What is diffuse stomach cancer?
Diffuse stomach cancer is a specific type of stomach cancer, sometimes also called “signet ring cell gastric cancer” or “linitis plastic.” The word “diffuse” is used because this cancer tends to affect much of the stomach, rather than staying in 1 area of the stomach.
What is hereditary diffuse stomach cancer?
Hereditary diffuse stomach cancer (also known as Hereditary Diffuse Gastric Cancer – HDGC) is a rare inherited condition associated with an increased risk of stomach cancer. This means that the cancer risk and other features of HDGC can be passed from generation to generation in a family/ whānau. The gene most commonly associated with HDGC is called CDH1. A mutation (alteration) in the CDH1 gene gives a person an increased risk of developing stomach cancer and other cancers associated with HDGC. When the CDH1 gene is working properly it suppresses tumour growth, but when it doesn’t function normally it allows the uncontrolled growth of cells, including cancer cells, to occur.
Researchers believe that other genes, including CTNNA1, may be associated with HDGC.
Hereditary diffuse stomach cancer in New Zealand
New Zealand has a disproportionately large number of HDGC because the CDH1 gene has been found to be carried in a number of Māori whānau. In 1997 University of Otago geneticists discovered a hereditary mutation in the CDH1 gene was responsible for an unusually high number of cases of diffuse gastric cancer in The McLeod whānau – of which musician Stan Walker is a member.
Research led by Professor Parry Guilford at The University of Otago along with Maybelle Mcleod and the team at Kimihauora Health and Research Clinic’s (Mt Maunganui) work in understanding the role of variants (mutations) in the CDH1 gene in familial stomach cancer and the subsequent development of a genetic test, has dramatically reduced the number of deaths from this form of inherited cancer.
This work has been taken a stage further when Professor Guilford and Dr Karyn Paringatai developed new guidelines insisting that testing for the CDH1 become more easily accessible. Previously, the guidelines were largely based around the number of cases of this cancer in a family. The new guidelines recommend the whānau of any Māori person who has been diagnosed with diffuse stomach cancer be encouraged to have a genetic test, regardless of any other family history.
Diagnosis of Hereditary Diffuse Stomach Cancer
Guidelines for the diagnosis of HDGC syndrome have been proposed, but may change over time as more is learned about this condition. Currently, the diagnosis of HDGC is suspected, and CDH1 genetic testing should be considered if a person or family meets any of the criteria listed below:
- Whānau of any Māori person who has been diagnosed with diffuse stomach cancer
- Families with 2 or more cases of stomach cancer, with at least 1 being diffuse gastric cancer
- A person diagnosed with diffuse gastric cancer before age 40
- Personal or family history of both diffuse gastric cancer and lobular breast cancer, if at least 1 person was diagnosed before age 50
- Families with 2 or more cases of lobular breast cancer diagnosed before age 50
- A person diagnosed with multiple different lobular breast cancers before age 50
- A person with diffuse gastric cancer and a personal or family history of a cleft lip or cleft palate
Genetic testing for mutations in the CDH1 gene is available. However, only about 20% to 30% of families that appear to have HDGC will have a mutation found in the CDH1 gene. Therefore, both clinical and genetic aspects must be considered in counseling individuals about the potential for their family to have HDGC. Talking with a specialist who has training in genetic diseases and conditions, called a genetic counselor or geneticist, who is familiar with the syndrome is recommended.
If your whanau carries the CDH1 gene mutation the team at University of Otago has written this booklet/ passport to help patients (urihaumate) and their whānau with familial gastric cancer to understand the reasons for the decisions made around their care so that they can actively participate in those decisions.
The aim of this booklet is to inform urihaumate and whānau about their disease (mate) and to ensure good quality care for urihaumate with familial gastric cancer.
Risks of developing Hereditary Diffuse Stomach Cancer
Not everyone who inherits a gene mutation for HDGC will develop cancer. In people who have a mutation in the CDH1 gene, the lifetime risk for diffuse gastric cancer is estimated to be 67% to 70% for men and 56% to 83% for women by age 80.
Women with a mutation in the CDH1 gene have about a 39% to 52% risk of developing lobular breast cancer by age 80. Although some earlier studies suggested a possible link to risks of colon and/or rectal cancer, the current findings suggest that there is likely no increased risk for these cancers in people with an inherited CDH1 mutation.
Treatment/ Risk reduction
Given the increased risk of cancers associated with germline mutations in CDH1, it is recommended that people found to have this genetic mutation (called carriers) discuss the most appropriate strategies to reduce cancer risks with their health care team:
Endoscopic tests are when a thin, lighted tube is guided through the body’s gastrointestinal system to look for cancer. Although a baseline upper endoscopy exam (esophagogastroduodenoscopy or EGD) is recommended for carriers, previous studies have shown that screening endoscopy exams often miss early-stage diffuse gastric cancers.
Therefore, since endoscopic surveillance can be ineffective for preventing or detecting early-stage diffuse gastric cancers, individuals with a germline CDH1 mutation should consider having their stomach surgically removed, also known as prophylactic total gastrectomy, even if their endoscopy is normal. This type of surgery is the only proven effective way to prevent diffuse gastric cancer in individuals with HDGC.
However, it is important to know that surgical removal of the stomach results in permanent changes to the digestive tract and can be associated with long-term side effects. It is very important for each patient to talk with their doctor about what tests and procedures would be appropriate for their individual care.
People who decide not to have surgery to remove the stomach may consider an intensive surveillance schedule with their doctor. Both the surgical and endoscopic management of people with known or suspected HDGC are best performed in centres with expertise in care of people with this syndrome.
If you have any concerns or want to discuss your situation with Maybelle Mcleod and the team at Kmihauora Health and Research Clinic on email@example.com.
In 2012, Isaia tested positive for the CHD1 gene mutation. 10 years on, Isaia and his wife Kelly share their journey with us: