Aim: 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). Conclusion: 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.
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