Chia-Cheng Yu1,2,3, Lih-Chyang Chen4, Wen-Hsin Lin5, Victor C Lin6,7, Chao-Yuan Huang8, Te-Ling Lu5, Cheng-Hsueh Lee9,10, Shu-Pin Huang11,10,12,13, Bo-Ying Bao14,15,16. 1. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 2. Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. 3. Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan, R.O.C. 4. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, R.O.C. 5. Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. 6. Department of Urology, E-Da Hospital, Kaohsiung, Taiwan, R.O.C. 7. School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan, R.O.C. 8. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C. 9. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. 10. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 11. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. shpihu@yahoo.com.tw bao@mail.cmu.edu.tw. 12. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 13. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, R.O.C. 14. Department of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. shpihu@yahoo.com.tw bao@mail.cmu.edu.tw. 15. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. 16. Department of Nursing, Asia University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer. PATIENTS AND METHODS: A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients. RESULTS: A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer. CONCLUSION: YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression. Copyright
BACKGROUND/AIM: This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer. PATIENTS AND METHODS: A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients. RESULTS: A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer. CONCLUSION:YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression. Copyright