Study Reports Increasing Incidence Rates of Appendiceal Adenocarcinoma in Those Born After 1945

A recent study published in the Annals of Internal Medicine¹ estimated incidence rates of appendiceal adenocarcinoma across birth cohorts in the United States. Andreana N. Holowatyj, PhD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, and colleagues observed a sharp increase in incidence rates of appendiceal adenocarcinoma for those born after 1945, particularly for those born between 1964 and 1980 (Generation X) and notably for others born between 1981 and 1986 (Millennials). These patterns suggest a timely need for etiologic research and increased awareness of appendiceal adenocarcinoma among physicians and the public.

The study investigators focused on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program to estimate age-specific incidence rates of appendiceal adenocarcinoma per 100,000 persons in 5-year time periods between 1975 and 2019. The researchers created 21 overlapping birth cohorts and estimated the incidence rates relative to a 1945 birth cohort. The researchers identified a total of 4,858 persons aged 20 years or older who were diagnosed with a pathologically confirmed primary appendiceal adenocarcinoma (nonmucinous, mucinous, goblet cell, or signet ring cell carcinoma).

The age-specific appendiceal adenocarcinoma rates increased by time period, according to the study authors, and incidence rates of appendiceal adenocarcinoma more than tripled among the 1980 birth cohort. Among the 1985 birth cohort, incidence rates of appendiceal adenocarcinoma quadrupled. This pattern was reflected across all appendiceal adenocarcinoma histologic subtypes, although the magnitude varied. The increase in appendiceal adenocarcinoma incidence rates was especially large among Generation X and Millennial populations.

Incidence rates in younger generations are often indicative of future disease burden. Researchers noted that the findings suggest the need for histology-specific investigations of appendiceal adenocarcinoma as well as more awareness of rare appendiceal adenocarcinoma among physicians and the public. They shared these concluding comments: “There are strong yet distinct birth cohort effects for [appendiceal adenocarcinomas] across histologic subtypes that remain unexplained—particularly among persons born after 1945.… Similar trends have been reported for other gastrointestinal cancers, suggestive of potential shared cause contributing to this increasing cancer burden across generations.” 

DISCLOSURE: This work was, in part, supported by the Appendix Cancer Pseudomyxoma Peritonei Research Foundation as well as National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development grant K12 HD043483 and NIH/National Cancer Institute grant P50 CA236733. For full disclosure of all study authors, visit acpjournals.org.

REFERENCE

1. Holowatyj AN, Wasington MK, Goldbert RM, et al: Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the United States. Ann Intern Med. June 10, 2025 (early release online).

This study was supported by grants from the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development as well as the NIH/National Cancer Institute.