Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis

Laura A. E. Hughes, Elizabeth J. Williamson, Manon van Engeland, Mark A. Jenkins, Graham G. Giles, John L. Hopper, Melissa C. Southey, Joanne P. Young, Daniel D. Buchanan, Michael D. Walsh, Piet A. van den Brandt, R. Alexandra Goldbohm, Matty P. Weijenberg*, Dallas R. English

*Corresponding author for this work

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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. 1799T4A 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.
Original languageEnglish
Pages (from-to)1060-1072
JournalInternational Journal of Epidemiology
Volume41
Issue number4
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Colorectal neoplasms
  • BRAF
  • microsatellite instability
  • body mass index
  • waist circumference
  • height
  • cohort study

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