Abstract 2308: Sustained adherence to the American Cancer Society guideline for diet and physical activity for cancer prevention and 8-year all cancer risk: an emulated target trial in the Cancer Prevention Study-II Nutrition Cohort

Background: The 2020 American Cancer Society (ACS) Guideline for Cancer Prevention recommends maintaining a healthy body weight, engaging in regular physical activity, following a healthy diet, and abstaining from alcohol. While evidence of the cancer preventive effects of individual guideline components is well-established, few studies have assessed the long-term impact of adhering to multiple recommendations jointly using an emulated target trial design. An emulated target trial design mimics a hypothetical pragmatic randomized trial to answer causal questions using observational data. Objectives: To examine 8-year cancer risk under sustained adherence (intervention) to the physical activity, diet, and alcohol components of the ACS Guideline, both jointly and individually, compared to the behavior reported in the cohort (no intervention), stratified by body mass index (BMI) categories. Methods: Data from cancer-free, nonsmoking participants aged 47-80 years at baseline (1999) in the Cancer Prevention Study-II Nutrition Cohort were analyzed, including 30,111 individuals with normal weight (BMI 18.5 - <25 kg/m2), 27,986 with overweight (BMI 25 - <30 kg/m2) and 11,631 with obesity (BMI ≥30 kg/m2). Using an emulated target trial design, we assessed the effect of sustained adherence to the ACS Guideline components on cancer risk. Sustained adherence over 8 years was defined as meeting recommendations for physical activity (≥15 MET-hrs/wk), diet (≥6 serv/d and ≥21 unique fruits and vegetables per month, ≥2 serv/d of whole grains, ≤0.5 serv/d of red/processed meat, 0 serv/wk of sugar-sweetened beverages, ≤25% of total energy from processed foods and refined grains), and alcohol abstinence (0 serv/wk). The g-formula estimated absolute 8-year all cancer risk, adjusting for factors related to adherence and loss to follow-up. Results: The estimated 8-year risk of all cancers under no intervention was 13.5% for those with normal weight, 15.7% for those with overweight, and 14.4% for those with obesity. Compared to no intervention, sustained adherence to the joint ACS Guideline showed a 1.3% (95% CI: -2.3, -0.1), 1.0% (95% CI: -2.5, 0.4), and 0.7% (95% CI: (-2.7, 1.6) lower cancer risk for those with normal weight, overweight, and obesity, respectively. Among individual components, alcohol abstinence had the most pronounced mean risk reduction, ranging from 0.7% (95% CI: -1.7, 0.2) for those with overweight to 1.1% (95% CI: -1.9, -0.3) and 1.1 (95% CI: -2.2, 0.1) for those with normal weight and obesity, respectively. Conclusions: Sustained adherence to the ACS Guideline modestly reduced cancer risk, particularly for individuals with normal weight. Alcohol abstinence was a key contributor to the observed risk reductions. Citation Format: Valeria Elahy, Marjorie L. McCullough, Yu-Han Chiu, Alpa V. Patel, Erika Rees-Punia, Clara Bodelon, Anita R. Peoples, Ying Wang. Sustained adherence to the American Cancer Society guideline for diet and physical activity for cancer prevention and 8-year all cancer risk: an emulated target trial in the Cancer Prevention Study-II Nutrition Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2308.