Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability A pooled analysis
article
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/m2 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, Pheterogeneity = 0.03). Similar associations were observed with respect to height and MSI tumours (HR: 1.26, 95% CI: 1.13-1.40, Pheterogeneity = 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. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved. Chemicals / CAS BRAF protein, human, 2.7.11.1; Proto-Oncogene Proteins B-raf, 2.7.11.1
Topics
Body mass indexBRAFCohort studyColorectal neoplasmsHeightMicrosatellite instabilityWaist circumferencebody masscohort analysisgenetic markerhealth riskinstabilitymutationtumorBRAF genecancer riskcolorectal cancerconfidence intervalgenegene mutationgenetic associationhazard ratiomajor clinical studymicrosatellite instabilitywaist circumferenceAdultAgedAnthropometryAustraliaBody SizeColorectal NeoplasmsFemaleHumansKaplan-Meier EstimateMaleMicrosatellite InstabilityMiddle AgedNetherlandsProportional Hazards ModelsProspective StudiesProto-Oncogene Proteins B-rafQuestionnairesRegistriesRiskNetherlands
TNO Identifier
954359
ISSN
03005771
Source
International Journal of Epidemiology, 41(4), pp. 1060-1072.
Article nr.
dys055
Pages
1060-1072
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