Hereditary gastric cancer
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Gastric cancer is the third leading cause of cancer-related deaths worldwide, with a 5-year survival rate of only 20%. Although the majority of cases are sporadic, 1%-3% can be attributed to inherited cancer predisposition syndromes. In families with an autosomal dominant inherited predisposition to diffuse gastric cancer, germline E-cadherin/CDH1 mutations have been identified. The cumulative risk of developing gastric cancer for CDH1 mutation carriers by age 80 is 70% for men and 56% for women. Female mutation carriers also have a 42% risk of developing lobular breast cancer by age 80. However, not all individuals meeting clinical criteria for hereditary diffuse gastric cancer syndrome (HDGC) have a germline CDH1 mutation, and those who do may not exhibit similar clinical outcomes in terms of age of diagnosis or cancer types.
The following are environmental factors that increase the risk of developing gastric cancer:
Infection caused by Helicobacter pylori (H. pylori).
Regimen of food.
Diet has an impact on the regional differences in the incidence of gastric cancer.
The consumption of salt-preserved foods may elevate the likelihood of developing gastric cancer in individuals.
Elevated risk of gastric cancer may result from inadequate consumption of fruits and excessive consumption of processed, grilled, or barbequed meats/fish.
Effects of migration.
The risk of developing gastric cancer may also be influenced by the effects of migration, such as when individuals move from a region with a high risk of gastric cancer to one with a low risk, or vice versa.
Research has shown that the occurrence of gastric cancer among immigrants is highly associated with the occurrence of gastric cancer in their adopted country within one or two generations.
The utilization of tobacco.
Consumption of alcohol.
There is increasing evidence linking obesity to gastroesophageal reflux disease (GERD).
Disparities based on race and ethnicity.
Criteria for germline genetic testing are available for the genes linked to gastric cancer and/or gastric polyps, including CDH1, CTNNA1, APC, STK11, SMAD4, and the Lynch syndrome genes (MLH1, MSH2, MSH6, EPCAM).
Other genetic syndromes that increase the risk of gastric cancer will be examined, along with recently identified changes in other genes (CTNNA1, DOT1L, FBXO24, PRSS1, MAP3K6, MSR1, and INSR) that could impact susceptibility to gastric cancer and age-related penetrance.