• Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus.
• Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.

IMPORTANCE: In a population with significantly increasing rates of individuals with overweight or obesity, understanding the association of obesity with long-term disease risk, such as cancer, is necessary to improve public health.

OBJECTIVE: To investigate the association between body mass index (BMI) and gastrointestinal (GI) cancer risk (colorectal cancer [CRC] and noncolorectal GI cancer) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was a secondary analysis of data from the PLCO Cancer Screening Trial. Participants aged 55 to 74 years were enrolled and randomized to the intervention (screening group) or control group at 10 screening centers between November 8, 1993, and July 2, 2001. The initial analysis of PLCO Cancer Screening Trial data occurred after 13 years of follow-up or December 31, 2009, whichever came first. Participants were reconsented in 2011 and either continued follow-up or refused additional follow-up. For those who reconsented, follow-up for incident cancers continued until December 31, 2014, or death, whichever occurred first. Data analysis for this secondary analysis was performed from April 2022 through November 2022.

EXPOSURES: Body mass index and aspirin use, defined as the frequency of use of aspirin or aspirin-containing substances in the last 12 months.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the diagnoses of CRC and noncolorectal GI cancer. The association between BMI and cancer (CRC and noncolorectal GI cancer) was assessed using Cox proportional hazards regression modeling. The association between cancer risk and change in BMI was further analyzed at different ages, and an exploratory analysis was performed to evaluate GI cancer risk among aspirin users.

RESULTS: This analysis included 135 161 participants (median [range] age, 62 [55-78] years; 67 643 [50.0%] female). Overweight BMI in early adulthood (hazard ratio [HR], 1.23; 95% CI, 1.10-1.37) and overweight BMI in middle adulthood (HR, 1.23; 95% CI, 1.13-1.34) and later adulthood (HR, 1.21; 95% CI, 1.10-1.32) as well as obese BMI in middle adulthood (HR, 1.55; 95% CI, 1.38-1.75) and later adulthood (HR, 1.39; 95% CI, 1.25-1.54) were associated with increased risk of CRC. Similar results were observed for the association with overall GI and non-CRC GI risk and BMI in middle and later adulthood. Maintaining overweight or obese BMI or increasing BMI to overweight or obese in later adulthood was also associated with increased CRC risk. Aspirin use 3 or more times per week did not significantly modify this association.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the PLCO Cancer Screening Trial, overweight and obese BMI in early and middle adulthood was associated with an elevated risk of CRC and noncolorectal GI cancers. The results of the current study prompt further exploration into the mechanistic role of obese BMI in carcinogenesis.