Occupational cancer risk surveillance in HIV-infected individuals exposed to chemicals: Role of p53 molecular marker

Abstract

Abstract The growing exposure to occupational chemicals and HIV infection are both major global health issues. However, there is little data on the carcinogenic risk profile of HIV-infected individuals who have been occupationally exposed to chemical mixtures. This study therefore investigated the levels of cancer risk biomarkers in HIV-infected individuals exposed to occupational chemicals, exploring the relationship between apoptotic regulatory markers and DNA oxidative response markers as a measure of cancer risk. Apparently healthy adults (mean age 38.35±0.72years) were divided into four groups according to their HIV status and occupational chemical exposure: 62 HIV positive exposed (HPE), 66 HIV positive unexposed (HPU), 60 HIV negative exposed (HNE), and 60 HIV negative unexposed (HNU). Serum p53, bcl2, 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), and malondialdehyde (MDA) were estimated by standard methods. Blood samples were analysed for CD4 cell count by flow cytometry. Serum p53 and bcl2 levels in HPE (0.91±0.11ng/ml and 122.37±15.77ng/ml) were significantly lower than HNU (1.49±0.15ng/ml and 225.52±33.67ng/ml) (p < 0.05), respectively. Wildtype p53 and bcl2 were positively and significantly correlated with 8-OHdG (r=0.35, p<0.001; r=0.36, p<0.001) and SOD (r=0.38, p<0.001; r=0.39, p<0.001). After controlling for gender, age, BMI, and cigarette smoking, both HIV status and SOD activity were significantly associated with wildtype p53 and bcl2 (p < 0.05). Malondialdehyde was significantly higher in the HPE (0.72 ± 0.01 mg/ml) than in the HNE (0.68 ± 0.01 mg/ml) and HNU (0.67 ± 0.01 mg/ml) groups (p < 0.05). Additionally, the HPE group (578.87±33.64 cells/µL) exhibited significantly lower CD4 counts than the HNE (785.35±36.8 cells/µL) and HNU (862.15±43.29 cells/µL) groups. Individuals infected with HIV and occupationally exposed to chemical substances exhibit compromised immunity, elevated oxidative stress, and depressed p53 (loss of tumour suppressive capacity) and bcl2; a convergence promoting the carcinogenic pathway and elevated cancer risk. These findings provide a mechanistic basis of cancer risk and scientific justification for preventive strategies against carcinogenesis in individuals who are HIV-infected.