TCGA's Study of Gastric Adenocarcinoma
What is stomach cancer?
Stomach cancer, the 16th most common cancer in the United States, arises in the cells that line the stomach. The number of new cases of stomach cancer in the United States was estimated to be 24,590 in 2015.1
The incidence of stomach cancer varies widely depending on genetic and environmental factors. Stomach cancer is more likely to affect men, older patients, and those with a family history of the disease. In the U.S., the risk is also higher for Hispanic Americans, African Americans and Asians/Pacific Islanders than for non-Hispanic whites. Globally, the incidence varies by geographic region.
Environmental risk factors for stomach cancer include smoking, obesity, and a diet high in smoked, salted, or pickled foods.2 Another risk factor is bacterial or viral infection. Infection by the bacteria Helicobacter pylori in the stomach appears to be a major cause of stomach cancer, as long-term infection with this bacterium can lead to inflammation and pre-cancer development. Research also indicates that stomach cancer is associated with infection with Epstein-Barr virus, a virus of the herpes family that is best known for causing mononucleosis.
The rates for new stomach cancers in the U.S. has been falling by 1.5% each year on average over the last 10 years.3 However, stomach cancer tends to be diagnosed at an advanced stage because it is often undetected until major symptoms appear, leading to a low 5 year survival rate of 17.9% between 2005 and 2011.
What have TCGA researchers learned about stomach cancer?
- The disease can be categorized into four genomic subtypes of stomach cancer.
- The Epstein-Barr virus (EBV) subtype, comprised of 9% of cancers studied, had:
- Amplified expression of genes that suppress the immune response, possibly preventing the immune system from acting against EBV
- Frequent alterations in the PIK3CA gene, which codes for a component of PI3-kinase and may be targeted by PI3-kinase inhibitors
- The microsatellite instability (MSI) subtype made up 22% of tumors and was:
- Characterized by an elevated rate of mutations
- A genomically stable (GS) subtype (20% of tumors studied) was distinguished by few structural changes in the chromosomes
- A chromosomal instability (CIN) subtype (5% of tumors studied):
- Demonstrated high chromosomal instability
- Increased expression of receptor tyrosine kinases (RTKs) including VEGFR2, suggesting that RTK inhibitors like the VEGFR2 targeting antibody, ramucirumab, may be effective
1American Cancer Society. Cancer Facts and Figures 2015. Atlanta: American Cancer Society, Inc. 2015.
2American Cancer Society. What are the Risk Factors for Stomach Cancer? American Cancer Society. www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-risk-factors. Accessed 2015.
3Howlader N, Noone AM, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER web site, April 2015.