title: Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome.
abstract: OBJECTIVE
  Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations.
  
  
  METHODS
  In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence.
  
  
  RESULTS
  Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O.
  
  
  CONCLUSIONS
  The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.
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, Chang Gung Memorial Hospital, 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: Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Colorectal Section, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Jeng-Fu
authors.initials: JF
authors.lastname: You
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: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D003710:Demography; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013624:Taiwan
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein