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Effect of HMGB1 Polymorphisms on Urothelial Cell Carcinoma Susceptibility and Clinicopathological Characteristics.

ABSTRACT: The high mobility group box 1 gene (HMGB1) plays a prominent role in cancer progression, angiogenesis, invasion, and metastasis. This study explored the effect of HMGB1 polymorphisms on clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 1293 participants (431 patients with UCC and 862 healthy controls) were recruited. Four single-nucleotide polymorphisms (SNPs) of HMGB1 (rs1412125, rs1360485, rs1045411, and rs2249825) were assessed using TaqMan real-time polymerase chain reaction assay. The results indicated that individuals carrying at least one T allele at rs1045411 had a lower risk of UCC than those with the wild-type allele [adjusted odds ratio = 0.722, 95% confidence interval (CI) = 0.565-0.924]. Furthermore, female patients with UCC carrying at least one T allele at rs1045411 were at a lower invasive tumor stage than those with the wild-type allele [odds ratio (OR) = 0.396, 95% CI = 0.169-0.929], similar to nonsmoking patients (OR = 0.607, 95% CI = 0.374-0.985). In conclusion, this is the first report on correlation between HMGB1 polymorphisms and UCC risk. Individuals carrying at least one T allele at rs1045411 are associated with a lower risk of UCC and a less invasive disease in women and nonsmokers.

SUBMITTER: Hung SC

PROVIDER: S-EPMC6299401 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database.MethodsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival.ResultsA total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13-4.90], and smaller tumor (OR 6.63; 95% CI 4.46-9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89-2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86-1.17).ConclusionWe found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC.

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Effect of HMGB1 Polymorphisms on Urothelial Cell Carcinoma Susceptibility and Clinicopathological Characteristics.

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