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...

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Bibliographic Details
Authors: Varea-Jiménez, Elena, Pastor-Barriuso, Roberto, Sierra, Maria Angeles, Dierssen-Sotos, Trinidad, Fernández Tardón, Guillermo, Aragonés, Nuria, Gómez-Acebo, Inés, Castaño-Vinyals, Gemma, Gómez-Ariza, Jose Luis, Kogevinas, Manolis, Moreno, Víctor, Fernández-Navarro, Pablo, Pollan-Santamaria, Marina, Perez-Gomez, Beatriz, García-Esquinas, Esther
Format: article
Publication Date:2026
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/27170
Online Access:https://hdl.handle.net/20.500.12105/27170
Access Level:Open access
Keyword:Biomarkers
Exposure
Genetic susceptibility
Prostate cancer
Toenails arsenic
Urine arsenic
Description
Summary: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.