title: Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis.
abstract: BACKGROUND
  How body size influences risk of molecular subtypes of colorectal cancer (CRC) is unclear. We investigated whether measures of anthropometry differentially influence risk of tumours according to BRAF c.1799T>A p.V600E mutation (BRAF) and microsatellite instability (MSI) status.
  
  
  METHODS
  Data from The Netherlands Cohort Study (n = 120,852) and Melbourne Collaborative Cohort Study (n = 40,514) were pooled and included 734 and 717 colorectal cancer cases from each study, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), waist measurement and height were calculated and compared for subtypes defined by BRAF mutation and MSI status, measured from archival tissue.
  
  
  RESULTS
  Results were consistent between studies. When pooled, BMI modelled in 5 kg/m(2) increments was positively associated with BRAF wild-type (HR: 1.16, 95% CI: 1.08-1.26) and MS-stable tumours (HR: 1.15, 95% CI: 1.06-1.24). Waist measurement was also associated with BRAF wild-type (highest vs lowest quartile, HR: 1.59, 95% CI: 1.33-1.90) and MS-stable tumours (highest vs lowest quartile HR: 1.68, 95% CI: 1.31-2.15). The HRs for BRAF mutation tumours and MSI tumours were smaller and non-significant, but differences between the HRs by tumour subtypes were not significant. Height, modelled per 5-cm increase, was positively associated with BRAF wild-type and BRAF mutation tumours, but the HR was greater for tumours with a BRAF mutation than BRAF wild-type (HR: 1.23, 95% CI: 1.11-1.37, P(heterogeneity) = 0.03). Similar associations were observed with respect to height and MSI tumours (HR: 1.26, 95% CI: 1.13-1.40, P(heterogeneity) = 0.02).
  
  
  CONCLUSIONS
  Generally, overweight increases the risk of CRC. Taller individuals have an increased risk of developing a tumour with a BRAF mutation or MSI.
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Laura A E
authors.initials: LA
authors.lastname: Hughes
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Williamson
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: R
authors.initials: R
authors.lastname: Alexandra Goldbohm
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry; D001315:Australia / Q000453:epidemiology; D049628:Body Size / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012042:Registries; D012306:Risk; D011795:Surveys and Questionnaires
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf