title: Significant Association of Cyclo-oxygenase 2 Genotypes with Upper Tract Urothelial Cancer.
abstract: OBJECTIVE
  Reliable biomarkers are in urgent need for diagnosis, outcome prediction and treatment-effect monitoring for upper tract urothelial carcinomas (UTUC). Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor cells in more than half of the patients with UTUC investigated, the genomic contribution of COX2 to UTUC has not been studied. The study aimed to evaluate the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese population.
  
  
  METHODS
  A total of 218 patients with UTUC and 580 healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G-765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their association with UTUC risk.
  
  
  RESULTS
  The distribution of genotypes of COX2 G-765C and intron 5 were significantly different between patient and control groups (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The haplotype analysis showed that compared to the GG/TT haplotype of COX2 G-765C/intron 5, those carrying GG/AT variants have a significantly increased risk of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence interval=0.14-0.49).
  
  
  CONCLUSIONS
  Our results suggest that individual and combined COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and UTUC development.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Department of Urology, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Cheng-Hsi
authors.initials: CH
authors.lastname: Liao
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chin-Mu
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Hsin-Yuan
authors.initials: HY
authors.lastname: Fang
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Kao
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Department of Urology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Hsi-Chin
authors.initials: HC
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
authors.forename: Pei-Shin
authors.initials: PS
authors.lastname: Hu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Tzu-Chia
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Syu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Hao-Ai
authors.initials: HA
authors.lastname: Shui
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. artbau1@yahoo.com.tw artbau2@gmail.com.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: COX2; Taiwan; genotype; polymorphism; upper tract urothelial cancer