Birth cohort effects observed for increased appendiceal adenocarcinoma incidence

1. In this retrospective cohort study, age-specific incidence rates of appendiceal adenocarcinoma increased by time period.

2. Local drift for appendiceal adenocarcinoma was significantly different from net drift, which was suggestive of a birth cohort effect.

Evidence Rating Level: 2 (Good)

Study Rundown: Malignant tumors of the appendix are rare and are often discovered incidentally following surgery, during the histologic evaluation of colonic specimens. However, the incidence of appendiceal adenocarcinoma in the United States has been increasing over the last several decades in the context of a decreasing rate of appendectomies over the same time period. Birth cohort effects have been described for increased rates of malignancy, including colorectal and gastric cancers, and a recent population-based study demonstrated that Generation X is exhibiting larger increases in cancer incidence than any other generation since the Greatest Generation. The etiology behind the increasing burden of appendiceal adenocarcinoma remains uncertain but may be explained by birth cohort effects and generational changes in exposure. Hence, this retrospective cohort study used population-based data to investigate the incidence rates of appendiceal adenocarcinoma across birth cohorts in the United States. Overall, it demonstrated that age-specific incidence rates of appendiceal adenocarcinoma increased by birth cohort and time period. It also showed that local drift, a model-based estimate of annual percentage change in incidence rates specific to each age group, of appendiceal adenocarcinoma was significantly different from net drift, suggestive of a birth cohort effect. This study was limited by the rarity of appendiceal adenocarcinomas, which precluded the investigation of birth cohort effects across various population groups and for ultrarare signet ring cell carcinomas, as well as potential underreporting of mucinous appendiceal adenocarcinoma cases from vague historical classification systems. Overall, these results suggested that there may be an increasing burden of appendiceal adenocarcinoma across generations.

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Relevant Reading: Continued increasing incidence of malignant appendiceal tumors in Canada and the United States: A population-based study

In-Depth [retrospective cohort]: This retrospective cohort study used population-based data to evaluate the incidence of appendiceal adenocarcinomas across birth cohorts in the United States. Individuals diagnosed with appendiceal adenocarcinomas at 20 years of age or older between 1975 to 2019 were identified using data from the National Cancer Institute’s population-based cancer registries. The participants were classified as having mucinous or non-mucinous adenocarcinoma, goblet cell adenocarcinoma, or signet ring cell carcinoma. Incidence rate ratios (IRRs) were reported by time period using the ratio of age-specific incidence rates in each time period relative to the reference period of 1995 to 1999. IRRs were report by birth cohort using the ratio of age-specific incidence rates in each birth cohort relative to the reference cohort of 1945. Out of a total of 4,858 cases of appendiceal adenocarcinoma, 1,840 were mucinous, 1,428 were non-mucinous, 1,273 were goblet cell, and 317 were signet ring cell. Age-specific incidence rates increased by time period, including an IRR of 1.91 from the 1995 to 1999 period to the 2015 to 2019 period (95% confidence interval [CI], 1.69 to 2.16). In addition, age-specific incidence rates increased by birth cohort. Compared to the 1945 reference cohort, the IRR of the 1980 cohort was 3.41 (95% CI, 2.54 to 4.56) and that of the 1985 cohort was 4.62 (95% CI, 3.12 to 6.82). The age-specific incidence rates increased for all tumor histologic subtypes across successive birth cohorts to varying degrees. Net drift, or the annual percentage change in age-adjusted incidence rates, was 3.71% (95% CI, 3.35% to 4.07%), while local drift ranged from 2.38% to 4.70% and significantly differed from net drift. In summary, this study demonstrated birth cohort effects for appendiceal adenocarcinoma among individuals born after 1945.

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