Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis

Lin, Hung-Yu; Yang, Ming-Chang; Huang, Chun-Hsiung; Wu, Wen-Jen; Yu, Tsan-Jung; Lung, For-Wey

doi:10.1016/j.urolonc.2011.11.031

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Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis

Hung-Yu Lin, M.D., M.S.
- Department of Urology, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Ming-Chang Yang, M.S.
- Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
- Institute of Biological Science, National Sun Yat-sen University, Kaohsiung City, Taiwan
Chun-Hsiung Huang, M.D.
- Department of Urology, Kaohsiung Medical University, Kaohsiung, Taiwan
Wen-Jen Wu, M.D.
- Department of Urology, Kaohsiung Medical University, Kaohsiung, Taiwan
Tsan-Jung Yu, M.D.
- Department of Urology, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan
For-Wey Lung, M.D., Sc.D.
- Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
- National Defense Medical Center, Taipei, Taiwan
- Corresponding author. Tel.: +886-2-2726-3141; fax: +886-2-2728-5059.

Received 21 September 2011; received in revised form 9 November 2011; accepted 15 November 2011. published online 19 December 2011.
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Abstract

Objectives

We have reported previously that the TP53 codon72 polymorphism (rs1042522) is associated with the incidence and invasiveness of bladder cancer in a Han Chinese population. Using an enlarged sample, we investigated the role of rs1042522 and of tagSNPs that were predicted to be in linkage disequilibrium with codon72 in relation to the incidence, invasiveness, and prognosis of bladder cancer.

Methods and materials

A sample of 201 patients and 311 controls without cancer were genotyped for 5 tagSNPs using tetra-primer ARMS and/or an allele-specific PCR technique.

Results

The genotyped data were analyzed using Haploview 4.2, and a 10,000-permutation test showed that the rs9895829G allele (P = 0.003) and the rs1788227C allele (P = 0.027) were both associated with the incidence of bladder cancer. With respect to haplotype associations, after the data were adjusted for age, the haplotypes GTT (P = 0.001) and GGTC (P < 0.001) were correlated with a low incidence of bladder cancer. In contrast, none of the TP53 haplotypes were associated significantly with high tumor grade or muscle invasiveness. On the basis of Cox regression analysis, haplotype CGCC and invasiveness were associated with cancer-related death. Structural equation modeling showed that haplotypes GGCC and CGCC played opposing roles with respect to bladder cancer-related death; haplotype GGCC was a protective factor, whereas haplotype CGCC was a risk factor.

Conclusions

The TP53 codon72 polymorphism appears to play a crucial role in determining the association between TP53 haplotype and the incidence and prognosis of bladder cancer. Further functional assays to confirm whether these TP53 haplotypic variants interact with the proteins N-Myc and NDRG is necessary.

Keywords: Bladder cancer , TP53 haplotype , Prognosis , Invasiveness , Vulnerability