Dominance of digestive tract cancers in the US: a comprehensive analysis of organ-specific cancer incidence (1999-2021)

INTRODUCTION Cancer incidence varies widely across organ systems. Among these, digestive tract malignancies represent a major component of the national cancer burden, reflecting lifestyle, environmental, and demographic patterns. Understanding the system-level distribution of cancers is essential for optimizing prevention, screening, and healthcare resource allocation. MATERIALS AND METHODS We analyzed data from the United States and Puerto Rico Cancer Statistics (1999–2021), extracted from the CDC WONDER Online Database. Tumors were classified according to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) and grouped based on SEER site recodes (March 2018 revision). Non-invasive tumors were excluded from total invasive cancer counts, as per CDC WONDER methodology. Breast cancers were analyzed separately by invasiveness and sex. Chi-square tests were used to compare cancer distributions across organ systems and to assess sex differences in breast cancer. RESULTS The most common cancer systems were digestive (6.5 million), respiratory (5.2 million), breast (5.2 million), and male genital (5.1 million). The chi-square test confirmed a significant deviation from equal distribution (p < 0.001). Within the breast category, females had 1,203,735 in situ and 5,210,157 invasive cases; males had 4,831 in situ and 43,859 invasive cases, demonstrating a significant sex-based proportional difference (χ² = 2486.4, p < 0.001). CONCLUSIONS Digestive tract cancers represent the predominant organ-specific malignancies in the US population, emphasizing the urgent need for improved dietary and lifestyle interventions. The secondary analysis of breast cancer underscores persistent sex-based disparities in early detection. Together, these findings highlight the complex interplay between organ-specific risk factors and public health strategies across the US.