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) 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.
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.
Familial Adenomatous Polyposis (FAP)
FAP is a familial syndrome that is 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 is increased in patients with FAP. FAP is caused by a mutation in the APC gene.
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.
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.
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 develop 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 that mutations in other genes yet to be identified are associated with this syndrome.
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.
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.