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Prognostic significance of HIF‐1α polymorphisms in transitional cell carcinoma of the bladder
Author(s) -
Nadaoka Junichi,
Horikawa Yohei,
Saito Mitsuru,
Kumazawa Teruaki,
Inoue Takamitsu,
Narita Shintaro,
Yuasa Takeshi,
Satoh Shigeru,
Nishiyama Hiroyuki,
Ogawa Osamu,
Tsuchiya Norihiko,
Habuchi Tomonori
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23256
Subject(s) - cystectomy , bladder cancer , transitional cell carcinoma , medicine , single nucleotide polymorphism , allele , hazard ratio , genotype , proportional hazards model , vascular endothelial growth factor , oncology , pathology , carcinoma , gastroenterology , cancer , biology , gene , vegf receptors , genetics , confidence interval
Recently, two single nucleotide polymorphisms in the hypoxia‐inducible factor‐1α ( HIF‐1α ) gene, P582S and A588T , were shown to cause significantly higher transcriptional activity than the wild type. We investigated the association between the HIF‐1α polymorphisms and the incidence and progression of transitional cell carcinoma of the bladder, and the relationship between the polymorphisms and the tissue vascular endothelial growth factor (VEGF) level or microvessel density (MVD). A total of 219 patients with bladder cancer and 464 healthy native Japanese control subjects were enrolled. Tissue VEGF and HIF‐1α expression levels and the mean MVD were evaluated in 73 radical cystectomy specimens by immunohistochemistry. The HIF‐1α genotype did not significantly influence the incidence or disease status of bladder cancer. Among patients who underwent radical cystectomy, those with a variant allele had significantly worse disease‐free survival ( p = 0.001) and disease‐specific survival ( p = 0.006) than those without a variant allele. Multivariate analysis using a Cox proportional hazard model revealed that the presence of a variant allele was an independent predictor of disease‐free survival (HR = 3.10, 95%CI = 1.38–6.99, p = 0.006). Although not statistically significant, the moderate/high expression levels of VEGF in tumor tissues were more frequently observed in patients with a HIF‐1α variant allele (11/13, 84.6%) than in those without (33/60, 55%, p = 0.063). The HIF‐1α polymorphisms may have a significant influence on the poor prognosis of the patients undergoing radical cystectomy for bladder cancer, while they seem to have no relation to the bladder cancer occurrence. © 2007 Wiley‐Liss, Inc.