Genetic variants in 8-oxoguanine DNA glycosylase 1 ( <i>OGG1</i> ) and X-ray repair cross-complementing protein 1 ( <i>XRCC1</i> ) and non-genetic factors are associated with bladder cancer susceptibility and prognosis in a Brazilian population

Cellular responses to DNA damage play a crucial role in carcinogenesis, particularly in environmentally related cancers such as bladder cancer (BC). This is the ninth most frequently occurring cancer globally and most frequent in the urinary system. Polymorphic variants in genes encoding DNA repair proteins may interfere with their expression and/or activity. Consequently, modulation in an individual's gene response to exposure might occur resulting in greater susceptibility and lower survival rates in BC. Taking this into account, the study evaluated associations of single-nucleotide polymorphisms (SNPs) in base excision repair genes (<i>XRCC1</i> rs25487 and <i>OGG1</i> rs1052133) with BC susceptibility and prognosis. A total of 274 cases and 274 controls, matched on gender, age, and smoking status, were genotyped using DNA from peripheral blood. In susceptibility analyses, individuals with a family history of cancer who carried at least one reference allele (rs1052133, CC + CG) exhibited an increased risk of BC occurrence. For <i>XRCC1</i>, the TT + CC genotypes were associated with elevated risk for BC among pesticide-exposed individuals. Regarding prognosis, the rs1052133 CC genotype was associated with an enhanced risk of recurrence among smokers and female patients. Bioinformatic analyses indicated significantly higher expression of <i>XRCC1</i> and <i>OGG1</i> in bladder tissue and marked elevation in expression in tumors. These results suggest that gene-environment interaction might modulate risk of BC occurrence and subsequent prognosis.