Impact of RAGE polymorphisms on urothelial cell carcinoma clinicopathologic characteristics and long-term survival

Objectives: Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract that is associated with environmental factors and genetic effects. Receptor for advanced glycosylation endproducts (RAGE) plays a vital role in chronic inflammation and tumorigenesis. This study explored the impact of RAGE gene polymorphisms on the clinicopathological status and prognosis of patients with UCC.

Materials and methods: A total of 1,023 participants, including 431 patients with UCC and 592 healthy controls, were recruited for this study. Four polymorphisms of the RAGE gene, including -429T>C (rs1800625), -374T>A (rs1800624), Gly82Ser (rs2070600), and 1704G>T (rs184003), were examined using a real-time polymerase chain reaction with the TaqMan assay.

Results: We found that individuals carrying at least 1 C allele at RAGE rs1800625 had a higher risk of developing UCC than those carrying a wild-type allele. Subgroup analysis revealed that among UCC patients aged younger than 65 years, those with a C allele at rs1800625 had a higher incidence of muscle invasive tumor and lymph node invasion. With a median follow-up of 39 months, TT polymorphisms of rs184003 were associated with worse disease-specific survival (HR = 7.58, 95% CI = 2.52-22.77, P < 0.001) and all-cause survival (HR = 6.45, 95% CI = 2.19-19.034, P < 0.001) in UCC patients aged younger than 65 years.

Conclusion: This study is the first to report a correlation between RAGE polymorphisms and UCC risk. Individuals that carry at least 1 C allele at rs1800625 of RAGE are associated with a higher risk of UCC development, particularly if they belong to the categories previously identified. TT polymorphism at rs184003 is associated with worse disease-specific survival and overall survival in people aged ≤65 years.