It is estimated that approximately 15% of stomach cancers occur in patients with a family history of stomach cancer. Some of these cases are known to be caused by familial or inherited cancer syndromes. These genetically inherited syndromes include Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Familial Adenomatous Polyposis (FAP), Li-Fraumeni Syndrome, Peutz-Jeghers Syndrome (PJS), Gastric Adenomatous Proximal Polyposis Syndrome (GAPPS), and Hereditary Diffuse Gastric Cancer (HDGC). It is also thought that patients who carry the BRCA1 and BRCA2 gene mutations, which increase the risk of breast and ovarian cancer, may also have an increased risk of developing stomach cancer.
The Oncologist: Familial Gastric Cancers
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
HNPCC, also known as Lynch syndrome, increases a patients’ risk of developing various cancers, including cancer of the colon and stomach. It is estimated that 3 out of every 100 cases of colon cancer are caused by Lynch Syndrome. Other cancers associated with Lynch syndrome include ovarian, endometrial, kidney, biliary tract, and pancreatic cancer. Lynch syndrome has an autosomal dominant pattern of inheritance. Most cases of HNPCC are caused by a mutation in the MLH1 or MSH2 gene. However at least five other genes can cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2.
Dana Farber Cancer Institute Lynch Syndrome Center
Familial Adenomatous Polyposis (FAP)
FAP is a familial syndrome characterized by thousands of polyps that develop in the intestinal tract of affected patients. These polyps significantly increase the risk of developing colon cancer. Because FAP may also cause polyps to grow in the stomach, the risk of stomach cancer increases in patients with FAP. A mutation in the APC gene causes FAP.
The Columbia Hereditary Colorectal Cancer Center
Li-Fraumeni Syndrome is caused by a mutation in the TP53 gene. The syndrome creates an increased risk of several types of cancer, including the development of stomach cancer at a relatively young age.
Li-Fraumeni Syndrome Association
Peutz-Jeghers Syndrome (PJS)
Caused by mutations in the STK1 gene, Peutz-Jeghers Syndrome (PJS) can create polyps in the stomach and intestines, the nose, the airway of the lungs and the bladder. The polyps in the stomach and intestines are referred to as hamartomas and can cause problems like bleeding or intestinal blockage. Dark freckle-like spots can also appear on the lips, inner cheek and other areas as part of the syndrome. An increased risk of cancers of the breast, colon, pancreas, stomach and other organs occurs in people with PJS.
National Library of Medicine Definition
American Society of Clinical Oncology
Gastric Adenomatous Proximal Polyposis Syndrome (GAPPS)
GAPPS causes many small bumps, called polyps, to form on the inside lining of the stomach. Polyps can be benign, meaning they cannot spread to other parts of the body. Polyps can also turn into cancer, meaning they can spread to other parts of the body.
Because GAPPS runs in families, we know that changes in a specific part of the APC gene are essential in GAPPS. Not all people with changes in the APC gene develop GAPPS similarly. Some people may develop GAPPS later in life than others. It is important to continue going to your doctor to monitor the development of GAPPS.
Hereditary Diffuse Gastric Cancer (HDGC)
Unlike HNPCC and FAP, HDGC is predominantly associated with the development of stomach cancer. HDGC also increases the risk of developing lobular breast cancer. In patients from HDGC families, stomach cancer may grow at a young age. The HDGC syndrome is an autosomal dominant inherited condition. This condition is known to be caused by mutations in the CDH1 (E-cadherin) gene. Researchers believe mutations in other genes yet to be identified are associated with this syndrome.
National Cancer Institute Patient Resources for HDGC
BRCA1 and BRCA2 Gene Mutations
A higher rate of stomach cancer may appear in people who carry BRCA1 or BRCA2, mutations of the inherited breast cancer genes.
BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing. Release Date: August 2019
Clinical Guidelines for Hereditary Stomach Cancer Syndromes
The American College of Gastroenterology Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes.
Hereditary Diffuse Gastric Cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.
References and Sources
Shah MA, Pinheiro N, Shah BM. 100 Questions & Answers About Gastric Cancer. Sudbury, MA: Jones and Bartlett Publishers, 2008.
Mayo Clinic Health Information website. Accessed 06/27/2011.
American Cancer Society website. Accessed 06/27/2011 and 10/13/2015.
U.S. Preventive Services Task Force
GAPPS information was originally published by the National Cancer Institute.