Introduction: Currently, populations are identified for cancer screening interventions one cancer type at a time. With new developments in cancer screening, including multi-cancer early detection tests, it is important and timely to understand the overall cancer burden in populations outside those traditionally targeted for single-cancer screenings. Thus, we sought to identify the most important risk factors for developing any invasive cancer, and to calculate associated 5-year absolute risks, with a particular focus on persons under age 50 years.

Methods: Two large American Cancer Society cohorts followed prospectively for cancer, the Cancer Prevention Study-II Nutrition Cohort (CPS-IINC) enrolled from 1992-1993 and Cancer Prevention Study 3 (CPS-3) enrolled from 2006-2013, were used to examine a broad range of cancer risk factors. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations between potential risk factors and subsequent overall risk of any invasive cancer. The Individualized Coherent Absolute Risk Estimation tool used these HRs to estimate absolute risk in 5-year age groups.

Results: 15,226 cancers were identified among 429,991 participants within 5 years of follow-up. Several risk factors including smoking history, obesity, alcohol, family history of cancer, and various chronic medical conditions (e.g., diabetes, hypertension) were associated with a higher risk of cancer. Persons above age 50 years, regardless of other risk factors considered, had at least 2% absolute risk per 5 years. Among persons under age 50 years, smoking status was the most important factor differentiating risk. For men under age 50, absolute risk of any cancer did not exceed 2% except for men ages 45-49 years who currently smoke or recently quit (within 30 years). For women under age 50, absolute risk exceeded 2% starting at age 35-39 years for current or recent former smokers, and all women, even long-term nonsmokers, at age 45-49 had over 2% absolute risk.

Conclusions: Smoking history is important in differentiating absolute risk of any cancer in adults under age 50 years. More research to understand the extent to which other cancer risk factors influence risk for specific populations aged <50 years should be carried out.

Citation Format: Alpa V. Patel, Emily Deubler, Lauren R. Teras, Graham A. Colditz, Cari J. Lichtman, William G. Cance, Christina A. Clarke. Identifying populations at elevated risk of cancer outside those traditionally targeted for screening and prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2235.