Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis.
Hughes, Laura AE;
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;
+4 more...van den Brandt, Piet A;
Alexandra Goldbohm, R;
Weijenberg, Matty P;
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).
pp. 1060-1072.
ISSN 0300-5771
DOI: https://doi.org/10.1093/ije/dys055
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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.