1. Nalley, Catlin

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As the fifth-leading cancer in the world and the third-leading cause of cancer-related death, stomach cancer remains a significant issue (Dig Dis 2020;38(4):280-5). With nearly 1 million new cases annually worldwide, the World Health Organization (WHO) declared it a global health concern.

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Gastric cancer incidence varies depending on the geographic region. The highest incidence is seen in East Asia, some Eastern Europe, and South American countries. North America and Africa have the lowest occurrence rates. More than 70 percent of gastric cancer cases are in developing countries (Dig Dis 2020;38(4):280-5).


"Often, Western countries neglect to recognize the importance of this cancer. In countries such as the United States, over 26,000 new cases occur annually, a number that has been steadily increasing over the past 10 years," noted Vivian E. Strong, MD, FACS, the Iris Cantor Endowed Chair and Attending Surgeon at Memorial Sloan Kettering Cancer Center (MSKCC).


"Even more alarming, according to an article in JAMA 2010, is the fact that there is a 70 percent increase in the incidence of U.S. gastric cancer [in the bottom part of the stomach] in young adults under the age of 40 years old. The reasons for this are still not fully understood," she continued. "In addition, there has been a seven-fold increase in the incidence of GEJ, or gastroesophageal junction, cancers in U.S. adults. This is likely related to issues of obesity and reflux disease that are so prevalent in Western countries."


Given the impact of this disease, it is imperative that clinicians are aware of the risk factors and preventive interventions. Ongoing efforts to improve early detection, as well as continued treatment advancements, are crucial to address stomach cancer around the world.


Risk Factors & Prevention

There are a number of known risk factors for gastric cancer, both modifiable and nonmodifiable. These include genetic, environmental, and behavioral elements.


Approximately 10 percent of all gastric cancers are familial in origin, according to the NIH. One example is hereditary diffuse gastric cancer, which is known to be caused by a germline mutation in the CDH1 mutation, according to Strong, who is Professor of Surgery and Associate Dean at Weill Cornell Medical College.


"At Memorial Sloan Kettering Cancer Center, we have particular expertise in this form of familial gastric cancer, having operated on well over 100 such patients and following close to 200," she said. "Families who have this mutation, along with a family history of gastric cancer or lobular breast cancer, have a 55-70 percent lifetime risk of developing invasive signet ring cell gastric cancer, a very aggressive form of gastric cancer for which treatments are not well-established.


"We also know that other genetic mutations, such as the CTNNA1 germline mutation, are associated with patients who have familial gastric cancer," she added. "There are a number of other genetic mutations that are associated with gastric cancer and other cancers, such as FAP or GAPPS, and our understanding of these mutations and their relative risk continues to grow with research efforts that are ongoing at our institution and others."


Environmentally, Helicobacter pylori (H. pylori), which has been labeled a Class 1 carcinogen by the WHO, may be the most important causative factor, Strong said. "Studies have demonstrated that having untreated H. pylori over a 10-year period increases one's risk of developing gastric cancer (odds ratio) by nearly six-fold.


"From a behavioral perspective, obesity and smoking are perhaps the most serious culprits of developing gastric and many other types of cancer," Strong explained. "Other modifiable factors, such as a high-salt diet, pickled food, and foods with nitrites, such as charred meats, are also known factors to increase one's risk of developing gastric cancer."


Strong noted that a healthy diet of vegetables and high-fiber foods appear to have protective qualities. The best preventative measure to mitigate gastric cancer is a healthy lifestyle that includes moderate exercise, as well as a diet with plenty of vegetables and fiber, she suggested.


Looking to the Future

To address the burden of stomach cancer and increase survival, ongoing treatment advances as well as efforts to improve early detection are needed.


"The best way for us as a nation to improve survival from gastric cancer is to discover novel and improved treatment strategies for those diagnosed with locally advanced gastric cancer and to raise awareness in the public to this global health crisis to improve early detection through endoscopic screening," Strong emphasized.


The past decade has seen a number of developments in multimodality therapy for gastric cancer. This includes the landmark FLOT trial, which has improved survival for patients who need perioperative chemotherapy, according to Strong. Additionally, novel immunotherapies have led to remarkable treatment responses among eligible patients.


A variety of research is currently underway that holds promise for improved stomach cancer outcomes, including better selection of patients who are more susceptible to targeted therapy. At MSKCC, Strong noted, it is becoming routine to test for molecular markers such as HER-2, PD-1, MSI, and EBV.


Other areas that hold promise, according to Strong, include:


* understanding the microbiome and its complex interaction with tumorigenesis;


* clinical trials aiming to improve and lengthen the lives of those with stage IV gastric cancer; and


* the complex interaction of the immune system with the development and regression of the tumor.



A commitment from all stakeholders is crucial to the success of these efforts. At MSKCC, there is a group of surgeons, medical oncologists, gastroenterologists, geneticists, pathologists, and immunologists who are "dedicating their lives to improving the outcomes for patients with gastric cancer," noted Strong.


"We have formed dedicated gastric tumor boards and dedicated gastric research meetings with physicians and scientists who are determined to make a change and help gastric cancer patients," she concluded. "It is clear that when significant interest and resources are directed to solving a problem, remarkable achievements are possible."


Catlin Nalley is a contributing writer.


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