The bacterium Helicobacter pylori is bad news for the stomach — in particular because it is responsible for at least half of all gastric cancers. But how H. pylori causes cancer is not clear. In their recent paper, Maekita and colleagues explore the association between H. pylori and aberrant DNA methylation in the gastric mucosa.

The researchers measured the levels of DNA methylation at certain CpG islands of individuals who were, or who were not, infected with H. pylori. CpG islands are often aberrantly methylated in cancers, and in gastric cancer cells, tumour suppressors (specifically, INK4a (also known as cyclin-dependent-kinase-inhibitor 2A, or p16), CDH1 (also known as E-cadherin) and MLH1) are inactivated by DNA methylation more often than they are through mutation.

Maekita and colleagues used methylation-specific PCR to determine levels of methylation in eight regions of the genome — two regions in a CpG island associated with INK4a and six regions in CpG islands associated with LOX (lysyl oxidase, which is also a tumour suppressor), HRAS-like suppressor and THBD (both of which are putative tumour suppressors), and p41ARC (also known as actin-related protein 2/3 complex, subunit 1B), HAND1 and FLNC (which are frequently methylated in gastric cancers).

They found that individuals who were infected with H. pylori (but who did not have gastric cancer) had high levels of abnormal methylation at all eight CpG islands. The same CpG islands were also aberrantly methylated in patients with gastric cancer (but no existing H. pylori infection). From this, the authors suggest that H. pylori might increase the risk of cancer by inducing aberrant methylation in the gastric mucosa, and they discuss possible mechanisms for this. Previous studies indicate that de novo DNA methylation can be induced by cell proliferation, which is a feature of H. pylori infection. The researchers also speculate that the strong, chronic inflammation could be responsible. Whatever the mechanism, these findings indicate that measuring levels of methylation at specific CpG islands could be used as a mechanism of risk assessment for gastric cancer.