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14 July 2003
Heavy Smoking Doubles Risk Of Aggressive Prostate Cancer
by George Atkinson

Middle-aged men who are long-term, heavy smokers face twice the risk of developing more aggressive forms of prostate cancer than men who have never smoked, according to new findings from Fred Hutchinson Cancer Research Center appearing in the July issue of Cancer Epidemiology, Biomarkers and Prevention. Specifically, men under age 65 with a history of 40 or more "pack-years" (those who smoke a pack a day for 40 years or two packs a day for 20 years) of cigarette smoking face a 100 percent increased risk - or double the risk - of developing more aggressive forms of the disease as compared to nonsmokers, according to senior author Janet L. Stanford, Ph.D., and colleagues in Fred Hutchinson's Public Health Sciences Division. Such men with heavy smoking exposure also face a 60 percent increased risk of prostate cancer overall relative to nonsmokers. Compared to nonsmokers, current smokers experienced a 40 percent increase in the risk of prostate cancer.

Researchers from the University of Washington School of Medicine also collaborated on the study, which was funded by the National Cancer Institute.

"This study provides additional evidence that supports a role for smoking as a risk factor for prostate cancer and confirms recent findings that suggest smoking is an even stronger risk factor for more life-threatening forms of prostate cancer," said Stanford, director of Fred Hutchinson's Prostate Cancer Research Program.

Previously, research results regarding smoking and prostate cancer have been mixed, but these results, together with recent findings from investigators at Johns Hopkins University and Harvard University, provide cumulative evidence that smoking - in particular high-dose, long-term cigarette exposure - is an important risk factor for prostate cancer, said Stanford, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

"From a public-health perspective, I think we now have enough evidence to suggest that prostate cancer should be added to the long list of malignancies in which smoking plays a role," she said. Other smoking-related cancers include those of the lung, bladder, cervix, esophagus and kidney.

The study involved more than 1,450 Seattle-area men, ages 40 to 64. Half had a history of prostate cancer (diagnosed between 1993 and 1996) and the other half, which did not have a history of prostate cancer, served as a comparison group. Participants completed detailed in-person interviews that assessed a variety of factors, from smoking and alcohol consumption to diet and occupational history.

One of the study's strengths is that it focused on younger men who have a lower overall incidence of prostate cancer, which may have enhanced the researchers' ability to tease out the effects of specific risk factors.

"The contribution of smoking to prostate cancer may have been easier to detect in men under 65, who are at lower absolute risk of the disease, than in older men, in whom the cumulative effects of numerous risk factors may cloud the picture," Stanford said.

Another strength of the study is that it assessed other lifestyle variables - from prostate-cancer screening history to dietary intake - factors which, if unaccounted for during data analysis, might have biased the results.

Smoking may promote prostate cancer through several mechanisms. One is that it can increase the amount of circulating androgens, which fuel the growth of normal and malignant prostate cells.

"Cigarette smoking appears to alter a man's hormonal milieu by tilting the scale toward a hormonal environment that may be conducive to tumor growth," Stanford said.

Another theory is related to tobacco as a source of cadmium, a heavy metal that has been linked to prostate cancer in several occupational-health studies. This known human carcinogen inhibits DNA repair, which allows cancer cells to mutate and multiply.

"Cadmium has been shown to be concentrated in the prostate, so this may be one chemical exposure from cigarette smoking that could have an adverse biological effect on the prostate," Stanford said.

One positive finding, however, is that while the relative risk of developing prostate cancer increases with the number of pack-years smoked, this risk declines to near that of nonsmokers within about 10 years of quitting, Stanford said.

"When men stop smoking, within a decade their risk of prostate cancer returns to a level that is not substantially different from nonsmokers, so for most men, it's not too late to quit. There are few environmental risk factors for prostate cancer that have been identified, but here's one way that men can take action to reduce their risk," she said.

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