Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New clues on the link between Heliobacter pylori and stomach cancer

08.05.2009
Heliobacter pylori (H. pylori) infection is considered one of the most important risk factors for stomach (or gastric) cancer with as much as 65% of all cases linked back to the bacteria, although exactly how this occurs is not fully clear.

But now researchers in Denmark, Portugal and France, publishing in the journal Clinical Cancer Research1, show that H. pylori infection contribution to cancer can be linked to at least three independent molecular pathways, which, when disturbed by infection, lead to mutations in the patients’ gastric tissues.

Interestingly, this accumulation of mutations occur only during the initial stages of infection making intervention at this stage crucial if to prevent cancer, a particularly important information when deciding more efficient medical approaches in those areas where antibiotic resistance and re-infection is so widespread that question the relevance of giving treatment against infection.

Despite a drastic reduction in the number of cases, stomach cancer is still the 4th most common cancer and the 2nd cause of cancer death in the world, with about 1 million of people dying every year. That, only in the UK, around 8.000 new cases are diagnosed per year is enough to reveal the magnitude of the problem. The best established risk factor for stomach cancer is Helicobacter pylori infection with a capability to double the risk of disease, although the more virulent H. pylori strains can push this number to as much as 30-fold. This is believed to occur because of the bacteria capacity to lead to acute gastritis, which, if not treated, can becomes chronic and, with time, evolve to more serious disturbances of the gastric wall as result of the chronic inflammation produced by the infection.

Still, although more than half of the world population is infected with H. pylori only a small percentage of these individuals goes to develop cancer proving that other factors are also important. These are known to include the environment – diet and smoking for example – as well as the host genetic predisposition such as a pro-inflammatory genetic profile. But despite these well recognised associations the exact molecular mechanisms behind gastric cancer development – particularly those linked to H. pylori infection – are far from being understood

In this new study researchers Ana Machado, Ceu Figueiredo and Raquel Seruca at IPATIMUP, Eliette Touati from Institute Pasteur and Lene Rasmussen from Roskilde University in Denmark do a through investigation into the problem with the help of three parallel models: human gastric cells growing in laboratory and mice, both infected with a very virulent H. pylori, and cells from biopsies of infected patients with chronic gastritis – trying to understand exactly what happens in H. pylori infected stomachs.

Previous studies have suggested that one of cell systems affected by H. pylori infection was the DNA repair mechanism, mismatch repair (MMR), which – like the name indicates – identifies mismatched pieces of DNA and calls for proteins that cut and insert properly complementary ones. And in fact when Machado, Figueiredo and colleagues looked at H. pylori infected cells their, MMR levels were abnormally reduced, an observation further confirmed in gastric cells of infected mice, although, interestingly, only at 3 months post-infection as normal levels were already restored after 12 months (when the chronic disease is already chronic).

Because problems in MMR are known to result in genomic instability and mutations, the stomachs of infected mice were analysed after 6 months of infection to find, that in fact, they contained an abnormal number of mutations although, again, by 12 months post-infection values were back to normal, in agreement with previously observed MMR variations.

What these results suggested was that H. pylori effect on MMR was temporary, and that by 12 months, when MMR is back to normal and no more mutations are accumulating, the altered cells have also been eliminated probably by a compensatory mechanism such as accelerated cell death and fast cell division. Nevertheless, as we know that one escaped cell at this stage, later progressing to malignancy, is enough to induce cancer this observation of apparent normality at 12 months does not exclude the possibility of cancer appearance later on.

Mutations in mitochondrial DNA (mitochondrion are the cell’s power plants supplying energy for all its functions) have been found in pre-cancerous gastric cells. Not only that but it has been suggested that H. pylori could lead to oxidative stress - a situation where highly reactive oxygen molecules, which are normally the by-product of mitochondria, occur in toxic quantities damaging the DNA. Both these observations suggested that mitochondria’s function could be affected during H. pylori infection and led Machado and Figueiredo to investigate.

And in fact, when the researchers looked into the infected cells’ mitochondrial DNA this again presented abnormally high number of mutations. The relevance of this observation was confirmed when gastric cells from infected patients with chronic gastritis where found to have, not only an abnormal number of mutations, but mutations of the same type and affecting the same areas in the mitochondrial DNA, than those found in the infected cells. Further confirming that these mutations were linked to the H. pylori infection, the more virulent was the strain infecting the patient, the higher was the number of mutations found in their gastric cells. The researchers also found that BER – a DNA repair mechanism linked to oxidative damage in mitochondrial DNA – was also affected during the infection with one of its components not being produced in quantities enough to allow proper DNA repair.

Machado, Figueiredo and colleagues’ work reveal that H. pylori infection seems to affect temporarily the host DNA repair mechanisms resulting in a dangerous accumulation of mutations. These mutations, although apparently eliminated when the infection is chronic, have, nevertheless, the potential to originate cancer as one escaped malignant cell is enough to trigger the whole process. In conclusion, H. pylori-induced carcinogenesis is the combinatorial result of at least three linked mutagenic phenomena resulting from impairments in MMR, mitochondria and BER.

This work has several implications: for a start it helps to establish a definitive link between H. pylori and cancer development, explaining (at least part of) the molecular mechanism behind it, and maybe contributing to the development of better strategies for the prevention of stomach cancer.

In fact, trials to prevent cancer by eradicating the bacteria have had conflicting results, which now might be partially explained by the fact that H. pylori infection only seems to be mutagenic during the early stages of disease, so treatment at later stages of the disease would not be effective preventing cancer. Until now consensus was that the optimum time to eradicate H. pylori was before intestinal metaplasia appeared, but even this seemed to be relevant in only a subset of subjects. On the face of Machado and Figueiredo’s study it will be interesting to see if eradication at a much earlier stage, more in agreement with the results here described, could help to substantially increase the number of those responding to treatment.

Finally, Machado and Figueiredo’s study is also particularly important in those regions where both H. pylori infection and antibiotic resistance are at rift, and where some defend that - due to the high probability of reinfection - treating the disease is not worthwhile, as it shows that, at least among those patients recently infected, treatment can be crucial to prevent cancer.

Stomach cancer is not only incredibly widespread but it also has a very poor prognosis with less than 20% of the patients -15% in the UK - surviving more than 5 years, what makes any new information on the disease with potential to help preventing it, particular important.

Piece by Catarina Amorim (catarina.amorim at linacre.ox.ac.uk)

Catarina Amorim | alfa
Further information:
http://clincancerres.aacrjournals.org/cgi/content/abstract/15/9/2995

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>