title: Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking.
abstract: OBJECTIVE
  To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer (HNPCC) patients.
  
  
  METHODS
  Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC.
  
  
  RESULTS
  Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P < 0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P < 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P < 0.05), hMLH1 smokers (P < 0.1) and hMSH2 smokers (P < 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P < 0.05). Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P < 0.05).
  
  
  CONCLUSIONS
  CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.
authors.affiliation: Division of Emergency Medicine, Department of Internal Medicine, Evanston Northwestern Healthcare and Feinberg School of Medicine at Northwestern University, Evanston, IL 60201, USA. rhbrand@enh.org
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Brand
authors.forename: David D
authors.initials: DD
authors.lastname: Jones
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.forename: Patrice
authors.initials: P
authors.lastname: Watson
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ashwathnayaran
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000209:etiology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D017143:Fuzzy Logic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein