Obesity Metrics May Better Reflect CRC Link Than BMI

In a cohort study involving nearly 500,000 participants, researchers found that the population attributable fraction (PAF) of colorectal cancer (CRC) linked to excess weight, as measured by body mass index (BMI), was significantly underestimated.¹ In contrast, central obesity metrics such as waist circumference (WC) and waist-to-hip ratio (WHR) provided more consistent and higher PAF estimates.

These findings highlight the critical need to address central obesity as part of broader efforts to combat the obesity epidemic and reduce the burden of CRC.

This population-based UK Biobank cohort study is published in JAMA Network Open.

“Given that BMI does not distinguish between fat mass and muscle mass, it is more vulnerable to reflecting muscle mass loss, which is a key feature of cancer cachexia,” wrote the researchers of the study. “By contrast, WC and WHR are much less affected by loss of muscle mass. Consequently, the associations between high WC and WHR and, hence, the estimated proportion of CRC cases attributable to central obesity might be less prone to bias due to prediagnostic weight loss.”

Recently, global experts have called for a newly proposed framework to overhaul the current obesity diagnosis framework, which includes measures beyond BMI to define when obesity is a disease.² The Commission recommends using additional measures like WC and direct body fat assessment to complement BMI and reduce diagnostic errors.

In the current analysis, the researchers aimed to examine the PAFs of CRC cases that may be associated with high WC and WHR and compare them with those attributable to high BMI.¹

The prospective cohort analysis gathered data from over 500,000 participants aged 40 to 69 years between March 2006 and July 2010, from across 22 centers from England, Scotland, and Wales. Anthropometric data, including weight, standing height, WC, and hip circumference, were collected during the baseline assessment. Body weight and height were measured using a body composition analyzer and a mechanical telescopic height measuring rod, respectively.

The study included 458,543 participants. Over a median (IQR) follow-up period of 11.8 (10.9-12.5) years, 5944 participants were diagnosed with CRC. The PAF of CRC attributable to high BMI was 9.9% (95% CI, 5.5%-14.4%), markedly lower than the PAFs for high WC (17.3%; 95% CI, 12.3%-22.1%) and WHR (17.6%; 95% CI, 12.9%-22.2%).

After excluding the initial 7 years of follow-up, PAF estimates converged across obesity measures, reaching 15.7% (95% CI, 8.9%-22.4%) for BMI, 16.9% (95% CI, 9.8%-23.8%) for WC, and 18.0% (95% CI, 11.5%-24.6%) for WHR.

The researchers noted some limitations to their results. First, they did not account for cumulative lifetime exposure to obesity measures, potentially leading to PAF underestimates. Second, anthropometric measures, including BMI, WC, and WHR were based on single-time assessments. Furthermore, the UK Biobank cohort's evidence of healthy volunteer bias suggests participants were more health conscious and less socioeconomically deprived than the general population, potentially underestimating the prevalence of excess weight and central obesity.

Despite these limitations, the researchers believe the study findings suggest that calculating the proportion of CRC cases attributable to central obesity provided more accurate estimates of the PAFs of obesity-related CRC cases compared with BMI.

“We recommend incorporating central obesity measures, such as WC and WHR, alongside BMI, which does not account for fat mass distribution, in estimating the burden of CRC due to excess weight and the potential for prevention,” wrote the researchers.

References

1. Safizadeh F, Mandic M, Hoffmeister M, et al. Colorectal cancer and central obesity. JAMA Netw Open. 2025;8(1):e2454753. doi:10.1001/jamanetworkopen.2024.54753

2. Klein H. Global experts call for overhaul in obesity diagnosis framework. AJMC^®. January 14, 2025. Accessed January 21, 2025. https://www.ajmc.com/view/global-experts-call-for-overhaul-in-obesity-diagnosis-framework