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Association Analysis of Wnt Pathway Genes on Prostate-Specific Antigen Recurrence After Radical Prostatectomy

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although aberrant Wnt/β-catenin (CTNNB1) signaling has been observed in numerous types of human cancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa.

Methods

We comprehensively studied the contribution of genetic variations in CTNNB1 and adenomatous polyposis coli (APC), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case–control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire APC and CTNNB1 genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls.

Results

Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the APC tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan–Meier analysis and Cox regression model. Interestingly, we found that the APC rs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test, P = 0.037) compared with the GG genotype.

Conclusions

This is the first report documenting the potential prognostic role of the APC rs3846716 GA/AA genotype on PSA recurrence after RP.

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Acknowledgment

We would like to thank National Genotyping Center of National Research Program for Genomic Medicine, National Science Council (NSC), Taiwan, for their technical support. This work was supported by NSC Grant NSC-96-2321-B-039-005-MY2, NSC-96-2314-B-037-012-MY3, and China Medical University grant CMU97-183.

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Authors and Affiliations

  1. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD & Chia-Chu Liu MD

  2. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD

  3. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD

  4. Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan

    Wen-Chien Ting MD

  5. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan

    Lu-Min Chen MD & Li-Chia Huang MD

  6. Clinical Research and Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Chien-Wei Chen PhD

  7. Department of Health Care Administration, Oriental Institute of Technology, Taipei, Taiwan

    Chi-Jeng Hsieh MS

  8. Graduate Institute of Health Care Organization Administration, College of Public Health, National Taiwan University, Taipei, Taiwan

    Chi-Jeng Hsieh MS

  9. Department of Health Services Administration, China Medical University, Taichung, Taiwan

    Wen-Hui Yang PhD

  10. Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan

    Ta-Yuan Chang PhD

  11. Department of Pharmacy, China Medical University, Taichung, Taiwan

    Hong-Zin Lee PhD & Bo-Ying Bao PhD

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  1. Shu-Pin Huang MD, PhD
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  2. Wen-Chien Ting MD
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  3. Lu-Min Chen MD
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  4. Li-Chia Huang MD
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  6. Chien-Wei Chen PhD
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  8. Wen-Hui Yang PhD
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Corresponding author

Correspondence to Bo-Ying Bao PhD.

Additional information

S.-P. Huang and B.-Y. Bao contributed equally to this work.

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Huang, SP., Ting, WC., Chen, LM. et al. Association Analysis of Wnt Pathway Genes on Prostate-Specific Antigen Recurrence After Radical Prostatectomy. Ann Surg Oncol 17, 312–322 (2010). https://doi.org/10.1245/s10434-009-0698-8

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  • DOI: https://doi.org/10.1245/s10434-009-0698-8

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