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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was self-funded by the authors. The authors were responsible for covering all expenses related to the research, data collection, analysis, and publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee of the University of Ibadan/University College Hospital (UI/EC/16/0226) after a review process. Additionally, a written formal informed consent was obtained from all the participants selected. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Our research data is available to all interested parties on the Open Science Framework (OSF) repository, which allows for unrestricted data use. The link to access the dataset is provided below: