A CDH1 gene mutation runs in my family. We discovered it because my mom was diagnosed with stomach cancer. Subsequent genetic testing confirmed she inherited from her father a CDH1 gene mutation that is associated with stomach cancer. Ultimately, she died of the disease. However, her sacrifice saved at least five people, and probably more, from developing stomach cancer.
Here’s our CDH1 gene mutation story.
In 2015, doctors diagnosed my mom with gastric cancer. Before the diagnosis, my mom had been suffering from bad acid reflux, loss of appetite, pain after eating, and feeling full after only a few bites. Sure-tell signs of diffuse gastric cancer. However, they are also signs of other, more common illnesses for an otherwise healthy person. After months of testing, doctors still could not figure out what was causing my mom’s symptoms. Eventually, the doctors decided to remove her gallbladder. During surgery, the surgeon noticed cancer on her gallbladder. After several days, they determined it had originated from her stomach.
Needless to say, the diagnosis devastated our family. Her cancer was not a solid tumor. Rather, it was diffuse. It had spread beyond her stomach to her gallbladder and throughout her peritoneum. The disease was in stage 4. Unbeknownst to anyone before her diagnoses, my mom inherited a CDH1 mutation from her father. Despite having the mutation, he died in his late 80s of causes unrelated to CDH1 gene mutations.
Gastric cancer is the third-leading cause of cancer deaths worldwide and the fifth-leading type of cancer. As my mom’s case demonstrates, this particular kind of gastric cancer is very difficult to detect at an early stage, tricky when trying to diagnose, and usually comes with a grim prognosis. Although doctors predicted my mom had only months to live post-diagnosis, she lived nearly three more years. She died in January 2018.
My mom’s illness flipped our world upside. However, in some ways it was a blessing in disguise. In typical fashion, my mom saved the lives of several family members. During her illness, my mom learned that some stomach cancers are caused by genetic mutations passed from parent to child. Because of her persistence in getting genetic testing, we learned that she carried one of the hereditary genetic mutations known to cause diffuse gastric cancer. The mutation — deletion of exon 3 in the CDH1 gene — is one of over 120 mutations known for that gene. The CDH1 gene provides the code for making epithelial cadherin protein (E-cadherin). Among other functions, E-cadherin helps cells stick to one another and serves as a tumor suppressor by preventing cells from uncontrolled growth and division.
CDH1 gene mutation carriers, like my mom, are born with one defective copy of that gene. If the good copy mutates, the mutation carrier loses proper E-cadherin function because CDH1 gene mutation results in non-functional E-cadherin protein. With non-functioning E-cadherin protein, a carrier no longer benefits from E-cadherin’s expected functions. Without its expected cell adhesion and tumor suppressing functions, the likelihood of gastric cancer developing and advancing increases significantly.
CDH1 mutation carriers are more likely than not to develop hereditary diffuse gastric cancer. Studies report the chance is 56-80%. Nobody knows how to predict which carriers will develop the disease and which carriers wont, nor does anyone know how to predict when a carrier will get the disease. Female carriers also have a 40-50% chance of developing lobular breast cancer.
Shortly after learning my mom is a CDH1 gene mutation carrier, we learned that the recommended course of action, if their disease state permits, is to have a total gastrectomy (remove the stomach). Unfortunately, my mom’s cancer was too advanced to make her a candidate for the surgery. Her only options were chemotherapy and immunotherapy. For those of us who were potentially carriers, though, we were all candidates for the surgery. Of the twelve of us adult descendants of my mom’s dad who could potentially be CDH1 gene mutation carriers, six of those twelve have the mutation.
Five of the six carriers (because not my mom) confronted whether to have their stomach removed. Doctors recommend total gastrectomy because the disease oftentimes goes undetected, in spite of using the best detection techniques, until it is too advanced to treat effectively. Depending on the situation, total gastrectomy can prevent a carrier from ever developing the disease, “cure” a carrier who has early signs of the disease, or help put a carrier with disease in remission. Although a total gastrectomy can save a life, it comes with a significant risk of life-changing consequences.
When I first learned about potentially needing to decide whether to have the surgery, my first reaction was that if I tested positive for the mutation, I would not have my stomach removed. I didn’t know anything about the procedure or stomachless lifestyle and was not completely informed on the disease, but to me it sounded too severe an action. My mom, moreover, was responding well to therapy, and we were all very optimistic.
Much of my family, however, was leaning toward having the surgery if a carrier. Because of how the disease develops, endoscopy and biopsy results reporting a normal stomach does not mean the mutation carrier does not have the disease. Having no effective way for confirming no disease, a carrier is left having to decide between: (a) not having the gastrectomy but taking the chance of getting the disease or (b) having the gastrectomy but taking the risks that come with gastrectomy. This is a tough decision for a healthy person. Someone having no symptoms to alleviate. Someone with a grandfather who carried the mutation and died in his late 80s with no signs of the disease, an aunt in her early 70s with no detectable disease, and an aunt in her early 60s who, before her gastrectomy, had no detectable disease (we learned after her gastrectomy that her stomach showed early signs of disease). But, I have a mother who died at 65 years old because of the disease.
In January 2018, nearly three years after being diagnosed, my mom died of stomach cancer. Over 750 people attended her funeral. She and my dad fought so hard. They traveled from Kansas City to Houston on a regular basis so that she could see oncologists at a world-renowned cancer hospital. They had excellent local care near their home. My mom was so optimistic despite knowing her grim odds.
Despite her misfortune, she remained herself around others. Always putting first the well-being of friends, family, and even strangers. She was selfless, brave, and inspiring. Something she did not talk much about, however, was how she must have been so scared and devastated. A big reason her spirits remained high is because of my amazing dad. He was with her every step of the way. He went above and beyond. His love and dedication to her is unquestionable.
Hopefully, her legacy can live on by getting the word out about CDH1 and other disease-causing genetic mutations. Even after life, my mom’s impact will continue to save lives and shape future generations.
In February 2018, one month after my mom died, I learned that I carry the CDH1 gene mutation. After getting my genetic testing results, I talked with several geneticists, surgeons, and other CDH1 experts. My family and I debated all potential options. We had my mom’s experience. We had family who had already had their stomach removed. We had read articles and consulted with others who had the mutation and surgery. We were very well informed.
It became a no-brainer. I needed to have my stomach removed. Without a stomach, I cannot get stomach cancer. Despite originally thinking that living without a stomach was crazy, my attitude changed after watching my mom’s ensuing nasty battle with the disease. Not only does cancer looks miserable, life after total gastrectomy did not look so bad, especially in comparison to stomach cancer.
On June 1, 2018, an amazing team of surgeons, nurses, and others at the University of Chicago removed my stomach. Before surgery, I had an upper endoscopy and biopsies as measures to help diagnose whether I had the disease. Both reported a normal stomach. After surgery, doctors examined my stomach for signs of disease. The pathology results showed early signs of disease. But it had not spread. Had I not had my stomach removed, the disease was likely to go unnoticed until too late. My mom, my dad, family, the surgical team, geneticists, GI docs and countless others saved my life.
So far, after more than a year without a stomach, life is amazing. Sure, the initial recovery was really difficult. Plus, I’m still learning the limits of and signals from my new digestive system, including what impacts the new system has on my body as a whole. However, I live a normal life. I eat normal except for smaller more frequent meals. I exercise, work, and travel like normal people. I have had no major complications. Also, now I have no risk of stomach cancer. Finally, perhaps one of the greatest side effects of all this is that I have a greater sense of purpose in life and a newfound appreciation for how special life, health, and a strong community really are.
Watch another CDH1 mutation carrier tell her story!