Identifying stomach cancer risk

7 Aug 2018

Genetic and epigenetic testing of samples from people with cellular changes to the stomach lining could help predict their risk of developing cancer

Genetic sequencing of gastric samples from people with intestinal metaplasia (left) could help identify those who are more at-risk of developing gastric cancer (right).

Genetic sequencing of gastric samples from people with intestinal metaplasia (left) could help identify those who are more at-risk of developing gastric cancer (right).

© Supriya Srivastava, NUHS

People with a potentially precancerous condition are more at risk for developing gastric cancer if their stomach lining samples show specific chromosomal alterations. Genetic testing of these samples can also improve detection of a cancer-causing bacterial infection, according to research published by Singaporean scientists.

Intestinal metaplasia is a condition, usually without symptoms, in which the cells lining the stomach change to resemble intestinal cells. It occurs in an estimated one quarter of the world’s population, and has the potential to develop into gastric cancer. It is typically diagnosed through routine endoscopic examinations of the gastrointestinal tract, but these tests are expensive and invasive, so surveillance endoscopies are only cost-effective in countries where gastric cancer rates are high.

Patrick Tan of A*STAR’s Biomedical Research Council, and colleagues, investigated the genetic and epigenetic changes that occurred over a period in people with intestinal metaplasia. They studied stomach tissue samples, showing different stages of the condition, from almost 150 cancer-free people involved in the Gastric Cancer Epidemiology Program, led by Khay Guan Yeoh of the National University Hospital Singapore, which conducted surveillance endoscopies in almost 3,000 Singaporeans over several years.

“Our data suggest that patients with intestinal metaplasia exhibiting telomere shortening and chromosomal instability are significantly more likely to progress to gastric cancer,” says Tan. Telomeres are structures that protect the ends of chromosomes from deterioration. Intestinal metaplasias showing normal genetic patterns were more likely to revert back to healthy gastrictissue.

The team also found that genetic sequencing of gastric tissue could identify infection by Helicobacter pylori bacteria more accurately than microscopic examinations. H. pylori infection of the stomach is common and is usually asymptomatic, but it can lead to stomach ulcers and is a risk factor for the development of intestinal metaplasia and gastric cancer in some people. Treating it early with antibiotics is important and can delay progression of intestinal metaplasia to gastric cancer.

Microscopic detection of H. pylori infection is challenging in samples with concurrent intestinal metaplasia, explains Tan, so genetic sequencing could prove useful in these patients. Besides detecting the bacterium’s genetic material, sequencing can also provide information about its virulence and resistance to antibiotics, influencing treatment decisions and clinical outcomes, Tan says.

“It is essential to validate our findings in additional cohorts of intestinal metaplasia patients, preferably those that represent independent populations from different countries,” says Yeoh. “We are now working with several international groups to perform this validation study.”

The A*STAR-affiliated researchers contributing to this research are from the Biomedical Research Council, Genome Institute of Singapore, and Institute of Medical Biology.

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Huang, K. K., Ramnarayanan, K., Zhu, F., Srivastava, S., Xu, C. et al. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell 33, 137–150.e5 (2018). | Article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature