Ambient air exposures to arsenic and cadmium and overall and prostate cancer–specific survival among prostate cancer cases in Pennsylvania, 2004 to 2014

Abstract

BACKGROUND: Exposures to arsenic (As) and cadmium (Cd) have been associated with higher prostate cancer (PC) mortality; however, these associations have been inconsistent. The authors investigated whether higher ambient air concentrations of As and Cd are associated with lower overall and PC-specific survival among PC cases in Pennsylvania. METHODS: Incident PC cases of patients, aged 40 years or older, with a clinical diagnosis and nonmetastatic disease were identified in the 2004 to 2014 Pennsylvania Cancer Registry. Demographic, clinical, and pathologic information were extracted from the Pennsylvania Cancer Registry. The 3-and 5-year average and cumulative air concentrations of As and Cd were extracted from the Environmental Protection Agency's Toxics Release Inventory database. Spatial-temporal hierarchical accelerated failure time models were used to examine the associations between air concentrations of As and Cd and overall and PC-specific survival for the total population and stratified by geographical region defined by rurality and Appalachia status, after adjusting for confounders. RESULTS: There were 78,914 PC cases included. Increasing 3-and 5-year average and cumulative air concentrations of As and Cd were significantly associated with lower overall and PC-specific survival among cases, after adjusting for confounders, for the total population, and stratified by geographical region for most of the estimates. CONCLUSIONS: Data suggest that increasing ambient air exposures to As and Cd may play a role in overall and PC-specific mortality risk among PC cases. Exposures to As and Cd are modifiable and may provide insight into potential strategies to improve PC health outcomes.

Zinc in Prostate Health and Disease: A Mini Review

“…These authors, also provide a comprehensive review and commentary on Cd-MT toxicology including, the inverse association between Zn-bound MT and Cd-MT, the importance of the Cd/Zn ratio in MT for toxicity manifestation in the kidneys, binding of other metals/metalloids such as Se and bismuth (Bi) to MT in vivo, the four forms of MT 1–4 that have been identified, routes of Cd body entry, long-term Cd exposure favoring Cd storage in MT, biological half-life in humans (10–30 years), minor excretion through urine, ROS effects associated with Cd toxicity, toxicity and toxicokinetic modeling of Cd. Meanwhile, various impacts of Cd on prostate cancer outcomes are known including associations with overall and PC-specific mortality risk and aggressiveness [ 102 , 103 ].…”

“…The major requirement of Zn for prostate health is its ability to truncate the Krebs cycle to prevent citrate oxidation and associated functions [ 47 , 48 ]. However, Zn is also involved in multiple other functions including Zn signaling towards regulating prostate cancer outcomes [ 5 ] accompanied by multiple Zn influx and efflux transporters [ 57 ], storage in MTs [ 102 , 103 ], Zn finger involvement for protein regulation functions [ 119 , 120 ], and Zn coordinated MMP activity that facilitates cancer cell invasion [ 117 ]. A summary of the potential points between Zn ingestion to excretion which may impact prostate cancer outcomes reviewed is given in Figure 2 .…”