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• W2070087162 abstract "We read with interest the article entitled “A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer” by Rhead et al1Rhead J.L. Letley D.P. Mohammadi M. et al.A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer.Gastroenterology. 2007; 133: 926-936Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar in the September 2007 issue of Gastroenterology. Virtually all Helicobacter pylori strains possess a vacuolating cytotoxin gene, vacA; however, there is considerable variation in vacuolating activities among strains, and this variation is primarily due to differences in vacA gene structure at the signal region (s1 and s2) and the midregion (m1 and m2).2Atherton J.C. Cao P. Peek Jr, R.M. et al.Mosaicism in vacuolating cytotoxin alleles of Helicobacter pyloriAssociation of specific vacA types with cytotoxin production and peptic ulceration.J Biol Chem. 1995; 270: 17771-17777Crossref PubMed Scopus (1363) Google Scholar Rhead et al1Rhead J.L. Letley D.P. Mohammadi M. et al.A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer.Gastroenterology. 2007; 133: 926-936Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar identified a third polymorphic determinant of vacuolating activity, located between the signal region and midregion, which they termed the intermediate (i) region. Two i-region types were identified, i1 and i2; the authors reported that i1-type strains were strongly associated with gastric adenocarcinoma in Iranian patients and hypothesized that vacA i-region typing may provide an improved predictor of H pylori strain carcinogenic potential. It has been proposed that H pylori virulence factor should (1) have a disease or other in vivo correlation, (2) have epidemiologic consistency across populations and regions, (3) be a biologic plausibility, and (4) the effect should be reduced or eliminated by gene deletion and be restored by complementation.3Lu H. Yamaoka Y. Graham D.Y. Helicobacter pylori virulence factors: facts and fantasies.Curr Opin Gastroenterol. 2005; 21: 653-659Crossref PubMed Scopus (100) Google Scholar Most false leads have resulted from studying strains from only 1 region. We therefore examined vacA i region in 314 strains isolated from East Asian and Southeast Asian countries from patients with nonulcer dyspepsia, gastric ulcers, duodenal ulcers, or gastric cancer. As expected, all strains studied were vacA s1 genotype. In agreement with the report by Rhead et al, 98% of s1—m1 strains (96% of total) were i1; 5 strains were i1 and i2 mixed genotype (Table 1). Only 8% (4 of 52) s1—m2 strains were i2 genotype and there was no disease association between genotype and outcome. This is in contrast to Rhead et al,1Rhead J.L. Letley D.P. Mohammadi M. et al.A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer.Gastroenterology. 2007; 133: 926-936Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar where 55% of Western s1—m2 strains from the United States and United Kingdom and 54% of Iranian s1—m2 strains were i2 genotype. It has previously been shown that vacA s and m genotypes are also not useful as disease determinant markers in East Asian and Southeast Asian populations.4Vilaichone R.K. Mahachai V. Tumwasorn S. et al.Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads.Helicobacter. 2004; 9: 453-459Crossref PubMed Scopus (77) Google Scholar, 5Yamaoka Y. Kodama T. Kita M. et al.Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome.Helicobacter. 1998; 3: 241-253Crossref PubMed Scopus (153) Google Scholar, 6Yamaoka Y. Kodama T. Gutierrez O. et al.Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries.J Clin Microbiol. 1999; 37: 2274-2279PubMed Google Scholar, 7Yamaoka Y. Souchek J. Odenbreit S. et al.Discrimination between cases of duodenal ulcer and gastritis on the basis of putative virulence factors of Helicobacter pylori.J Clin Microbiol. 2002; 40: 2244-2246Crossref PubMed Scopus (82) Google Scholar We can conclude that vacA genotypes with combination of 3 regions also failed as a disease determinant in the East Asian and Southeast Asian countries where gastric cancer is a major clinical problem.Table 1Relationship Between vacA i–m Regions and Clinical Outcomes in East and Southeast AsiaDiseaseni1—m1 (%)i1—m2 (%)i2—m2 (%)(i1+i2)—m1 (%)(i1+i2)—m2 (%)i1—(m1+m2) (%)GC81841401.21.20DU5476175.601.90GU6085121.71.700NUD118811502.50.80.8Total31381141.31.61.00.3GC, gastric cancer; DU, duodenal ulcer; GU, gastric ulcer; NUD, nonulcer dyspepsia. Open table in a new tab GC, gastric cancer; DU, duodenal ulcer; GU, gastric ulcer; NUD, nonulcer dyspepsia. ReplyGastroenterologyVol. 134Issue 4PreviewThank you for the opportunity to reply to the comments of Ogiwara, Graham, and Yamaoka regarding our recent publication in Gastroenterology.1 We were very interested to read their data on vacA i-region typing of 314 Helicobacter pylori strains isolated from East Asian and Southeast Asian countries, and see no conflict between their findings and the conclusions we have drawn from our own data.1 In a recent abstract, we described the i-region types of 13 vacA s1/m2 strains isolated in China, which we also found to be invariably i1 type. Full-Text PDF" @default.
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