Around 9 in 10 appendix cancers have no known cause, and the disease is rising fast in younger people. This post looks at the appendix cancer early life question: whether an unusual event at the very start of life, like Rh disease or a newborn transfusion, could be part of the story, and why no one has studied it yet.

Bear with me on this one. It started with my husband David. It wandered into medical research. It ended at a question I cannot find an answer to anywhere, and I want to put it in front of you, because you might be part of the answer.

It started with David

David was born in 1973 with Rh disease. His mother was Rh-negative. He was Rh-positive, which he inherited from his father. Those two do not mix. His mother’s immune system treated his blood as foreign and made antibodies against it. Those antibodies crossed into David before he was born and began destroying his red blood cells.

It was serious. He needed a newborn blood transfusion to survive his first days. It was an exchange transfusion, where doctors slowly swap out the baby’s blood and replace it with donor blood.

David was the fourth child. His three older sisters never went through this. That fits the pattern. Rh disease often gets worse with each pregnancy, so the later babies tend to be hit hardest. David drew the short straw.

For most of his life this was just a piece of family history. Then he was diagnosed with appendix cancer, and I started looking at it differently.

What I found in the research

A baby who survives severe Rh disease goes through something intense in the first days of life. An immune system in overdrive. Red blood cells being destroyed. Very high bilirubin. A whole blood exchange. All of it lands during the exact window when the immune system and the gut are still forming.

That window is where the appendix cancer early life question lives. Researchers now treat early life as a critical period for the kind of gastrointestinal cancers that are rising in younger people. This is not a fringe idea. There is a solid body of work showing that colorectal and other gut cancers are climbing in people born after about 1960, and that the trail leads back to early-life exposures, things like cesarean birth, birth weight, whether a baby was breastfed, and antibiotics in pregnancy or infancy. One clear, free-to-read summary is Early Life: An Important Window of Susceptibility for Colorectal Cancer, published in Gastroenterology in 2022.

David’s own history is a different story, and I want to be straight about it. No one has studied whether Rh disease, a newborn exchange transfusion, or donor blood received as an infant changes cancer risk decades later. The research simply does not exist. What we do know is that the transfused donor cells are replaced by the body within a few months, and there is no established link between a newborn transfusion and any adult cancer. So I am not standing on evidence here. I am standing on a gap.

Appendix Cancer Early Life: What Makes This Worth Asking

Appendix cancer is close to a blank slate. Around 9 in 10 cases have no known cause. The roughly 1 in 10 we can explain traces to inherited genetic risk. A 2022 study in JAMA Oncology found that about 11 percent of appendix cancer patients who were tested carried an inherited cancer-related gene variation. You can read it here: Inherited Cancer Susceptibility Gene Sequence Variations Among Patients With Appendix Cancer. That still leaves the large majority of appendix cancer early life cases unexplained.

At the same time, appendix cancer is rising sharply in younger people, in Gen X and Millennials, for reasons researchers themselves call unexplained.

When that little is known about what causes a cancer, and it is climbing in exactly the birth cohorts where early-life exposures are the leading suspect, then asking the appendix cancer early life question is not a stretch. It is a reasonable question.

Let me be clear about what I am and am not saying. I am not saying Rh disease causes appendix cancer. I do not know that, and neither does anyone else. The simpler, more honest question is this. Do people who went through an unusual early-life event get appendix cancer at different rates than everyone else, and has anyone ever looked? As far as I can tell, on that last part, no one has. That is the gap. And that is the kind of question that, if enough of us point at it, can get a researcher’s attention.

This is where you come in

I want to see whether anything clusters in our community. Rh disease is only one possible early-life event. There are others. If any of these sound like your start in life, I would like to hear it.

• Born premature, or at very high or very low birth weight
• Rh disease or hemolytic disease of the newborn, meaning an Rh-negative mother
• A newborn blood transfusion or exchange transfusion
• Severe newborn jaundice, or treatment with blue lights (phototherapy)
• Cesarean delivery
• A NICU stay, or a serious illness or surgery as a newborn
• Formula-fed instead of breastfed
• Antibiotics during pregnancy or in infancy
• A mother who smoked during pregnancy

If you do not know your birth history, that is completely normal. Most of us do not. And “none of these that I know of” is just as useful for me to hear as a yes. I am not trying to prove anything. I am trying to see whether there is a pattern worth chasing.

If you are willing to share, tell me your story, and your birth year if you know it. You can comment, message me, or add it to our patient registry below. This is exactly the kind of thing patient communities are good at and researchers cannot do alone. We notice things first. Let us see what we notice.

Amanda

Appendix Cancer Early Life: Common Questions

Does Rh disease cause appendix cancer?

No. There is no evidence that Rh disease, hemolytic disease of the newborn, or a newborn blood transfusion causes appendix cancer. No study has looked at whether these early events change cancer risk later in life. That gap is the question this post raises.

What causes appendix cancer?

For most people, the cause is unknown. Around 9 in 10 appendix cancers have no identified cause. About 11 percent of patients carry an inherited cancer-related gene variation, based on a 2022 study in JAMA Oncology.

Is appendix cancer rising in younger people?

Yes. Appendix cancer is climbing sharply in people born in Gen X and the Millennial generations, and researchers have not fully explained why. That rise in younger birth cohorts is part of what makes the appendix cancer early life question worth asking.

What early-life events might be worth asking about?

Premature birth, very high or very low birth weight, Rh disease, a newborn transfusion or exchange transfusion, severe jaundice treated with phototherapy, cesarean delivery, a NICU stay, formula feeding instead of breastfeeding, and antibiotics during pregnancy or infancy.

Read more from Appendicure

• Early Onset Appendix Cancer: What a New Adenocarcinoma Study Suggests
• Appendix Cancer Genetic Testing: Why Dr. Shen Suggested a Germline Test for David
• The Data That Could Help Doesn’t Exist Yet. We’re Building It.