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

Hughes, Laura A. E., Williamson, Elizabeth J., van Engeland, Manon, Jenkins, Mark A., Giles, Graham G., Hopper, John L., Southey, Melissa C., Young, Joanne P., Buchanan, Daniel D., Walsh, Michael D., van den Brandt, Piet A., Goldbohm, R. Alexandra, Weijenberg, Matty P. and English, Dallas R. (2012) Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis. International Journal of Epidemiology, 41 4: 1060-1072.


Author Hughes, Laura A. E.
Williamson, Elizabeth J.
van Engeland, Manon
Jenkins, Mark A.
Giles, Graham G.
Hopper, John L.
Southey, Melissa C.
Young, Joanne P.
Buchanan, Daniel D.
Walsh, Michael D.
van den Brandt, Piet A.
Goldbohm, R. Alexandra
Weijenberg, Matty P.
English, Dallas R.
Title Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 0300-5771
1464-3685
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1093/ije/dys055
Volume 41
Issue 4
Start page 1060
End page 1072
Total pages 13
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted 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 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.
Keyword Colorectal neoplasms
Braf
Microsatellite Instability
Body Mass Index (BMI)
Waist Circumference
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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