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

• Published in: International journal of epidemiology Vol. 41; no. 4; pp. 1060 - 1072
• Main Authors: HUGHES, Laura Ae, WILLIAMSON, Elizabeth J, DEN BRANDT, Piet A.van, GOLDBOHM, R. Alexandra, WEIJENBERG, Matty P, ENGLISH, Dallas R, ENGELAND, Manon Van, JENKINS, Mark A, GILES, Graham G, HOPPER, John L, SOUTHEY, Melissa C, YOUNG, Joanne P, BUCHANAN, Daniel D, WALSH, Michael D
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2012
• Subjects: Adult; Aged; Anthropometry; Australia - epidemiology; Biological and medical sciences; Body Size - genetics; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Microsatellite Instability; Middle Aged; Miscellaneous; Netherlands - epidemiology; Proportional Hazards Models; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; Registries; Risk; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surveys and Questionnaires; Tumors; Australia; Netherlands; microsatellite instability; Rectal disease; Colorectal cancer; Risk; Corporal biometry; BRAF; Malignant tumor; Colorectal neoplasms; Metaanalysis; Colonic disease; Body mass index; Waist circumference; Microsatellite DNA; Cohort study; Body size; Risk factor; Digestive diseases; Intestinal disease; Instability; Mutation; Public health; Cancer; height
• ISSN: 0300-5771; 1464-3685
• DOI: 10.1093/ije/dys055

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. 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). Generally, overweight increases the risk of CRC. Taller individuals have an increased risk of developing a tumour with a BRAF mutation or MSI.