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Polymorphisms in Inflammation Genes and Bladder Cancer: From Initiation to Recurrence, Progression, and Survival

From the Departments of Epidemiology, Urology, Genitourinary-Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and the Scott Department of Urology, Baylor College of Medicine, Houston TX

Address reprint requests to Xifeng Wu, MD, PhD, Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1155 Pressler Blvd, Houston, TX 77030; e-mail: xwu{at}mdanderson.org

PURPOSE: Since chronic inflammation contributes to tumorigenesis, we hypothesized that the risk and clinical outcome of bladder cancer (BC) might be modulated by genetic variations in inflammation genes.

METHODS: Using the TaqMan method, we genotyped single nucleotide polymorphisms in interleukin (IL) -6 (–174 GC), IL-8 (–251 TA), tumor necrosis factor-alpha (TNF-; –308 GA), and peroxisome proliferator-activated receptor (PPARG; Pro12Ala), and determined their associations with BC initiation and clinical outcome.

RESULTS: We found that the IL-6 variant genotype (C/C) was associated with an increased BC risk (OR, 1.77; 95% CI, 1.25 to 2.51). There were joint effects between the variant IL-6 genotypes and smoking status, and between the variant genotypes of IL-6 and other genes. To assess effect on recurrence, we grouped non-muscle-invasive BC patients according to intravesical Bacillus Calmette-Guerin (BCG) treatment status: no BCG, induction BCG (iBCG), and maintenance BCG (mBCG). In the Cox proportional hazards model, the variant IL-6 genotype was associated with an increased recurrence risk (hazard ratio [HR], 4.60; 95% CI, 1.24 to 17.09) in patients receiving mBCG. The variant PPARG genotype was associated with a reduced recurrence risk (HR, 0.41; 95% CI, 0.20 to 0.86) among untreated patients. In patients with non-muscle-invasive BC, the variant IL-6 genotype was associated with an increased progression risk (HR, 1.88; 95% CI, 0.80 to 4.11). In patients with invasive BC, variant IL-6 was associated with improved 5-year overall and disease-specific survival (HR, 0.43; 95% CI, 0.19 to 0.94 and HR, 0.39; 95% CI, 0.15 to 1.00, respectively).

CONCLUSION: Inflammation gene polymorphisms are associated with modified BC risk, treatment response, and survival.

Supported by grant Nos. CA74880 and CA91846 from the National Cancer Institute, and a fellowship from the American Physician Fellowship Organization (D.L.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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