Recent data show that cancer of the appendix, while rare, has been dramatically increasing among younger generations, making it part of a troubling trend of gastrointestinal cancers appearing more frequently at ages earlier than typically expected.
An analysis of data from the US National Cancer Institute (NCI) published in the Annals of Internal Medicine, found a sharp rise in appendiceal adenocarcinoma cases in the country, especially among Gen X and millennials.
The researchers noted that examining nearly 5 000 cases of appendix cancer, the incidence among Gen X adults was more than triple that of a control group of adults born between 1941 and 1949. For millennials, the cancer rate was four times higher when compared with the control group, reports Everyday Health.
“These rates are concerning,” said lead study author Andreana Holowatyj, PhD, an assistant professor of haematology, oncology and cancer biology at Vanderbilt University Medical Centre in Tennessee.
“But I also think it’s important to emphasise the rarity of this disease overall and not spark any alarm.”
Part of a trend
The appendix’s function in the gastrointestinal tract is not entirely clear, but the organ is thought to store good bacteria that can help restore gut health after events like diarrhoea.
Annually, appendix cancer affects only about one or two people per million, according to the NCI, but cases have been steadily climbing.
One study found that overall incidence of malignant appendix tumours in the United States more than doubled from 2000 to 2016 – and the diagnosis increases were highest among younger age groups.
“This is not a pattern that's just limited to cancers of the appendix. We’re seeing this trend across multiple cancers in the gastrointestinal tract,” said Holowatyj, whose lab focuses on early-onset cancers (those diagnosed before 50). These early-onset GI cancers include colorectal, stomach, pancreatic and oesophageal.
Why the increase in younger cases?
The chance of developing cancer rises steadily with age, with the highest cancer rates in adults 60 and older, and because it has been considered more of an old person’s disease, the jump in gastrointestinal cancers among younger adults has been puzzling.
Research into why this is occurring has only recently begun, and so far researchers haven’t identified a clear reason for the trend.
Evidence suggests, however, that these cancers may share similar modifiable risk factors – like obesity, poor diet, alcohol consumption and smoking, said Ardaman Shergill, MD, an oncologist specialising in gastrointestinal cancers at UChicago Medicine, who was not involved in the study.
“I speculate that risk-reducing strategies in other cancers, like not smoking, stopping or at least limiting alcohol, and regular exercise, may have beneficial effects in appendix cancer as well,” said Shergill.
Holowatyj said genetics might also play a role, and her lab is working to better understand how various risk factors may contribute to the disease.
Treatment
Surgery is the most common treatment option for appendix cancer, along with chemotherapy and other treatments.
“Often these are long surgeries needing many hours to complete,” said Shergill, while prognosis for survival depends on the type of appendix cancer, the stage at diagnosis, and how far it has spread.
The five-year survival rate for low-grade appendix tumours is between 67% to 97%. For more advanced appendix cancers, or those that have spread to other parts of the body, survival rates can be much lower.
Study details
Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the US
Andreana Holowatyj, Mary Washington, Richard Goldberg, Caitlin Murphy.
Published in Annals of Internal Medicine on 10 June 2025
Abstract
Background
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.
Objective
To estimate incidence rates of AA across birth cohorts in the United States.
Design
Retrospective cohort study.
Setting
The National Institutes of Health and National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) Programme of 8 population-based cancer registries.
Patients
A total of 4858 persons aged 20 years or older when diagnosed with a pathologically confirmed primary AA (non-mucinous, mucinous, goblet cell, or signet ring cell carcinoma) from 1975 to 2019.
Measurements
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.
Results
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 tumour histologic types.
Limitation
The rarity of AA precluded investigations specific to signet ring cell carcinomas of the appendix and across population groups (for example, sex and race).
Conclusion
There are strong yet distinct birth cohort effects for AAs across histologic subtypes that remain unexplained, particularly among people 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.
Everyday Health article – Appendix Cancer Sharply Rises Among Gen Xers, Millennials (Open access)
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