Rare appendix cancers are increasing among millennials and Gen X

A new study shows that appendix cancer is becoming more common among younger generations, mirroring a pattern that has been occurring with other cancers since the 1990s.

Cancer incidence rates among members of Generation X were two to three times higher than among people born in the 1940s, according to the study, which was published Monday in the Annals of Internal Medicine. Rates among older millennials, born in the 1980s, were more than four times higher.

Even with those increases, appendix cancer still remains extremely rare. Doctors diagnose an estimated 3,000 new cases in the United States each year, compared with more than 150,000 cases of colon and rectal cancers.

The findings come at a time of growing concern about the earlier onset of certain cancers, including colorectal, breast and kidney cancers. The new research describes what’s known as a “birth cohort” effect, or a disease becoming more common among successive generations. Such an effect lends credence to the idea that people born after a certain time have had similar exposures to something that is increasing their cancer risk more so than among people born decades before, said Dr. Andrea Cercek, a medical oncologist at Memorial Sloan Kettering Cancer Center who was not involved in the study.

And the fact that researchers have seen similar generational effects in colorectal and gastric cancers suggests there may be some shared risk factors between those cancers and appendix cancer, said Dr. Andrew T. Chan, a gastroenterologist at Massachusetts General Hospital who researches the epidemiology of colon cancer and also was not involved in the study.

Diet is one such possibility, he said. Our consumption of ultraprocessed foods has increased over time, and these foods — particularly processed meats and sugar-sweetened beverages — have been associated with increased risk for colon cancer.

Rates of metabolic disorders like obesity and diabetes — both of which have been associated with colon and stomach cancers — have been increasing over time. Young people, in particular, may be increasingly exposed to the negative effects of obesity and diabetes during a time of life when they are possibly more susceptible to developing cancer, Chan said.

Alcohol and changes to the gut microbiome are also thought to increase the risk of some gastrointestinal cancers.

Scientists still don’t know whether any of these environmental factors specifically influence appendix cancer, said Andreana Holowatyj, an assistant professor of hematology and oncology at Vanderbilt University Medical Center and lead author of the new study. Because the cancer is so rare, there is very little research on its causes.

She and other experts said that a multitude of factors are likely at play, including genetics. Better diagnosis may also be responsible for some of the documented increase, Holowatyj said. Until recently, some appendix cancers — which are often diagnosed incidentally when someone with appendicitis has their appendix removed — were misclassified as colon cancer.

But it’s unlikely that the increase in appendix cancer is merely a matter of improved classification, she said. The researchers found a particularly strong generational effect for a specific type of cancer that has always been classified as appendix cancer. Doctors treating appendicitis have also shifted away from surgery when possible, Cercek said, meaning that more cancer diagnoses after appendectomies wouldn’t be driving the result, either.

A research effort called the Appendiceal Cancer Consortium is working to pool data and specimens from across studies to better understand the risk factors and biological markers specific to appendix cancer.

While there is no good way to screen for the cancer right now, scientists hope that more knowledge about the disease will lead to greater awareness of the symptoms and, perhaps, earlier detection.

In other research, Holowatyj found that 77 per cent of patients diagnosed with appendix cancer presented with at least one sign or symptom of an abdominal condition, like pain or bloating. Often, those symptoms lasted for months, compared with the more acute symptoms that usually cause people with appendicitis to seek care.

“There’s an opportunity and a window for intervention there,” Holowatyj said.

For Richard Thoma, a marathon runner who was diagnosed with appendix cancer in 2023, the first signs of the condition were bloating and fatigue that blood tests couldn’t explain and which didn’t resolve with changes to his diet. Finally, a scan showed that Thoma had cancer in his appendix and abdominal cavity. He underwent a 12-hour surgery to remove the cancer as well as parts of his colon, stomach, spleen, gallbladder and rectum, followed by heated chemotherapy administered directly in his abdomen.

“They refer to it as the mother of all surgeries,” Thoma said.

He left the hospital with an IV to administer nutrients directly into his bloodstream and with an ostomy bag to collect waste. His weight dropped from 180 to 130 pounds. The cancer returned in 2024, and he underwent a second round of the surgery-and-chemotherapy procedure.

Today, he shows no evidence of appendix cancer, and he has a plan to raise awareness and money for research about the disease: He is running the New York City Marathon this fall.