Association of Cadmium, Lead and Mercury with Paraoxonase 1 Activity in Women

BACKGROUND: The activity of paraoxonase 1 (PON1), an antioxidant enzyme whose polymorphisms have been associated with cancer risk, may be associated with metals exposure. OBJECTIVE: To evaluate PON1 activity in relation to cadmium, lead, and mercury levels in healthy, premenopausal women. METHODS: Women from upstate New York were followed for ≥ two menstrual cycles. Repeated measures linear mixed models estimated the association between cadmium, lead, and mercury levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1 paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R phenotype and un-stratified. RESULTS: Median blood cadmium, lead, and mercury concentrations were 0.30 µg/L, 0.87 µg/dL, and 1.15 µg/L. In un-stratified analyses cadmium and mercury were associated with decreased PON1A activity (T2 vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was associated with decreased PON1A activity for QR and RR phenotypes comparing T2 vs. T1 (−14.4% 95% confidence interval [CI] [−20.1, −8.4] and −27.9% [−39.5, −14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 −18.9% [−32.5, −2.5]; T2 vs. T1 −19.6% [−32.4, −4.4]). Cadmium was associated with lower PON1P comparing T2 vs. T1 for the RR (−34.9% [−51.5, −12.5]) and QR phenotypes (−9.5% [−18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2, 12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 −22.8 [−37.8, −4.1]). CONCLUSION: Blood metals were associated with PON1 activity and these effects varied by phenotype. However, there was not a linear dose-response and these findings await replication.