort studies that may lead to conflicting results. In addition, they note that, although men and women with equal smoking histories may be at equal risk of developing lung cancer, identifying the relevant mechanisms may reduce lung cancer incidence in both sexes.
Testing for an Immune Response in Prostate Cancer
Although prostate-specific antigen (PSA) is a prototypic biomarker for prostate cancer, it has poor specificity. Expression of 
-methylacyl-CoA racemase (AMACR), which is involved in modifying branched-chain fatty acids, is specifically increased in prostate cancer epithelia but is not released into the bloodstream at detectable levels. Sreekumar et al. (p. 834) determined whether an immune response to AMACR could be used as a serum biomarker for prostate cancer. The authors found that immunoreactivity against AMACR was higher in sera from patients with prostate cancer than in control subjects. In men with intermediate PSA levels (4–10 ng/mL), the immune response against AMACR was more sensitive and specific than was PSA in distinguishing sera from prostate cancer patients relative to control subjects. The authors conclude that assays to detect a humoral immune response against AMACR may have the potential to supplement PSA screening in identifying patients with clinically significant prostate cancer, especially those with intermediate PSA levels.
In an editorial, Carter and Isaacs (p. 813) stress the need for more biomarkers that are both highly specific for prostate cancer and reflect biologically relevant disease. They see value in proof-of-principle studies that test for an immune response to cancer-specific antigens by using protein microarrays, especially if they lead to improved biomarkers of disease.
Exclusive Pipe Smoking and Mortality
Although it has generally been assumed that pipe smoking, like cigarette and cigar smoking, causes mortality from cancer and other diseases, few studies have examined the adverse health effects of exclusive pipe smoking. Therefore, precise estimates of the risks associated with pipe smoking have been lacking. In this issue, Henley et al. (p. 853) analyzed data on more than 15,000 exclusive pipe smokers (all men) enrolled in the Cancer Prevention Study II, an American Cancer Society prospective cohort study. After 18 years of follow-up, those who smoked pipes at enrollment had an increased risk of death from cancers of the lung, oropharynx, esophagus, colorectum, pancreas, and larynx, compared with never users of tobacco. They also had an increased risk of death from coronary heart disease, cerebrovascular disease, and chronic obstructive pulmonary disease. The risk estimates were generally smaller than those associated with cigarette smoking and similar to or larger than those associated with cigar smoking.
Short Hairpin RNA and Gene Silencing
RNA interference initiated by small interfering RNA effectively but transiently suppresses gene expression, which limits its therapeutic utility. Spänkuch et al. (p. 862) used a xenograft mouse model to determine whether an RNA interference–based strategy that used short hairpin RNAs (shRNAs) to suppress the expression of PLK1, a key cell cycle regulator that is overexpressed in human cancers could inhibit tumor growth. They found that levels of PLK1 mRNA and protein were lower in cancer cells transfected with PLK1 shRNA plasmids than in cancer cells tranfected with control plasmids. When they treated mice with human xenograft tumors systemically with PLK1 shRNA plasmids protected by a nuclease inhibitor, they found that tumor growth was statistically significantly reduced compared with such mice treated with control plasmids. The authors conclude that the combination of shRNA-mediated gene silencing with effective in vivo gene delivery strategies appears to generate a long-lasting gene silencing signal.
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