Abstract Background: In 2018, the World Cancer Research Fund (WCRF)/American Institute for Cancer Research published the Third Expert Report (TER) synthesizing the evidence on diet, adiposity, physical activity and risk of 19 cancers and 10 updated evidence-based cancer prevention recommendations. As part WCRF International’s Global Cancer Update Programme, we aimed to develop a prioritization support tool to identify what systematic literature reviews (SLR) of the epidemiological evidence published after the TER would help strengthen the TER’s conclusions and deepen our understanding on emerging topics. Methods: We developed a literature scanning and prioritization strategy in six actions. From January 2019 (after TER publication) to February 2024, we searched PubMed for: 1) meta- and pooled analyses, 2) randomized controlled trials (RCTs) and protocols, 3) Mendelian randomization (MR) studies, and 4) prospective cohort studies (≥100, 000 participants) on diet, adiposity, physical activity, sedentary behavior and cancer risk. In action 5, we utilized the fail-safe number and conditional power statistics to estimate the number of additional studies needed to change the existing TER meta-analytic findings. Finally, action 6 integrated data from actions 1-5, to construct an exposure-based prioritization ranking across all cancer sites. A prioritization score (PS) was derived by assessing the number of new studies, the concordance of association measures (direction and statistical significance) against the TER, and the volume of new associations not covered in the TER. Results: We reviewed 366 meta-analyses, 121 pooled analyses, 19 RCTs, 368 MR studies and 359 cohort studies covering 151 exposures and 28 cancers, comparing them to 1371 TER meta-analyses. TER meta-analyses most likely to change from not statistically significant to significant when adding new studies included folate and colorectal cancer, waist circumference and lung cancer in never smokers, poultry and breast cancer, total fat and ovarian cancer, tea and ovarian cancer, and red meat and kidney cancer, but most associations observed in the TER are unlikely to change with additional similar research. The median PS score across exposures was 6 (range -11 to 163). Top ranked exposures with new literature evidence included anthropometric measurements (PSheight 40 to PSBMI 163), physical activity (PS 100), sedentary behavior (PS 64), alcohol (PS 52), tea (PS 36), milk and dairy products (PS 29), micronutrients (PSretinol 27 to PSiron 38), vitamins (PSB12 22 to PSvitD 91), soy (PS 24), isoflavones (PS 23), and soft drinks (PS 22). Across exposures, the top cancers were colorectal, breast, lung, liver, and endometrium. Conclusions: The outputs from the prioritization support tool can help target SLRs that would most usefully contribute to evidence-based cancer prevention recommendations. Citation Format: Georgios Markozannes, Ahmad Jayedi, Sofia Cividini, Sayada Zartasha Kazmi, Margarita Cariolou, Rita Vieira, Sonia Kiss, Katia Balducci, Dagfinn Aune, Marc Gunter, Amanda Cross, Doris Chan, Konstantinos Tsilidis. A literature-based data scanning and prioritization study to guide future systematic literature reviews for WCRF International CUP Global Programme [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 6184.
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