Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the United States

Incidence rates of appendiceal adenocarcinoma (AA) are increasing across all age groups in the United States. Birth cohort patterns of AA can provide new, etiologic clues into increasing rates but have not been examined. To estimate incidence rates of AA across birth cohorts in the United States. Retrospective cohort study. The National Institutes of Health and National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) Program of 8 population-based cancer registries. A total of 4858 persons aged 20 years or older when diagnosed with a pathologically confirmed primary AA (nonmucinous, mucinous, goblet cell, or signet ring cell carcinoma) from 1975 to 2019. Five-year age groups and time periods were used to create 21 overlapping birth cohorts (1891-1899 to 1991-1999). The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945 birth cohort (birth years 1941 to 1949) and reported as incidence rate ratios (IRRs) with 95% CIs. Incidence rates of AA more than tripled among the 1980 birth cohort (IRR, 3.41 [95% CI, 2.54 to 4.56]) and quadrupled among the 1985 birth cohort (IRR, 4.62 [CI, 3.12 to 6.82]) compared with the 1945 birth cohort. Age-specific incidence rates of AA increased across successive birth cohorts after 1945-although to varying degrees-for all tumor histologic types. The rarity of AA precluded investigations specific to signet ring cell carcinomas of the appendix and across population groups (for example, sex and race). There are strong yet distinct birth cohort effects for AAs across histologic subtypes that remain unexplained-particularly among persons born after 1945. Given these patterns, there is a timely need for etiologic research as well as increased AA awareness among providers and the public. Similar trends have been reported for other gastrointestinal cancers, suggestive of potential shared cause contributing to this increasing cancer burden across generations. Appendix Cancer Pseudomyxoma Peritonei Research Foundation, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute.