title: TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study.
abstract: OBJECTIVE
  TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk.
  
  
  METHODS
  We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development.
  
  
  RESULTS
  The carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14-0.86; CC genotype: HR = 0.28, 95% CI = 0.13-0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15-0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08-0.46 and HR = 0.25, 95% CI = 0.09-0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09-0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11-0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors.
  
  
  CONCLUSIONS
  The study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Abram Bunya
authors.initials: AB
authors.lastname: Kamiza
authors.affiliation: Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.affiliation: Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|School of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Huei-Tzu
authors.initials: HT
authors.lastname: Chien
authors.affiliation: Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Chiu
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Tsai-Ping
authors.initials: TP
authors.lastname: Lo
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Kuan-Yi
authors.initials: KY
authors.lastname: Hung
authors.affiliation: Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|School of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jeng-Fu
authors.initials: JF
authors.lastname: You
authors.affiliation: Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.|Department of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C501486:MLH1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein