Environmental and lifestyle factors in epigenetic regulation of bladder cancer: Impact on CALCA and CCNA1 gene methylation

Abstract

Requirement for non-invasive biomarkers is emerging, which can decipher lifestyle exposures to epigenetic alterations in bladder cancer due to high recurrence of the disease, and currently used tests like urine cytology with low sensitivity for such tumours. There is a high influence of lifestyle and environmental factors on Urinary bladder cancer (UBC), particularly smoking and chemical exposures. This study evaluates the methylation status of CALCA and CCNA1 genes in UBC patients. It also examines their association with smoking and occupational chemical exposure. A case-control study was conducted with 89 patients with bladder cancer and 80 healthy controls. Methylation-specific PCR (MS-PCR) was used to assess promoter methylation in blood and tissue specimens. Associations of UBC with risk factors, recurrence, and clinicopathological features were studied. The results reflect hypermethylation of the CALCA and CCNA1 genes in UBC cases (66.2% and 53.9%) as compared to controls (1.25% and 2.5%, P< 0.0001). In our study, smoking has been correlated with methylation of CALCA (P= 0.0001) and CCNA1 (P= 0.0038)genes , whereas chemical exposure associated the CCNA1 gene methylation (P< 0.0005) with a major link with recurrence. Gene Methylation associations were not found with age, gender, or tumour grade. These findings point out that environmental factors influence CALCA and CCNA1 methylation in the development of urinary bladder cancer. Additionally, CCNA1 methylation may serve as a biomarker for recurrence, emphasising the importance of epigenetic monitoring in high-risk populations. Taken together, these data support methylation-based, minimally invasive risk assessment in high-risk groups (smokers and occupationally exposed workers) and recurrence surveillance to complement cystoscopy in routine follow-up.