By Kelly Fulk, Certified Genetic Counselor
As my first foray into blogging, I’m very excited to write the second “Mutation of the Month” about Hereditary Diffuse Gastric Cancer post for Georgia. I want to focus on hereditary cancer syndrome because it flies a little under the radar. Hereditary Diffuse Gastric Cancer (HDGC) is a syndrome associated with mutations in the CDH1 gene, and people with the syndrome are primarily at risk to develop specific types of stomach cancer and breast cancer. Before I dive into the details, a quick detour: if you need a refresher on the differences between “genes” and “mutations,” please see my colleague Sarah Witherington’s July 13, 2014 “Mutation of the Month” post. http://www.ihavelynchsyndrome.com/mutation-month-fap/#.U90-BvldWSo
Now, without further ado, let’s get back on track. Like Lynch syndrome and many other hereditary cancer syndromes, HDGC is inherited in an autosomal dominant manner. (And if you don’t remember, this means someone who carries a CDH1 mutation has a 50/50 random chance to pass it on to sons or daughters each time they have a child). This fact can make parents who carry these mutations feel guilty if they find out that one (or more) of their children inherited the mutation and the associated cancer risks. Of course, this makes no sense – from a scientific standpoint. There is nothing one can do naturally to control which genes they pass to their kids, but this is still a tough issue for many people with hereditary cancer syndromes. Genetic counselors and support groups are two of the many resources available to help individuals and families deal with challenging concerns that can naturally come along with a hereditary cancer syndrome diagnosis. Sometimes it just helps to know that there are outlets for the powerful feelings and emotions that can arise.
HDGC is associated with increased lifetime risks for diffuse gastric cancer and lobular breast cancer. Diffuse gastric cancer is a particularly aggressive type of stomach cancer that is difficult to detect with screening it causes the stomach lining to thicken, making it tricky to see during an endoscopy (a procedure like a colonoscopy that looks at the esophagus, stomach, and small bowel). Imagine trying to look with a tiny camera at the inside of the stomach and trying to determine if it is thicker than it should be, not very easy. People with CDH1 mutations have about an 80% lifetime chance to develop diffuse gastric cancer by age 80, but the average age of diagnosis is in the mid-30’s. Some people have been diagnosed as young as 14, so HDGC is a hereditary cancer syndrome where genetic testing may be considered for children. As Sarah mentioned in her earlier post on familial adenomatous polyposis, genetic testing for children is particularly complicated and sensitive, and should be addressed with a genetic counselor or physician.
Since diffuse gastric cancer is aggressive and hard to detect, people who carry CDH1 mutations are recommended to have a prophylactic gastrectomy which is a fancy way to say a preventative removal of the stomach before cancer develops around age 20. I don’t know about you, but I love to pig out from time to time! Removing someone’s stomach greatly impacts his or her quality of life. This impact can include strict limitations on meal size, abdominal pain, diarrhea, poor food absorption leading to malnutrition, and other unpleasant effects, but it comes along with a nearly complete reduction in stomach cancer risk.
As I mentioned earlier, CDH1 mutations are also associated with an increased lifetime risk for lobular breast cancer. This is a type of breast cancer that actually begins in the lobules of the breasts, rather than the milk ducts which is the more common starting site. This detail about a cancer diagnosis is important for genetic counselors and physicians to know, because it helps them determine which hereditary cancer syndrome (or syndromes) would be most likely, and what genetic test would be most appropriate to discuss with a family. As an aside, this is why genetic counselors often ask so many pesky questions about your personal and family history – I promise we’re not just being nosy!
With HDGC, there is a 39-52% lifetime risk for women to develop lobular breast cancer, and the average age at diagnosis is 53. Women with CDH1 mutations are offered the option of a prophylactic double mastectomy (removal of both breasts before cancer develops) or to begin a high-risk breast screening program, usually consisting of regular mammograms and breast MRIs beginning around age 35. But one of the issues with screening for lobular breast cancer is that it is very difficult to see using a traditional mammogram and more clinicians choose to screen patients with CDH1 mutations with breast MRIs for that reason.
This brings me to an incredibly difficult dilemma that many people with Lynch syndrome know all too well: choosing a lifelong high-risk screening program or preventive surgery. Removing body parts at high risk to develop cancer significantly reduces the lifetime cancer risk – but, as I mentioned earlier, this can come at a major cost to quality of life. Screening is less invasive, but unfortunately it’s not currently sensitive enough to catch all cancers in their earliest stages. This can leave some people who choose this option to feel like “ticking time bombs.” Choosing screening or preventive surgery is a very personal decision that people make based on their own mixes of personal experience, perception of risk, and other factors. Here’s the good news, though: they are not alone in their decision-making process. Genetic counselors and other health professionals can offer education, information, and guidance. And all these resources know that, in the end, the final decisions are best left to those whose lives will be directly impacted.
I hope I have been able to shed some light on one of the lesser known hereditary cancer syndromes. Lynch syndrome and the BRCA genes tend to command attention as they are a bit more common (as these rarer cancer syndromes go) and affect more families. Plus, who doesn’t want to “Save the Ta-Tas”?! This attention is well deserved, and I am glad to see the growing numbers of fundraisers and events dedicated to raising awareness about these syndromes. I know I’m a cancer genetic counselor, but it is still my hope that awareness can one day be raised for genetic testing and hereditary cancer syndromes as a whole. While the specific types of cancer associated with each syndrome differ, the issues that individuals face tend to be remarkably similar. For example, I believe that families affected with HDGC could benefit by being included in related support groups and events to let everyone who is affected know that they are not alone.
I know Georgia shares this sentiment with me, since she has cultivated such an inclusive blog to help support hereditary cancer syndromes and those navigating genetic testing. Let’s all share in the struggles and support of families impacted by hereditary cancer syndromes, so that awareness about medical guidelines and genetic testing can be raised for everyone.
To learn more about Hereditary Diffuse Gastric Cancer or to find support, check out:
Kaurah, P., & Huntsman, D. (2011, June 21). Hereditary Diffuse Gastric Cancer. Retrieved July 21, 2014, from http://www.ncbi.nlm.nih.gov/books/NBK1139/.
If you should have more questions about genetic testing and genetic counseling, please check out the National Society of Genetic Counselors website at www.NSGC.org
Thanks all for taking the time to read this blog! If you have suggestions please send them our way!
As always, you can email Georgia at firstname.lastname@example.org and me at email@example.com.
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Kelly Fulk, MS, CGC, was born and raised in Knoxville, TN and received her Bachelor’s degree in Psychology from Washington and Lee University in Lexington, VA. While studying at W&L, she played volleyball, worked on a local crisis hotline, and helped plan philanthropic events for Kappa Alpha Theta sorority. After graduating, she worked as a genetic counseling assistant for the Cancer Risk Program at UCSF Medical Center in San Francisco for two years before attending UC Irvine where she received her Master’s degree in genetic counseling. Kelly is currently an Oncology Genetic Specialist for Ambry Genetics. If she ever has free time in the future, Kelly would love to explore her wonderful new hometown of Richmond, VA.
Medical Disclaimer: Information and resources on ihavelynchsyndrome.com should not be used as a substitute for professional medical care. You are urged to work with your medical care provider for answers to your personal health questions.