From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

<p>Abstract</p> <p>Background</p> <p><it>elicobacter pylori </it>infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach.</p> <p>Results</p> <p>A set of 254 <it>H. pylori </it>genes was used to perform array-based comparative genomic hybridization among 120 French <it>H. pylori </it>strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with <it>cag</it>PAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released <it>H. pylori </it>genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest <it>H. pylori </it>genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the <it>vacA</it>s2m2 allele and lacks the genes encoding the major virulence factors (absence of <it>cag</it>PAI, <it>bab</it>B, <it>bab</it>C, <it>sab</it>B, and <it>hom</it>B). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 <it>H. pylori </it>sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38.</p> <p>Conclusion</p> <p>These isolates are deprived of the main <it>H. pylori </it>virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.</p

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer