Central obesity may account for most of the colorectal cancer risk linked to obesity: evidence from the UK Biobank prospective cohort

Abstract Background General obesity commonly represented by body mass index (BMI) is an established risk factor for colorectal cancer (CRC). However, it is unclear to what extent this association is accounted for by central obesity. We aimed to evaluate the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with CRC risk and to investigate if and to what extent these associations are independent from each other. Methods Data from more than 500,000 male and female participants aged 40–69, recruited in the UK Biobank study between 2006 and 2010, were analyzed. Multivariable Cox proportional hazards models were fitted and hazard ratios (HR) and their 95% confidence intervals (CI) were calculated. Results During a median follow-up of 12.5 years, of 460,784 participants, 5,977 developed CRC. Multivariable adjusted HRs (95% CIs) per standard deviation increase of BMI, WHR, and WC were 1.10 (1.07–1.13), 1.18 (1.14–1.22), and 1.14 (1.11–1.18), respectively. After mutual adjustment, the association with CRC was substantially attenuated for BMI (1.04 (1.01–1.07)), and remained substantially stronger for WHR (1.15 (1.11–1.20)). Furthermore, WHR showed strong, statistically significant associations with CRC risk within all BMI categories, whereas associations of BMI with CRC risk were weak and not statistically significant within WHR categories. BMI was also not associated with CRC risk in women and with rectal cancer after mutual adjustment. Conversely, WHR was strongly associated with CRC risk in both sexes and with both colon and rectal cancer risk before and after adjustment for BMI. BMI and WC could not be mutually adjusted for due to their high correlation. Conclusion Central obesity is a much stronger predictor of CRC and may account for most of the CRC risk linked to obesity. Our findings also emphasize the need for incorporating measures such as WHR alongside BMI in clinical practice to improve obesity prevention and management.