Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - PreventStoCan (Understanding microbe-induced stomach cancer – the key to a workable strategy for worldwide prevention)

Teaser

Stomach cancer is the 4th most common cancer and 2nd leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is the single most important risk factor for stomach cancer. Although theoretically population-based widespread eradication of the bacterium can...

Summary

Stomach cancer is the 4th most common cancer and 2nd leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is the single most important risk factor for stomach cancer. Although theoretically population-based widespread eradication of the bacterium can reduce stomach cancer incidence and mortality, the concerns of inducing multidrug resistance problems and iatrogenic diseases related to Helicobacter pylori eradication, have hampered the implementation of this approach. We aim to develop a cost-effective and safe program for stomach cancer prevention through identification of high-risk groups, on which chemoprevention or endoscopic screening can be targeted.

Work performed

We further explored modifiers of the stomach precancerous lesion progression using the Swedish Stomach Biopsy Cohort. We found that the precancerous mucosal abnormalities recorded in a person’s first-degree relatives may improve stomach cancer risk stratification for this person. We also examined whether long-term use of proton pump inhibitors might increase stomach cancer. Our results did not support previous allegation that proton pump inhibitor treatment increases the risk of stomach cancer, irrespective of types of stomach lesions at baseline.
We have also developed a loop-mediated isothermal amplification assay for detection of Helicobacter pylori, without requirement of specific equipment. Our results showed good sensitivity and specificity, and the assay can be used without DNA extraction step. The next steps include validation of this assay using clinical samples, and extension of the capability of the assay to detect targeted Helicobacter pylori genomic mutations.
As of August 2018, all applications to 24 regional or hospital biobanks have been approved, and we are now able to request the study samples from pathological departments. So far, all machinery have been purchased (MiSeq, microtome, Laser-assisted microdissection machine) and available in our locales. A pilot study is ongoing, since some pathological departments want to perform sectioning in their own department. This is important to ensure that the sectioning of tissue blocks can be performed in a sterile and correct manner at the pathology departments. Meanwhile we also worked to optimize laboratory protocols. We will expedite collection of tissue blocks from pathology departments, and launch the study in full scale since March of 2019.

Final results

Our project takes advantage of unique setting in Sweden for epidemiological studies. In combination with the development of modern molecular biological techniques, our results will hopefully deepen the understanding of the mechanisms involved in microbe-induced gastric carcinogenesis, which will facilitate risk stratification for the identification of high-risk groups, and open up opportunities for targeted pharmacological or probiotic prevention. Eventually it will contribute significantly to the development of a workable strategy for reducing the worldwide disease burden of stomach cancer.