How BMI Over Time Impacts GI Cancer Risk

Megan Brooks

May 16, 2023

Higher body mass index (BMI) and changes in BMI over time may increase a person's risk for gastrointestinal (GI) cancer, according to new data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

The researchers found that being overweight or obese in early and middle adulthood was associated with an increased risk for colorectal cancer (CRC) and noncolorectal GI cancers. Maintaining or increasing BMI over time among overweight or obese individuals was also associated with an increased GI cancer risk.

Aspirin use did not significantly modify these associations, suggesting that aspirin may not be as effective for cancer prevention among overweight or obese individuals.

The results provide "relatively consistent messaging that overweight or obesity from early to later adulthood as well as BMI increases throughout adulthood were associated with increased risk of GI cancers, especially CRC," the authors of an editorial accompanying the study write.

These "important findings highlight the unmet need to identify the critical time window linking adiposity and GI cancer," say editorialists Mengyao Shi, MBBS, MPD, and Yin Cao, ScD, MPH, of Washington University School of Medicine, St. Louis, Missouri.

The analysis was published online May 10 in JAMA Network Open

A growing body of evidence has revealed a strong association between obesity and GI cancers, with chronic inflammation being a likely cause. As rates of overweight and obesity continue to grow, better understanding of the association between obesity and cancer has become increasingly important.

In the current analysis, Holli A. Loomans-Kropp, PhD, MPH, with The Ohio State University in Columbus, and Asad Umar, PhD, DVM, with the National Cancer Institute, Rockville, Maryland, explored associations between BMI in early adulthood (age 20), middle adulthood (age 50) and later adulthood (age 55 and over) and GI cancer risk in 135,161 adults from the PLCO Cancer Screening Trial.

BMI was determined using self-reported height and weight at each age timepoint. The median age at enrollment was 62 years, and 50% of participants were women. Overweight BMI was 25.0 to 29.9 kg/m² and obese BMI was ≥30 kg/m².

During as many as 21 years of follow-up, 2803 individuals developed CRC and 2285 developed non-CRC GI cancers (esophageal, liver, gastric, and pancreatic).

Overweight BMI in early, middle, and later adulthood was associated with an increased risk of CRC (hazard ratio [HR], 1.23 for early and middle years; HR, 1.21 for later years). Obese BMI in middle and later adulthood was also associated with increased risk of CRC (HR, 1.55 and 1.39, respectively). 

The authors observed similar associations between BMI in middle and later adulthood and overall GI and non-CRC GI risk.

"When modeled continuously, we observed 2% to 4% increased risk of both CRC and noncolorectal GI cancer with each 1-unit increase in BMI across all time points," the researchers say.

Their data also suggest that BMI over time may be associated with GI cancer risk. Adults who exhibited no change in overweight or obese BMIs between early and later adulthood and those who exhibited increases in BMI from underweight or normal in early adulthood to overweight or obese BMI in later adulthood had a significantly higher risk for CRC and noncolorectal GI cancer.

Among frequent aspirin users, those with overweight or obese BMIs in early, middle, and later adulthood still had an increased risk for CRC and noncolorectal GI cancer (hazard ratios 1.44, 1.45, and 1.43, respectively).

The finding that regular weekly aspirin use did not modify GI cancer risk suggests that obesity may alter the cancer-preventive effect of aspirin, the researchers suggested. Individuals with obesity may need to increase aspirin frequency or dosage to see an effect, but upping the dose comes with its own risks, including GI bleeding.

Overall, until now, most epidemiologic studies have examined BMI at one timepoint, "missing the opportunity to delineate the contribution of adiposity throughout the life course," editorialists Shi and Cao explain.

"As we continue to investigate precision-based interventions to intercept the link between obesity and cancer, it is imperative to reiterate the importance of maintaining a healthy weight and lifestyle from an early age and incorporate it widely into cancer prevention strategies at all levels with immediate implementation," the editorialists conclude.

This study was supported in part by funds from The Ohio State University and the National Institutes of Health. The study authors report no relevant financial relationships. Cao has received personal fees from Geneoscopy for consulting.

JAMA Netw Open. Published online May 9, 2023. Full text, Editorial

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