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BMC Biol. 2018 Aug 2;16(1):84. doi: 10.1186/s12915-018-0550-3.

A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk.

Author information

Microbiology and Infectious Disease Group, Swansea University Medical School, Swansea University, Swansea, UK.
Antimicrobial Resistance Research Centre, National Institute of Infectious Diseases, Toyama, Japan.
Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.
School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, CF10 3AX, UK.
Systems Biology Research Group, School of Biosciences, University of Skövde, Skövde, Sweden.
Department of Gastroenterology, Centre Hospitalier Interrégional Edith Cavell/Site de la Basilique, Brussels, USA.
Laboratoire de Bactériologie, Centre National de Référence des Campylobacters et des Hélicobacters, Place Amélie Raba Léon, 33076, Bordeaux, France.
INSERM, University Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, 33000, Bordeaux, France.
Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.
The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, UK.



Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression.


We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori, as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation.


There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.


GWAS; Gastric cancer; Helicobacter pylori

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