High cadmium / zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer.

Tobacco smoke may be one of the most common sources of cadmium (Cd) in the general population, particularly in the rising population of smokers in developing countries. Although a relationship between both cigarette smoking and environmental Cd contamination with prostate cancer exist, the mechanisms are unclear. Most prospective cohort studies found a positive association between current smoking and a fatal cancer of the prostate. We investigated the interaction between zinc and cadmium and the potential risk of prostate cancer in smokers. Serum cadmium level was significantly (P < 0.001) higher in smokers compared with non-smokers, the level in smokers was three-fold that in non-smokers. In contrast zinc was significantly (P < 0.001) reduced in smokers compared with non-smokers. Unlike Zn, Cu was significantly (P < 0.05) higher in smokers than in non-smokers. Iron (Fe) though higher in smokers was not significantly different. Zinc: cadmium ratio was very significantly (P < 0.001) reduced, implying high cadmium: zinc ratio. This ratio was 4.5-fold the level in non-smokers. Total protein, albumin and total globulin levels were all significantly (P < 0.001) reduced in smokers compared with non-smokers respectively. Potassium (K+) was significantly (P < 0.05) higher in smokers than in non-smokers. Magnesium (Mg) was significantly (p < 0.01) reduced in smokers compared to non-smokers. Altered Zn status culminating in high Cd:Zn ratio appears the central factor in smokers; leading to oxidative stress, DNA damage, mutation, impaired DNA repair, P53 expression, angiogenic effect of Cu and impaired vitamin A metabolism. These converge in the risk of the carcinogenic process, suggesting high Cd: Zn ratio as the critical determinant of the risk of prostate cancer in smokers and possibly a biomarker of susceptibility to this environmental disease.