title: Genetic variation in the transforming growth factor-β-signaling pathway, lifestyle factors, and risk of colon or rectal cancer.
abstract: BACKGROUND
  The transforming growth factor-β-signaling pathway has been identified as being involved in colorectal cancer.
  
  
  OBJECTIVE
  The aim of this study was to determine how diet and lifestyle factors in combination with genetic variation in the transforming growth factor-β-signaling pathway alters colorectal cancer risk.
  
  
  METHODS
  We used data from 2 population-based case-control studies.
  
  
  METHODS
  Participants included patients with colon cancer (n = 1574) and controls (n = 1970) and patients with rectal cancer ( n = 791) and controls (n = 999).
  
  
  METHODS
  The primary outcomes measured were newly diagnosed cases of colon or rectal cancer.
  
  
  RESULTS
  Colon and rectal cancer risk increased with the number of at-risk genotypes within the transforming growth factor-β-signaling pathway (OR 3.68, 95% CI 2.74,4.94 for colon cancer; OR 3.89, 95% CI 2.66,5.69 for rectal cancer). A high at-risk lifestyle score also resulted in significant increased risk with number of at-risk lifestyle factors (OR 2.99, 95% CI 2.32,3.85 for colon cancer; OR 3.37, 95% CI 2.24,5.07 for rectal cancer). The combination of high-risk genotype and high-risk lifestyle results in the greatest increase in risk (OR 7.89, 95% CI 4.45,13.96 for colon cancer; OR 8.75, 95% CI 3.66,20.89 for rectal cancer).
  
  
  CONCLUSIONS
  The study results need validation in other large studies of colon and rectal cancer.
  
  
  CONCLUSIONS
  In summary, our data suggest that there is increased colon and rectal cancer risk with increasing number of at-risk genotypes and at-risk lifestyle factors. Although the integrity of the pathway can be diminished by a number of high-risk genotypes, this risk can be offset, in part, by maintaining a healthy lifestyle.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
mesh_terms: D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D014481:United States / Q000453:epidemiology
chemical_list: D004273:DNA, Neoplasm; D016211:Transforming Growth Factor alpha