Title |
A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk
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Published in |
BMC Biology, August 2018
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DOI | 10.1186/s12915-018-0550-3 |
Pubmed ID | |
Authors |
Elvire Berthenet, Koji Yahara, Kaisa Thorell, Ben Pascoe, Guillaume Meric, Jane M. Mikhail, Lars Engstrand, Helena Enroth, Alain Burette, Francis Megraud, Christine Varon, John C Atherton, Sinead Smith, Thomas S. Wilkinson, Matthew D. Hitchings, Daniel Falush, Samuel K. Sheppard |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 9 | 26% |
United States | 3 | 9% |
Canada | 2 | 6% |
Australia | 1 | 3% |
South Africa | 1 | 3% |
New Zealand | 1 | 3% |
Peru | 1 | 3% |
Germany | 1 | 3% |
Chile | 1 | 3% |
Other | 1 | 3% |
Unknown | 14 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 19 | 54% |
Members of the public | 13 | 37% |
Science communicators (journalists, bloggers, editors) | 2 | 6% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 103 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 23 | 22% |
Researcher | 15 | 15% |
Student > Bachelor | 12 | 12% |
Student > Master | 7 | 7% |
Student > Doctoral Student | 6 | 6% |
Other | 13 | 13% |
Unknown | 27 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 27 | 26% |
Immunology and Microbiology | 16 | 16% |
Agricultural and Biological Sciences | 12 | 12% |
Medicine and Dentistry | 7 | 7% |
Nursing and Health Professions | 2 | 2% |
Other | 6 | 6% |
Unknown | 33 | 32% |