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Preliminary evidence of polymorphisms of cell cycle regulatory genes and their roles in urinary tract urothelial cancer susceptibility and prognosis in a Taiwan population
Authors:Ying-Chu Lin  Tzyh-Chyuan Hour  Yu-Chieh Tsai  Shu-Pin Huang  Wen-Jeng Wu  Chung-Hsin Chen  Yeong-Shiau Pu  Shiu-Dong Chung  Chao-Yuan Huang
Affiliation:1. School of Dentistry, Kaohsiung Medical University, Kaohsiung City, Taiwan;2. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan;3. Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan;4. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;5. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei City, Taiwan;6. Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan;g. School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan;h. Department of Urology, National Taiwan University Hospital, Hsin Chu Branch, Hsin Chu City, Taiwan
Abstract:

Objective

Our aims were to investigate the correlations between polymorphisms in the cell cycle regulatory genes (aurora kinase A [AURKA], survivin, p21, and p53) and UC risk and prognosis.

Patients and methods

This study recruited 185 patients with UTUC, 46 patients with bladder cancer, and 188 hospital controls. Demographic data and possible confounding factors were collected using a standardized questionnaire. Genotyping was determined by real-time polymerase chain reaction and TaqMan probe methods.

Results

Compared to the UTUC group, the control group had significantly more alcohol drinkers and coffee drinkers but not cigarette smokers. Statistical analyses showed that UTUC risk correlated with AURKA rs2273535 (adjusted odds ratio = 2.51, 95% CI = 1.07–6.15) and with survivin rs9904341 (adjusted odds ratio = 1.82, 95% CI = 1.03–3.26) polymorphisms but not with p21 and p53 polymorphisms. The bladder cancer risk showed no significant correlations with the 4 polymorphisms. In both the UTUC and UC groups, disease-free survival and overall survival were significantly longer in patients with the rs1801270CC genotype compared to those with CA+AA genotypes. Poor prognosis did not correlate with polymorphisms in AURKA, survivin, and p53 genes.

Conclusion

These results suggest that cell cycle regulatory gene polymorphisms rs2273535 and rs9904341 may contribute to UTUC susceptibility; gene polymorphism rs1801270 may contribute to prognosis of UTUC and prognosis of UC. The p53 polymorphisms may not correlate with UTUC susceptibility and prognosis of UTUC or UC. Further well-designed, large-scale studies are needed to clarify these findings.
Keywords:Aurora kinase A  Polymorphism  p21  p53  Susceptibility  Survivin  Urinary tract urothelial cancer
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