Effect of CD44 gene polymorphisms on risk of transitional cell carcinoma of the urinary bladder in Taiwan
The carcinogenesis of transitional cell carcinoma (TCC) of the urinary bladder involves etiological factors, such as ethnicity, the environment, genetics, and diet. Cluster of differentiation (CD44), a well-known tumor marker, plays a crucial role in regulating tumor cell differentiation and metastasis. This study investigated the effect of CD44 single nucleotide polymorphisms (SNPs) on TCC risk and clinicopathological characteristics. Five SNPs of CD44 were analyzed through real-time polymerase chain reaction in 275 patients with TCC and 275 participants without cancer. In this study, we observed that CD44 rs187115 polymorphism carriers with the genotype of at least one G were associated with TCC risk. Furthermore, TCC patients who carried at least one G allele at CD44 rs187115 had a higher stage risk than did patients carrying the wild-type allele (p < 0.05). In addition, The AATAC or GACGC haplotype among the five CD44 sites was also associated with a reduced risk of TCC. In conclusion, our results suggest that CD44 SNPs influence the risk of TCC. Patients with CD44 rs187115 variant genotypes (AG + GG) exhibited a higher risk of TCC; these patients may possess chemoresistance to developing late-stage TCC compared with those with the wild-type genotype. The CD44 rs187115 SNP may predict poor prognosis in patients with TCC.
KeywordsSingle nucleotide polymorphism CD44 Transitional cell carcinoma
This study was supported by a research grant from Chung Shan Medical University and Tungs’ Taichung Metro Harbor Hospital (CSMU-TTM-103-01).
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Conflicts of interest
- 5.Kellen E, Zeegers M, Paulussen A, Vlietinck R, Vlem EV, Veulemans H, et al. Does occupational exposure to pahs, diesel and aromatic amines interact with smoking and metabolic genetic polymorphisms to increase the risk on bladder cancer?; The belgian case control study on bladder cancer risk. Cancer Lett. 2007;245:51–60.Google Scholar
- 7.Pow-Sang JM, Seigne JD. Contemporary management of superficial bladder cancer. Cancer Control: J Moffitt Cancer Cent. 2000;7:335–9.Google Scholar
- 19.Ioachim E, Charchanti A, Stavropoulos N, Athanassiou E, Bafa M, Agnantis NJ. Expression of cathepsin D in urothelial carcinoma of the urinary bladder: an immunohistochemical study including correlations with extracellular matrix components, CD44, p53, Rb, c-erbB-2 and the proliferation indices. Anticancer Res. 2002;22:3383–8.PubMedGoogle Scholar
- 41.Kuniyasu H, Oue N, Tsutsumi M, Tahara E, Yasui W. Heparan sulfate enhances invasion by human colon carcinoma cell lines through expression of CD44 variant exon 3. Clin Cancer Res: Off J Am Assoc Cancer Res. 2001;7:4067–72.Google Scholar
- 42.Miyoshi T, Kondo K, Hino N, Uyama T, Monden Y. The expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 1997;3:1289–97.Google Scholar
- 51.Kuncova J, Kostrouch Z, Viale M, Revoltella R, Mandys V. Expression of CD44v6 correlates with cell proliferation and cellular atypia in urothelial carcinoma cell lines 5637 and HT1197. Folia Biol. 2005;51:3–11.Google Scholar
- 53.Hofmann M, Rudy W, Gunthert U, Zimmer SG, Zawadzki V, Zoller M, et al. A link between ras and metastatic behavior of tumor cells: ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells. Cancer Res. 1993;53:1516–21.PubMedGoogle Scholar