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. 2022 Jul 7:10:818069.
doi: 10.3389/fpubh.2022.818069. eCollection 2022.

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

Erin Keltie  1   2 , Kalli M Hood  1   2 , Yunsong Cui  3 , Ellen Sweeney  3 , Gabriela Ilie  1 , Anil Adisesh  4   5 , Trevor Dummer  6 , Veni Bharti  1   2 , Jong Sung Kim  1   2
Affiliations

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

Erin Keltie et al. Front Public Health. .

Abstract

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.

Keywords: arsenic exposure; cohort study; metallome; prostate cancer; speciation; toenail biomarker.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the approach and methods used in this study.
Figure 2
Figure 2
Mean toenail arsenic species in prostate cancer cases (n = 139) and controls (n = 400) and correlation with total arsenic. Asterisks indicate the statistical significance of the mean difference between prostate cancer cases and healthy controls; * indicates p < 0.01. Error bars indicate 95% CI. r = Pearson correlation coefficient associated with the correlation between arsenic species and total arsenic. p = p-value associated with Pearson correlation coefficient.
Figure 3
Figure 3
Mean urine arsenic species of prostate cancer cases (n = 38) and controls (n = 114) and correlation with total arsenic adjusted to urinary creatinine concentration. Error bars indicate 95% CI. r = Pearson correlation coefficient associated with the correlation between arsenic species and total arsenic expressed as μg As per g urinary creatinine. p = p-value associated with Pearson correlation coefficient.
Figure 4
Figure 4
Mean metallome concentrations in toenail and urine samples. Circles indicate crude means from MANOVA models and triangles indicate adjusted means from MANCOVA models. Error bars indicate standard error.
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