In Asia, being heavier takes a toll on CRC incidence, mortality

02 Sep 2024 byJairia Dela Cruz
In Asia, being heavier takes a toll on CRC incidence, mortality

A strong, positive link between BMI and the risk of colorectal cancer (CRC) incidence and related deaths has been found in Asian populations.

Data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium (ACC) indicated that individuals exceeding the normal BMI range saw their risk of CRC incidence and mortality climb as high as 32 percent and 38 percent, respectively.

The risk rose steadily with BMI (p<0.001 for trend). For instance, the risk of CRC incidence increased by 9 percent in the >25.0–27.5 kg/m2 category (adjusted hazard ratio [aHR], 1.09, 95 percent confidence interval [CI], 1.03–1.16), by 19 percent in the >27.5–30.0 kg/m2 category (aHR, 1.19, 95 percent CI, 1.11–1.29), and by 32 percent in the >30.0 kg/m2 category (aHR, 1.32, 95 percent CI, 1.19–1.46) in comparison with the 23.0–25.0 kg/m2 category. [JAMA Netw Open 2024;7:e2429494]

The risk of CRC-related mortality followed a similar pattern, increasing by 18 percent in the >27.5–30.0 kg/m2 category (aHR, 1.18, 95 percent CI, 1.04–1.34) and by 38 percent in the >30.0 kg/m2 category (aHR, 1.38, 95 percent CI, 1.18–1.62) relative to the 23.0–25.0 kg/m2 category.

On further analysis, the association between BMI and CRC-related death was seen only among men with a BMI of >30.0 kg/m2 (aHR, 1.87, 95 percent CI, 1.49–2.34; p<0.001 for trend) but not among women (p=0.15 for trend; p=0.02 for heterogeneity). Additionally, the risk of both CRC incidence and mortality at increasing BMI categories was greater among individuals with colon cancer (8–38 percent; p<0.001 for trend) than among those with rectal cancer (7–18 percent; p<0.017 for trend).

These findings, which were presented in a paper published on JAMA Network Open, provide valuable insights into the burden of BMI on CRC incidence and deaths in Asian populations, according to the investigators.

Previous research has shown that obesity can promote tumour development through peroxidation pathways and dysregulated metabolism. Elevated insulin levels and a low-grade inflammatory state, both associated with obesity, likewise have the potential to stimulate tumour growth and progression. Moreover, obesity can foster neoplastic transformation by activating cellular growth pathways. [J Transl Med 2016;14:21;  Gut 2013;62:933-947; J Clin Oncol 2016;34:4270-4276]

“In the current study, we detected a positive association between BMI and CRC incidence among individuals who were both diabetic and nondiabetic. This finding may partly explain the association of BMI with CRC development, independent of an altered glucose metabolic pathway,” the investigators noted.

Given the unique characteristics of Asian populations, such as a tendency to develop diabetes at lower BMI levels, the investigators highlighted the importance of considering region-specific BMI cutoffs—consistent with those used in the ACC—to accurately assess the impact of obesity on CRC risk in Asia.

In terms of the sex differential association between higher BMI and CRC risk, “the differential distribution of adipose tissue may partly explain the higher risk to tumorigenesis and cancer mortality in men,” the investigators said. “Men have a predilection to develop central adiposity rather than generalized obesity, which is more common in women.”

Another explanation is the potential association between hormone replacement therapy (HRT) and BMI and the risk of CRC-related death in women, with a meta-analysis of five cohorts showing an inverse association between current use of HRT and CRC-specific mortality and overall mortality, they added. [BMC Cancer 2019;19:1199]

The study included a total of 709,214 individuals recruited from China, Japan, South Korea, Singapore, and Iran. Over a median follow-up of 15.2 years, 11,900 incident CRC cases were documented among 619,981 participants from 15 ACC participating cohorts (mean age 53.8 years, 52.0 percent female), and 4,550 CRC-related deaths were identified from all 17 ACC cohorts that included 650,195 participants (mean age 53.5 years, 51.9 percent female). The overall mean for BMI was 23.4 kg/m2, with 66.3 percent having a BMI between 18.5–25.0 kg/m2 and 25.4 percent being considered obese with a BMI between >25.0 and 30.0 kg/m2.