Banner

Gastric Cancer and Genomic DNA Sequence

Gastric cancer, cancer of the lining of the stomach where food is first digested, is a dangerous disease which is difficult to diagnose early. This cancer, like all other cancers, has distinct pathologically distinguishable stages. All stages combined, the 5-year survival rate of gastric cancer is about 32%.; however, if gastric cancer has spread to distant locations from the site of original tumor (late stage 3 or stage 4), the 5-year survival rate is only 6%. 
 
Worldwide, gastric cancer is one of the most common cancers, afflicting more than 1 million new patients every year, which is about 5.7% of all cancer diagnoses combined. In some countries, younger individuals are at a heightened risk of getting gastric cancer. High risk regions include Eastern Europe, Central and South America, and Eastern Asia. Gastric cancer is a leading cancer in Bangladesh; in male it ranks just after lung cancer, the most frequent type of cancer worldwide.
 
There are several risk factors for gastric cancer, including smoking, consumption of alcohol and coffee, high meat consumption, obesity, gastric ulcer, gastro-esophageal reflux disorder (or GERD), infection with Helicobacter pylori infection that commonly produces chronic indigestion and even GERD, and certain genetic factors chief among which is the inherited null mutation in GSTM1 gene and/or the CDH1 gene. Sixteen different DNA sequence variants of CDH1 gene have been shown to be associated with increased susceptibility to gastric cancer. Other less certain genetic variants have been identified as being associated with higher frequencies of gastric cancer, and a genomic DNA sequence can identify the presence or absence of several such susceptibility variants in the genome.  
 
Males of South East Asian countries are at a higher risk than average of dying of gastric cancer. 87% of gastric cancer patients in Bangladesh were found to have untreated H. pylori infection in the stomach.
 
How does one determine whether genetic risk factors associated with gastric cancer is present in a person? The fastest way today for gastric cancer disease prediction is the typing of Single Nucleotide Polymorphism (or SNP) associated with gastric cancer. Saliva samples are collected in a special vial available from Genofax or other companies. These are mailed to a central laboratory where the person’s DNA is analyzed for the presence or absence of certain SNPs. Then these are analyzed using computer models to assess the risk. A problem with this method, however, is that most gastric cancer association with SNPs have been carried out with ethnic populations who are genetically only distantly related to the people of southeast Asia. Therefore, it is unclear whether the results will apply with a high degree of confidence. Genofax is trying to reconcile these problems with advanced machine-learning prediction methods.
 
The second method for gastric cancer disease prediction, as indicated above, involves genome sequencing. The same method of sample collection is conducted as described for SNP typing, but in this case the DNA sequencing is more involved, which Genofax is able to do, and subsequent analysis uses advanced computational methods such as machine-learning prediction. From these data, a risk score is computed. Again, this suffers from a lack of primary data on gastric cancer’s association with DNA sequences in ethnic southeast Asian or Bangladeshi or populations of the Indian subcontinent. The same weakness exists for African and near east Asian populations. Nonetheless, the genomic DNA sequencing is more reliable than purely SNP based methods.
 
As is indicated above, H. pylori infection is a major cause of gastric cancer; the presence of H. pylori can be detected by a standard blood test as well as by a ‘metagenomic’ test. Metagenomic test involves providing a stool sample in special sample collector obtained from Genofax. This is then mailed to a metagenomic DNA sequencing laboratory, which isolates microbial DNA from the stool samples and performs advanced machine-learning prediction analysis. The results should not only establish whether there is H. pylori infection, but also the relative proportions of other microbes in the stool sample. This method provides more information on the general gut-health of the person than is ever possible from the simple blood test, which only provides a yes/no answer to whether a H. pylori infection ‘might’ be present—this is because the test is an immunological test, and therefore has a high rate of false positivity. In people with previous H. pylori infection which was resolved at the time of blood draw may falsely provide a positive result. 
 
While genetic predisposition increases the risk of gastric cancer, the cancer itself is produced by chance mutation in the stomach lining cells, which first make benign tumors, which then, upon accumulating further mutations, become malignant cancer. Some mutations that drive gastric cancer have been identified, but, interestingly, the driver mutations in ethnic Asian populations are different from the driver mutations of gastric cancer in ethnically European populations. However, the ethnic Asian populations that were studied were from Vietnam, China, Singapore and South Korea; no such study has been conducted on Indian or Bangladeshi populations.
 
Whole genome sequencing of gastric cancer tumor biopsies can be conducted by Genofax, and the data can be analyzed by advanced machine-learning methods to identify known driver mutations that may or may not be present in the tumor samples. Depending on the result, individualized treatment can be discussed with oncologists (physicians who treat cancer). However, there is a great unmet need to identify currently unknown drivers of gastric cancer  in southeast Asian/African population through genome sequencing of tumors, and this is an important goal of the Genofax research team.
 
Healthy dietary habit including food rich in dietary fibers and fresh vegetables, less fat and meat or fried food, lack of smoking, prompt and adequate treatment of gastric ulcerative disorders initiated by H. pylori through the use of appropriate antibiotics, weight control through regular exercise in all ages, and improvements in early diagnostic technologies, all appear to contribute to a decreasing trend in the incidence of gastric cancer worldwide, except in the younger population. It is unclear why the incidence of gastric cancer is increasing among the younger population. One possible factor is the relatively higher weight of today’s younger population combined with lack of exercise and high meat diet. However, other factors may be present.
 
If you are young and you smoke, stop smoking; if you have frequent indigestion, consult your physician to possibly diagnose H. pylori infection and if so, get it treated with antibiotics; do regular exercise to reduce body weight; eat better so that you have better gut health; if you have a history of upper GI tract cancer in your family, check out your DNA sequence to assess your genetic susceptibility. Assessing your microbiome could also help guide you towards a healthier life.

Comments (0)