Introduction: Incidence of early-onset cancers (EOC, diagnosed at ages 20-49 years) is rising across cancer types in many regions worldwide but drivers remain largely unknown. We conducted a rapid review to indicate the current state of knowledge and key evidence gaps on potential risk factors for EOC.
Methods: Our systematic literature search of Medline and Embase identified articles referencing EOC published between 01/01/2015 and 18/09/2025. To enable rapid review, for colorectal cancer we included meta-analyses only from 2015 and for other cancers we included meta-analyses from 2015 and original studies reporting cancer-specific risk factors from 2021. We excluded studies with major methodological issues. We then mapped findings against risk factor classifications as defined by the International Agency for Research on Cancer (IARC) or the World Cancer Research Fund (WCRF).
Results: In total, 46 studies were included (10 meta‑analyses, 36 original studies), nine (20%) with minor methodological issues. Most studies focused on common cancers, particularly breast and colorectal cancer (25/46), with limited data for less common cancers. The defined EOC age-range varied by study and cancer type. EOCs were associated with several modifiable risk factors as classified by IARC or WCRF (particularly alcohol, tobacco and obesity). An additional 13 identified risk factors predominantly fell into three domains: clinical or medical history (e.g., inflammatory bowel disease, diabetes, metabolic syndrome, non-alcoholic fatty liver disease); biological and hormonal mechanisms (e.g., free testosterone, insulin‑like growth factor‑1); and genetics and genomics (family history of the same cancer type, pathogenic/likely pathogenic variants). Several risk factors were associated with statistically significant decreases in EOC risk for at least one cancer (e.g., older age at menarche, breastfeeding, ≥2 pregnancies, sex hormone-binding globulin, physical activity).
Conclusions: Findings highlight key evidence gaps, the importance of prevention strategies targeting known cancer risk factors, and further investigations of underlying physiological and genetic influences.