Colorectal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 28, 2006; 12(28): 4485-4491
Published online Jul 28, 2006. doi: 10.3748/wjg.v12.i28.4485
Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking
Rhonda M Brand, David D Jones, Henry T Lynch, Randall E Brand, Patrice Watson, Ramesh Ashwathnayaran, Hemant K Roy
Rhonda M Brand, Randall E Brand, Hemant K Roy, Department of Internal Medicine, Evanston Northwestern Healthcare and Feinberg School of Medicine at Northwestern University, Evanston IL, Uinted States
David D Jones, Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln NE, Uinted States
Henry T Lynch, Patrice Watson, Ramesh Ashwathnayaran, Hereditary Cancer Institute, Creighton University, Uinted States
Supported by a grant from the American College of Gastro-enterology
Correspondence to: Dr. Rhonda M Brand, Division of Emergency Medicine and Department of Internal Medicine, Evanston Northwestern Healthcare and Feinberg School of Medicine at Northwestern University, SB 521 Walgreen’s Building, 2650 Ridge Ave, Evanston, IL 60201, Uinted States. rhbrand@enh.org
Telephone: +1-847-5704074 Fax: +1-847-7335451
Received: March 2, 2006
Revised: March 12, 2006
Accepted: March 20, 2006
Published online: July 28, 2006
Abstract

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.

Keywords: Hereditary non-polyposis colorectal cancer; Lynch syndrome; Smoking; Colorectal cancer; Fuzzy modeling; Risk assessment