Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome).
BACKGROUND
The marked variability in age at onset of colorectal cancer (CRC) in patients with hereditary nonpolyposis colorectal cancer (HNPCC) makes management decisions difficult. Environmental factors governing the phenotypic variability of cancer-associated syndromes such as HNPCC have not been elucidated.


METHODS
We determined whether tobacco use would alter CRC risk in carriers of HNPCC-associated mutations, using a retrospective cohort study of germline mutation (hMLH1 or hMSH2) carriers from the Hereditary Cancer Institute at Creighton University, one of the oldest and largest registries of HNPCC patients. The main outcome measure was age at CRC onset, estimated by means of Cox proportional hazards modeling.


RESULTS
Tobacco use, hMLH1 mutation carriage (as opposed to hMSH2), and male sex were significantly associated with increased risk of CRC (hazard ratios, 1.43, 2.07, and 1.58, respectively). Alcohol use did not alter CRC risk.


CONCLUSIONS
Smoking cessation should be an integral part of HNPCC management. This study underscores the gene x environment interactions in cancer development.
Watson
Patrice
P
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Neb, USA. patrice@creighton.edu
Ashwathnarayan
Ramesh
R
Lynch
Henry T
HT
Roy
Hemant K
HK
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000209:etiology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1