TY - JOUR
T1 - Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer
AU - Mustieles, Vicente
AU - Perez-Carrascosa, Francisco M.
AU - Leon, Josefa
AU - Lange, Theis
AU - Bonde, Jens-Peter
AU - Gomez-Pena, Celia
AU - Artacho-Cordon, Francisco
AU - Barrios-Rodriguez, Rocio
AU - Olmedo-Requena, Rocio
AU - Exposito, Jose
AU - Jimenez-Moleon, Jose J.
AU - Arrebola, Juan P.
PY - 2021
Y1 - 2021
N2 - 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), beta-hexachlorocyclohexane (beta-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 beta-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.
AB - 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), beta-hexachlorocyclohexane (beta-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 beta-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.
KW - oxidative stress
KW - persistent organic pollutants
KW - organochlorine pesticides
KW - polychlorinated biphenyls
KW - cancer
KW - POLYCHLORINATED-BIPHENYLS
KW - OXIDATIVE STRESS
KW - ADULT COHORT
KW - ORGANOCHLORINE PESTICIDES
KW - CHRONIC EXPOSURE
KW - PROSTATE-CANCER
KW - BREAST-CANCER
KW - SERUM CONCENTRATIONS
KW - COLORECTAL-CANCER
KW - DNA-ADDUCTS
U2 - 10.1021/acs.est.0c08180
DO - 10.1021/acs.est.0c08180
M3 - Journal article
C2 - 34180659
VL - 55
SP - 9926
EP - 9937
JO - Environmental Science & Technology
JF - Environmental Science & Technology
SN - 0013-936X
IS - 14
ER -