Middle-aged men who are long-term, heavy smokers have twice the risk of developing more aggressive forms of prostate cancer than men who have never smoked, according to an article in the July issue of Cancer Epidemiology, Biomarkers and Prevention.

Specifically, men under age 65 years with a history of 40 or more pack-years (the equivalent of at least 1 pack/day for 40 years or 2 packs/day for 20 years) face a 100 percent increase in risk for development of more aggressive prostate cancer than that found in nonsmokers, according to senior author Janet L. Stanford, Ph.D.

The same population of men with a significant smoking history has a 60 percent increase in risk for prostate cancer compared with nonsmokers, and men who are current smokers have a 40 percent increase in risk for prostate cancer.

The study involved more than 1,450 men aged 40 to 64 years from a single urban area. Half had a history of prostate cancer and the other half, which did not have such a history, 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 years, 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.

A second 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.

"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 Janet L. Stanford, Ph.D., senior author of the article.

Stanford noted that earlier research results on smoking and prostate cancer had yielded mixed results. However, she believes that the current findings in combination with recent work from two other American universities (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.

Smoking may promote prostate cancer through several mechanisms. It can increase the circulating level of androgens, which are stimulatory to prostate cancer cells. It is also possible that smoking contributes to cancer risk through body exposure to the heavy metal cadmium, which has been linked to prostate cancer in occupational-health studies and is known to act as a carcinogen through interference with DNA repair.

Stanford also noted a positive finding for smokers and their physicians: Although the relative risk for prostate cancer increases with the number of pack-years smoked, this risk declines to near that of nonsmokers within about 10 years of quitting.