The International Agency for Research on Cancer reported that some chemicals in hair dyes are probably carcinogenic to those exposed to them occupationally. Biological mechanisms through which hair dye use may be related to human metabolism and cancer risk are not well-established. We conducted the first serum metabolomic examination comparing hair dye users and nonusers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Metabolite assays were conducted using ultrahigh performance liquid chromatography-tandem mass spectrometry. The association between metabolite levels and hair dye use was estimated using linear regression, adjusting for age, body mass index, smoking, and multiple comparisons. Among the 1,401 detected metabolites, 11 compounds differed significantly between the two groups, including four amino acids and three xenobiotics. Redox-related glutathione metabolism was heavily represented, with L-cysteinylglycine disulfide showing the strongest association with hair dye (effect size (β) = - 0.263; FDR adjusted p-value = 0.0311), along with cysteineglutathione disulfide (β = - 0.685; FDR adjusted p-value = 0.0312). 5alpha-Androstan-3alpha,17beta-diol disulfate was reduced in hair dye users (β = - 0.492; FDR adjusted p-value = 0.077). Several compounds related to antioxidation/ROS and other pathways differed significantly between hair dye users and nonusers, including metabolites previously associated with prostate cancer. Our findings suggest possible biological mechanisms through which the use of hair dye could be associated with human metabolism and cancer risk.
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