An estimated 1-3% of cases of stomach cancer are caused by inherited syndromes. Hereditary Diffuse Gastric Cancer (HDGC) is an inherited cancer syndrome that leads to an increased risk for both diffuse gastric cancer and lobular breast cancer. Patients who inherit the genetic mutation for HDGC are at high risk of developing stomach cancer at a young age.
History of HDGC
In 1964, stomach cancer was noted in a Maori tribal family in New Zealand, following an autosomal dominant pattern of inheritance. CDH1 gene mutations were first described in patients from three Maori families in 1998. At this time, the International Gastric Cancer Linkage Consortium (IGCLC) was formed, and the name “Hereditary Diffuse Gastric Cancer” was introduced. Families with multiple cases of diffuse gastric cancer, lobular breast cancer, or both may be affected by hereditary diffuse gastric cancer syndrome.
Diffuse Gastric Cancer
HDGC leads to cancer called diffuse-type, signet ring cell gastric adenocarcinoma. These signet ring cells appear as isolated cells or in small clusters in the lining of the stomach. Unfortunately, the diffuse type of gastric cancer associated with HDGC is challenging to diagnose because the tumor is not visible on upper endoscopy (looking into the stomach with a small camera). For this reason, most cases of diffuse gastric cancer are diagnosed at late stages (III or IV) and associated with a lower survival rate.
Women from HDGC families should be followed by oncologists or breast surgeons and have clinical breast exams regularly. Screening with yearly breast MRI, which can be combined with mammograms, is recommended starting at age 30. There is a possible role for preventive hormone-blocking medications to reduce the risk of lobular breast cancer in CDH1 mutation carriers. If there are many cases of breast cancer in the family, prophylactic mastectomy may also be considered, but mastectomy is not routinely recommended.
Future of HDGC
Research on the genetics, diagnosis, and treatment of HDGC is ongoing. Centers of Excellence have been established worldwide, and experts from the International Gastric Cancer Linkage Consortium continue to work together to develop new guidelines and recommendations for patients and families affected by HDGC. The next IGCLC HDGC Guidelines Meeting to discuss updates to the guidelines will take place March 16-18th 2019 in Wanaka, Aotearoa New Zealand. You can connect directly with Dr. Parry Guilford at the University of Otago to inquire about attending.
Clinical Guidelines for Hereditary Stomach Cancer Syndromes
Establishing a Center of Excellence for hereditary diffuse
gastric cancer syndrome
Published January 3, 2019, in the Journal of Surgical Oncology. You may request access to the article from one of the co-authors Dr. Jeremy Davis.
Medical Centers for the treatment and care of Hereditary Diffuse Gastric Cancer
Clinical Trials and Research Studies for Hereditary Stomach Cancer
Researchers at the National Institutes of Health (NIH) seek individuals with hereditary stomach (gastric) cancer or who are at risk for developing stomach cancer because of a genetic (inherited) condition. Hereditary stomach cancers run in families, meaning they are passed down from one generation to the next.
Ford JM. Inherited susceptibility to gastric cancer: advances in genetics and guidelines for clinical management. American Society of Clinical Oncology Educational Sessions. 2002:116-125.
Huntsman DG, Carneiro F, Lewis FR, MacLeod PM, Hayashi A, Monaghan KG, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. The New England Journal of Medicine. June 2001;344(25):1904-1909.
Francis WP, Rodrigues DM, Perez NE, Lonardo F, Weaver D, Webber JD. Prophylactic laparoscopic-assisted total gastrectomy for hereditary diffuse gastric cancer. Journal of the Society of Laparoendoscopic Surgeons. 2007;11:142-147.
Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, et al. Familial gastric cancer: overview and guidelines for management. Journal of Medical Genetics. 1999;36:873-880.