Stomach cancer is the second leading cause of cancer related deaths worldwide and in India, the fourth in the list of the most common cancers. As per the US National Institutes of Health (NIH) close to ten percent of stomach cancer cases have a familial origin. Having a first degree relative such as father, mother, brother or sister with stomach cancer increases the risk of developing stomach cancer.
While gene mutations have been linked to stomach cancer in some people, the exact genetic factors are not fully understood. Scientists believe a combination of environmental and genetic factors could be responsible for familial stomach cancer.
Some of the inherited conditions that increase stomach cancer risk include:
Hereditary diffuse gastric cancer (HDGC):
This is an inherited, rare condition that increases risk of stomach cancer caused by a mutation in a gene known as CDH1.
Diffuse gastric cancer also known as or “linitis plastica” or“signet ring cell gastric cancer” affects almost the entire stomach rather than any one specific area in the stomach. According to the NIH, diffuse gastric cancers account for 20 percent of stomach cancers and HDGC is responsible for a small amount of these cancers. Women diagnosed with HDGC are at an increased risk of developing breast cancer.
Diagnosis of HDGC is made if any one criteria listed below are met apart from recommending CDH1 genetic testing:
- Families which have two or more stomach cancer cases with one of them being diffuse gastric cancer
- Diagnosis of diffuse stomach cancer before the age of 40
- Individual and/or family history of lobular breast cancer and diffuse stomach cancer with at least one person being diagnosed before 50 years of age
- Lobular breast cancer diagnosis in the family before age 50
Although genetic testing for CDH1 gene mutation is available, only about 20 to 30 percent of families with possible HDGC are found to have CDH1 gene mutation. Talking to a cancer specialist well versed in genetic conditions is the best way to understand if you are at risk for developing stomach cancer.
Lynch syndrome:
Lynch syndrome (earlier called hereditary non-polyposis colorectal cancer) is an inherited condition which increases colorectal, stomach and other cancers. The genes implicated in Lynch syndrome include MLH1,MSH2, MLH3, PMS1, MSH6, TGFBR2 and PMS2.
Familial adenomatous polyposis:
Familial adenomatous polyposis or FAP is linked to mutations of the APC gene and is characterised by the development of multiple polyps typically in the colon but can involve the intestine and stomach as well. People with FAP have a higher risk of developing both colorectal and stomach cancer.
BRCA gene mutations:
BRCA1 and BRCA2 are inherited gene mutations associated with an increased risk of breast cancer. Mutations in these genes are also linked to higher stomach cancer risk.
Li-Fraumeni syndrome:
Mutation in a tumor suppressor gene known as TP53 causes Li-Fraumeni syndrome which raises the risk of some cancers such as stomach cancer.
Peutz-Jeghers syndrome:
In this condition, polyps develop in the intestines, stomach, and other areas including lungs, nose, and bladder. The stomach polyps are called hamartomas and can cause problems such as blockage or bleeding in the stomach. PJS increases the risk of many cancers including stomach, pancreas, intestine and others.