Toenail arsenic species and metallome profiles associated with breast, cervical, prostate, and skin cancer prevalence in the Atlantic Partnership for Tomorrow's Health cohort.

Introduction: Chronic exposure to arsenic through drinking water has been linked to several cancers. The metabolism of arsenic is thought to play a key role in arsenic-related carcinogenesis as metabolites of varying toxicity are produced and either stored in or excreted from the body. Atlantic Canada has the highest age-standardized incidence rates of all cancers in the country. This may be due to its high levels of environmental arsenic and the prevalence of unregulated private wells for water consumption. Here, we aimed to characterize the profiles of arsenic species and metallome in the toenails of four cancer groups, compare them to healthy participants (N = 338), and assess potential associations between the profiles with cancer prevalence. Methods: This study employed a case-control design. Toenail samples and questionnaire data from cases (breast, cervical, prostate, and skin cancers) and controls were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. The levels of arsenic species were measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) paired with High Performance Liquid Chromatography (HPLC) and total concentrations of metallome (23 metals) were determined by ICP-MS separately. Multivariate analyses were conducted to compare cases with controls within each cancer group. Results: Arsenic speciation profiles varied by cancer type and were significantly different between cases and controls in the breast (p = 0.0330), cervical (p = 0.0228), and skin (p = 0.0228) cancer groups. In addition, the profiles of metallome (nine metals) were significantly differentiated in the prostate (p = 0.0244) and skin (p = 0.0321) cancer groups, with higher zinc concentrations among cases compared to controls. Conclusion: History of cancer diagnosis was associated with specific profiles of arsenic species and metallome. Our results indicate that arsenic methylation and zinc levels, as measured in toenails, may be an important biomarker for cancer prevalence. Further research is needed to use toenails as a prognostic measure of arsenic-and other metal-induced cancer.

Arsenic Speciation and Metallomics Profiling of Human Toenails as a Biomarker to Assess Prostate Cancer Cases: Atlantic PATH Cohort Study.

Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.