Appendiceal adenocarcinoma incidence has increased substantially in younger U.S. birth cohorts, particularly among those born after 1980, according to a population-based study.

From 1975 to 2019, the incidence of appendiceal adenocarcinoma (AA) increased across successive birth cohorts after 1945, with the steepest increases observed among persons born in the 1980s and 1990s. Compared with the 1945 birth cohort, incidence was more than 4 times higher in the 1985 cohort (incidence rate ratio [IRR], 4.62; 95% CI, 3.12–6.82) and more than three times higher in the 1980 cohort (IRR, 3.41; 95% CI, 2.54–4.56).

The findings are based on data from 4,858 adults aged 20 years or older diagnosed with pathologically confirmed AA between 1975 and 2019, using 8 U.S. registries from the Surveillance, Epidemiology, and End Results (SEER) Program. Tumors were categorized by histologic subtype: mucinous, nonmucinous, goblet cell, and signet ring cell adenocarcinomas.

Incidence increased across all AA subtypes in more recent cohorts. For example:

• Goblet cell adenocarcinoma incidence was nearly 10 times higher in the 1985 cohort than in the 1945 cohort (IRR, 9.57; 95% CI, 4.90–18.67).

• Mucinous adenocarcinoma: IRR, 2.10 (95% CI, 1.01–4.37).

• Nonmucinous adenocarcinoma: IRR, 2.75 (95% CI, 1.27–5.97).

The age-adjusted incidence of AA increased by 3.71% annually during the study period (net drift, 95% CI, 3.35%–4.07%). Comparing the time period 1995–1999 (reference) with 2015–2019, the overall AA incidence nearly doubled (IRR, 1.91; 95% CI, 1.69–2.16).

To isolate generational effects, the researchers applied an age–period–cohort model. The analysis demonstrated a strong birth cohort effect, indicating a higher lifetime risk of AA among those born more recently, independent of age or calendar year of diagnosis.

Detection bias was considered unlikely to explain these trends. Colonoscopy has low sensitivity for detecting appendiceal tumors, and imaging often does not visualize the appendix when symptoms are nonspecific.

Due to limited case counts, the study did not stratify incidence by sex or race. Signet ring cell carcinoma was excluded from birth cohort comparisons for the same reason.

Although the study did not investigate causality, the authors noted that the increasing AA incidence mirrors similar trends in other gastrointestinal cancers, including colorectal and gastric cancers. Shared risk factors may include environmental exposures, dietary habits, obesity, and other lifestyle factors that differ across generations.

As millennials continue to enter midlife, the findings suggest a potential increase in AA-related disease burden. The authors noted the need for further etiologic research, as well as improved awareness and early detection strategies.

Author disclosures are available in the published study below.

Source: Annals of Internal Medicine