Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer

• Published in: Environmental science & technology Vol. 55; no. 14; pp. 9926 - 9937
• Main Authors: Mustieles, Vicente, Pérez-Carrascosa, Francisco M, León, Josefa, Lange, Theis, Bonde, Jens-Peter, Gómez-Peña, Celia, Artacho-Cordón, Francisco, Barrios-Rodríguez, Rocío, Olmedo-Requena, Rocío, Expósito, José, Jiménez-Moleón, José J, Arrebola, Juan P
• Format: Journal Article
• Language: English
• Published: Easton American Chemical Society 20.07.2021
• Subjects: Adipose tissue; Body fat; Cancer; Carcinogenesis; Carcinogens; confidence interval; Confidence intervals; Ecotoxicology and Public Health; Glutathione; Glutathione reductase; glutathione-disulfide reductase; hazard ratio; Health risks; Hexachlorobenzene; Hexachlorocyclohexane; humans; Microenvironments; Oxidative stress; PCB; Persistent organic pollutants; Pollutants; Polychlorinated biphenyls; Reductases; Regression analysis; Regression models; Risk; Spain; Statistical analysis; Superoxide dismutase; Tumors; Spain; persistent organic pollutants; organochlorine pesticides; cancer; polychlorinated biphenyls; oxidative stress
• ISSN: 0013-936X; 1520-5851; 1520-5851
• DOI: 10.1021/acs.est.0c08180

We aimed to assess the relationships among the adipose tissue’s (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003–2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), β-hexachlorocyclohexane (β-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between β-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT’s oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies.