Huge study finds strong links between 11 gene variants, gastric cancer

By Anne Harding

NEW YORK (Reuters Health) - A new meta-analysis including more than 2.5 million people has identified 11 gene variants strongly associated with gastric cancer risk.

The researchers have posted their findings online, and plan to update them annually "to create a continuously updated databank dedicated to the genetic basis of this disease, a long-standing gap in the initiatives of the international scientific community," Dr. Simone Mocellin of the University of Padova in Italy and her colleagues say. They reported their findings online March 2 in Gut.

Similar investigations have been done in breast cancer, colorectal cancer, and cutaneous melanoma, but the current study is the first to look at gastric cancer, Dr. Mocellin told Reuters Health by email.

Many polymorphisms have been linked to gastric cancer risk, Dr. Mocellin and her team note, but to date there has been no systematic review on this topic. To address the gap in knowledge, the researchers reviewed 824 studies including 2,530,706 patients and 2,841 gene variants.

They performed 456 analyses looking at 156 variants of 101 genes, identifying 11 variants in 10 genes for which there was a high level of summary evidence for a link with gastric cancer susceptibility.

Dr. Mocellin and her colleagues also found associations between polymorphisms and specific ancestral subgroups (Asian or Caucasian), tumor types (intestinal or diffuse) and tumor sites (cardia versus non-cardia).

An analysis of gene function in the 49 variants with a statistically significant gastric cancer link found 36% were involved with immunity/inflammation, 20% with apoptosis/proliferation, and 14% with adhesion/invasiveness. Sixteen of the 49 genes are located on chromosome 1, and nine are located in a region of the gene that has been tied to several other cancer types.

"The genetic basis of gastric cancer susceptibility is being elucidated," Dr. Mocellin said. "There is strong evidence linking some variants of the human genome to the development of this deadly disease. For many variants the evidence is still scarce or absent: therefore, more work is needed to define a 'genetic signature' (in the form of a test) which allows (us) to identify subjects with high risk of developing gastric cancer."

Dr. Mocellin told Reuters Health she and her team are now planning a comprehensive analysis of gene variants and lung cancer, "the most dangerous among 'big killers.'"

SOURCE: http://bit.ly/1FYeUdm

Gut 2015.

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