Prostate Specific Antigen Ratio is Negatively Associated with Blood Cadmium Concentration and Smoking Status

Abstract

Smoking is a risk factor for several diseases, notably cardiovascular disease and lung cancer. There is evidence that smoking is associated with an increased risk of prostate cancer, though the mechanisms by and the extent to which smoking may affect prostate cancer risk are unknown. Tobacco smoke contains myriad carcinogens, including cadmium. Cadmium is a toxic transition metal and environmental pollutant found in tobacco, and environmental exposure to cadmium has been associated with greater risk of prostate cancer. We hypothesized that blood cadmium (BCd) would be associated with PSA ratio and that this association would depend on smoking status. We examined the level of prostate specific antigen (PSA), free PSA (fPSA), and fPSA ratio, which better predicts risk of advanced prostate cancer, BCd, and smoking status of 6,007 men in the National Health and Nutrition Examination Survey (NHANES) 2003‐2010. Multiple linear regression was used to predict PSA ratio from BCd, smoking status, age, and ethnicity. Current smokers (CS) were found to have significantly (P < 0.05) lower fPSA and fPSA ratio, and greater BCd compared with non‐smokers (NS) and former smokers (FS) (CS vs. NS: fPSA, 0.31 vs. 0.38 ng/mL; fPSA ratio, 29.1% vs. 31.8%; BCd, 1.30 vs. 0.27 μg/L). Based on the final regression model, BCd was associated with a lower fPSA ratio among CS compared with NS and FS. Compared with NS and FS, for CS a 10% increase in BCd corresponded to a predicted decrease in fPSA ratio of 37% for White and Black men, 54% for Hispanic men, and 217% for other men. These results suggest that smoking is associated with a lower fPSA ratio – and thus potentially greater risk of prostate cancer – and that this effect may be partly attributable to cadmium exposure.Funding: NIH #1R03CA159421‐01A1