Cancer incidence and mortality among US young adults younger than 50 years.

e23093 Background: Early-onset cancers are increasingly recognized as a growing public health concern. We aimed to evaluate national trends in cancer incidence and mortality among individuals younger than 50 years in the US over more than two decades. Methods: We performed a population-based analysis using the United States Cancer Statistics database. Age-adjusted rates per 100,000 for cancer incidence (1999-2022) and mortality (1999-2023) among adults younger than 50 years were analyzed. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC). Analyses were stratified by sex, and leading cancer types were determined for males and females separately. Results: A total of 5,333,524 cancer cases and 884,750 deaths were recorded among individuals younger than 50. The most common cancers by incidence varied by sex. Among females, breast cancer was the most frequently diagnosed malignancy, followed by thyroid, colorectal, melanoma, and uterine cancers. Among males, colorectal cancer ranked first, followed by kidney, melanoma, leukemia, and non-Hodgkin lymphoma. Overall incidence per 100,000 increased from 99.5 in 1999 to 111 in 2022, with a significant increase from 1999-2008 (APC 1.10%), followed by stabilization from 2008-2022, resulting in an overall AAPC of 0.42% (95% CI 0.23 to 0.65). Females experienced a marked increase from 124.3 to 147.1 with an AAPC of 0.66% (95% CI 0.48 to 0.84), whereas male incidence showed a modest change from 74.3 to 75.2. In terms of mortality among females, breast cancer was the leading cause, followed by colorectal, cervical, lung, and brain/nervous system cancers. Among males, colorectal cancer led, followed by brain/nervous system tumors, lung, leukemia, and pancreatic cancer. Mortality declined substantially overall, dropping from 21.2 in 1999 to 14.2 in 2023 with an AAPC of −1.63% (95% CI −1.81 to −1.45). Cancer mortality rates saw comparable decreases for both sexes. For females, mortality fell from 21.8 to 15.4 (AAPC = −1.53%), although the rate of decline slowed after 2018. Male mortality decreased from 20.6 to 13.1 (AAPC −1.91%), stabilizing after 2019. Conclusions: Cancer incidence among US young adults has risen over the past two decades, driven predominantly by increases in females, while male incidence has remained stable, resulting in a widening gap between sexes. Despite rising incidence, mortality declined substantially in both sexes, although these improvements have recently plateaued. The disproportionate rise in female incidence likely reflects a combination of increased awareness, updates in screening guidelines, and a true increase in disease burden, potentially driven by cumulative hormonal and metabolic exposures. These findings warrant a closer examination of sex-specific risk factors driving mainly the increase in female-predominant cancer incidence and a reevaluation of current screening recommendations for adults under 50.