PHILADELPHIA, PA. (American Association for Cancer Research) -- Former smokers with high quantities of selenium in their toenails experienced half as many bladder tumors as their counterparts with low amounts of the element, according to a study published in the November issue of the American Association for Cancer Research's journal Cancer Epidemiology Biomarkers & Prevention.

By comparison, the study found that selenium - present in certain foods and supplements -- appeared to have little or no effect on non-smokers or current smokers. A possible explanation, the scientists suggest, is the element's reputed anti-oxidant activity.

"The lack of effect of selenium status among non-smokers is consistent with this hypothesis, since those who never smoked have not been exposed to smoking induced oxidative stress," said Maurice P.A. Zeegers, an assistant professor of epidemiology at Maastricht University in the Netherlands, and the study's lead author.

Also participating in the study, titled "Prediagnostic Toenail Selenium and Risk of Bladder Cancer," are Alexandra Goldbohm, with the Department of Nutritional Epidemiology at TNO Nutrition and Food Research, Zeist, the Netherlands; Peter Bode, with the Interfaculty Reactor Institute, Delft University of Technology; and Peit van den Brandt, also with the Department of Epidemiology, Maastricht Univerity, in Maastricht.

Bladder cancer is the most common cancer of the urinary tract and is the seventh most common cancer among men, accounting for about 200,000 new cases per year worldwide. Over the last four decades, many epidemiological studies and several reviews have suggested that bladder cancer is linked to environmental factors, including cigarette smoking, diet, fluid consumption, shistosomal infections and exposures to industrial chemicals.

Past research has suggested that diets rich in selenium result in lower incidences of cancer, particularly lung, colorectal and prostate cancers.

The most important dietary sources of selenium are meats, fish, cereal, dairy products and eggs. Some nuts, particularly Brazil nuts, contain high quantities of this element.

This latest study, supported by the Dutch Cancer Society, represents the largest and most definitive evidence that selenium intake may help prevent bladder cancer in both men and women, particularly among former smokers.

Study participants included some 120,852 men and women living in the Netherlands, including 431 with bladder cancer, enrolled in a larger population-based prospective study on diet and cancer. Each participant was asked to complete a questionnaire on risk factors for cancer -- including diet, exposure to industrial chemicals, and smoking history - and to provide toenail clippings to detect trace quantities of selenium.

"A selenium marker should preferably reflect long-term selenium intake," said Dr. Zeegers. "For this reason, we used levels of selenium in toenails to assess selenium intake instead of serum selenium, a short-term marker of selenium intake.

"Available evidence suggests that selenium levels in toenails reflect intake integrated for the previous 12 months or longer."

Results of this prospective study showed that men and women in groups with the highest quantities of selenium in their toenails -- at least 30 percent higher than the lowest quantities of selenium -- experienced slightly fewer cases of bladder cancers.

However, the biggest impact was seen among former smokers. No other factor, including other known anti-oxidants including Vitamin C, E and beta-carotene, lowered the incidence of bladder cancer in the study groups. What's more, the association was mainly confined to invasive carcinomas of the bladder. It's been recently suggested that urinary bladder cancer might be divided into two separate diseases: non-invasive and invasive. In addition to different prognostic and pathogenic properties, these two diseases appear to result from diverse molecular events.

"Further research is needed to evaluate the influence of selenium on one of bladder cancers, the invasive form, when compared to the non-invasive form," said Dr. Zeegers.