Photo Credit: Naeblys
The following is a summary of “CTLA4 genetic variants associated with urothelial bladder cancer susceptibility,” published in the June 2024 issue of Urology by Koike et al.
This study explored the association between CTLA4 genetic variants, specifically rs231775 (+49A>G) and rs231779 (+1822C>T), and their impact on susceptibility, stage, prognosis, and treatment response in patients with urothelial bladder cancer (UBC). A total of 140 patients with UBC and 145 controls were enrolled. The patients were categorized into subgroups, including non-muscle invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), metastasis, recurrence, and varying risk levels (low, moderate, high, very high). Comprehensive demographic, anthropometric, epidemiological, and clinical data were collected from all participants using a structured questionnaire. The CTLA4 variants were genotyped using real-time polymerase chain reaction (qPCR), and the genotypes were analyzed across multiple genetic models: allelic, codominant, dominant, recessive, and over-dominant.
Results revealed that patients with UBC were generally older and predominantly smokers (P < 0.001) compared to controls. Additionally, patients with UBC exhibited higher waist circumference and elevated systolic and diastolic blood pressure (P = 0.005, P = 0.006, and P < 0.001, respectively). Notably, a protective effect against UBC was observed in individuals carrying the heterozygous genotypes of CTLA4 rs231775 (odds ratio [OR] = 0.40; 95% CI: 0.16-0.98, P = 0.045) and rs231779 (OR = 0.35; 95% CI: 0.14-0.87, P = 0.024). Nagelkerke R2 analysis demonstrated that models incorporating age and smoking status alongside the CTLA4 rs231775 variant explained 77.0% of UBC susceptibility. Similarly, a model including age, smoking, and the CTLA4 rs231779 variant explained 77.2% of UBC susceptibility.
In conclusion, the study identified the CTLA4 rs231775 AG and rs231779 CT heterozygous genotypes as potential protective factors in the overdominant model when combined with age and smoking status. These findings suggest that these genetic variants and age and smoking habits may serve as valuable biomarkers for assessing susceptibility to UBC. Integrating these biomarkers into clinical practice could enhance early detection and personalized treatment strategies for patients with UBC.
Source: sciencedirect.com/science/article/abs/pii/S1078143924004903
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