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Differential Gene Expression in Bladder Tumors from Workers Occupationally Exposed to Arylamines

ABSTRACT: Occupational exposure to the arylamines benzidine and β-naphthylamine increase bladder cancer risk up to 100-fold, making them some of the most powerful human carcinogens. We hypothesize that tumors arising in people with occupational exposures have different patterns of gene expression than histologically similar tumors from people without such exposures. In a case-case study, we compare gene expression in 22 formalin-fixed paraffin-embedded (FFPE) bladder tumors from men with high-level occupational exposure to arylamines to that in 26 FFPE bladder tumors from men without such exposure. Gene expression analysis was performed on the NanoString nCounter system using a PanCancer Progression Panel comprised of 740 cancer progression-related genes and a custom panel of 69 arylamine- and bladder cancer-related genes which were chosen from in vitro studies. Although fold differences were small, there was evidence of differential expression by exposure status for 17 genes from the Progression Panel and 4 genes from the custom panel. In total, 10 genes showed dose-response association at a p < 0.01, of which 4 genes (CD46, NR4A1, BAX, and YWHAZ) passed a false discovery rate (FDR) q value cutoff of 0.05 but were not significant after Bonferroni correction. Overall, we find limited evidence for differentially expressed genes in pathways related to DNA damage signaling and epithelial-to-mesenchymal transition (EMT).

SUBMITTER: Kolli R

PROVIDER: S-EPMC8592720 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveWorkers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms.MethodsThis study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes' polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected.ResultsThere was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels.ConclusionTherefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk.

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Differential Gene Expression in Bladder Tumors from Workers Occupationally Exposed to Arylamines

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