Association between arsenic levels in toenails and urine and prostate cancer risk: Findings from the MCC-Spain study

BACKGROUND: Arsenic (As) is a toxic metalloid widely distributed in the environment. Chronic exposure to As has been associated with the development of several types of cancer. However, its role in prostate cancer (PC) remains unclear. OBJECTIVE: To evaluate the relationship between As exposure and the risk of PC, considering different clinical tumour classifications and genetic susceptibility, and to compare biomarkers that may reflect distinct exposure windows. METHODS: We included 345 incident cases and 468 controls with available data on both urinary and toenail As concentrations within the MCC-Spain project. Toenail and urinary As levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), respectively. Genetic susceptibility was assessed using a polygenic risk score (PRS) based on Single-Nucleotide Polymorphisms. Associations between As exposure and PC were examined using mixed-effects and multinomial logistic regression models. RESULTS: Higher toenail As concentrations were associated with increased risk of PC [odds ratio (OR) comparing the fourth to first quartile: 1.94; 95 % confidence interval (CI):1.23-3.06]. Stratified analyses by tumor classification showed consistent risk increases for advanced and aggressive tumors [ISUP3-5 Relative risk ratio (RRR) quartile 4vs.1: 2.86 (1.16-7.06); AJCC IIB-IV RRR: 2.58 (1.48-4.50); cT2-cT4 RRR: 3.05 (1.55-5.99)]. No clear association was found with urinary As concentrations. Interaction analyses showed no evidence of effect modification by PRS. CONCLUSION: Elevated toenail As levels were associated with an increased risk of PC, especially in advanced disease, suggesting that toenails represent a more reliable biomarker for assessing long-term As exposure.