According to the World Health Organization, Stomach cancer is considered one of the third lethal cancers affecting people globally. Also known as Gastric cancer, it is divided into two classes; gastric cardia cancer and non-cardia gastric, i.e., cancer developing in the top of the stomach where it meets the esophagus and cancer that occur in other areas of the stomach. Majority of stomach cancer develops from the lining of the stomach and are hence called adenocarcinoma. The pre-cancerous changes that can occur before cancer develops can often go undetected without presenting any symptoms. It is therefore important to understand the risk factors associated with the development of the disease and to have screening tests particularly for the high-risk groups such as those with gastric cancer in their family.

Research also indicates that an infection with H.pylori also increases the risk of developing gastric cancer. However, if detected at an early stage, there is much hope, but the advanced stage of the disease presents poor outlook. Surgery is recommended for localized stomach cancer and mostly individuals with early-stage disease benefit from this. Although chemoradiation and chemotherapy are recommended to prevent recurrence, only around 10% of individuals show improved cure and with increased toxicity. It is hoped that the current advances with genomics can help make a difference with the potential for the development of effective novel therapeutic treatments for better survival of the affected individuals.

 Understanding the Risk Factors

While dietary habits such as food that is heavily salted, smoked or pickled increase the risk of gastric cancer, genetic linkage also appears to play a role in some cases. Individuals with certain genetic diseases such as familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer and Peutz Jeghers syndrome are also predisposed to developing it. A hereditary diffuse gastric cancer (HDGC) is an inherited genetic problem with a mutation detected in CDH1 gene presenting an increased risk of gastric cancer. Families who had several cases of gastric cancer are recommended to have genetic testing to determine the presence of this genetic mutation.

Association with Helicobacter Pylori

H.pylori is a spiral-shaped bacterium that has coexisted with humans for centuries and according to the Centers for Disease Control and Prevention around one-third of the population harbors the bacterium. As the bacteria are attached to the epithelial cells, an inflammatory response is induced which implicates epithelial cell damage and carcinogenesis. It is therefore recommended that H.pylori infection should be diagnosed and treated particularly among those with a family history of gastric cancer and among communities with high incidence of cancer. In a randomized clinical trial carried out in China, where the rates of gastric cancer are very high, it shows that treatment with antibiotics to eradicate H.pylori helps lower the incidence rate of gastric cancer.

Primary Prevention with Screening Programs

The primary prevention of gastric cancer is possible only with screening programs particularly for the high-risk groups. Although there are no established screening programs in the United States where the incidence rate is low, Japan has successfully had screening programs for more than 50 years where it is much more prevalent. The screening tests include double-contrast barium radiographs and upper endoscopies that can detect gastric cancers in over 90% of the cases. In recent years, studies have confirmed the use of blood test for screening of gastric cancer which detects low levels of enzyme serum pepsinogen I/II ratio, however, this requires to be verified as it is still under the early stage of testing.

Predicting Stomach Cancer with Genetic Study

The genomic technologies were used to comprehend intestinal metaplasia (IM) which is a risk factor for gastric cancer and it is estimated that those with IM are six times more likely to develop gastric cancer. The co-lead investigator and Professor Patrick Tan said; ‘Previous genetic studies on IM have mainly focused on patients who were already diagnosed with stomach cancer but these are limited in their ability to predict who are likely to develop the disease and how the disease will progress.” This is one of the first studies to map out the genetic changes among those with IM in a cohort of stomach cancer-free individuals which is hoped to better predict the development of the disease. This research can then help detect the biomarkers to be applied in the clinical settings to identify individuals presenting a high risk of progression to stomach cancer.

Various Progressions in the Management of the Disease

In the early stage, stomach cancer has the potential to metastasize and the lymph node metastasis is considered an important prognostic factor. The treatment of gastric cancer has now progressed rapidly with the development of surgical techniques and the instruments used. The different endoscopic resection techniques are divided into two main categories; the endoscopic mucosal resection and endoscopic submucosal dissection. From the results of experimental and clinical studies, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were developed.  

Hyperthermia increases the antitumor activity and penetration of chemotherapeutics. Various randomized studies observed the benefits of adjuvant intraperitoneal chemotherapy after curative gastric cancer resection and the reports exhibited better survival of these patients. Trastuzumab is a monoclonal antibody that blocks human epidermal growth factor (HER) 2 function which is related to gastric carcinoma. Although the exact mechanism of trastuzumab is not entirely known, mechanisms such as blocking the cycle progression of the cell, cell signaling pathways, induction of anti-angiogenesis effects and increasing receptor turnover by endocytosis have been reported. Also, a phase III international multicenter RCT compared the safety and the effect of trastuzumab with chemotherapy and the survival rate shows to be significantly longer than with standard chemotherapy.

Advances and Future Directions

The current advances in the cancer genomics are significantly making a difference in the molecular characterization of different forms of cancer. The application of next-generation sequencing technology to gastric cancer has helped understand the complex genomic landscape of this cancer. This then has resulted in the development of novel genomically based molecular classification systems and with the discovery of new driver gene mutation that was not previously known. This genomic data in the future has the potential to both improve the treatment and the survival of the affected individuals.