Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis

Vinall, Lynne E.; King, M. Bruce; Novelli, Marco; Green, Carole A.; Daniels, Geoff; Hilkens, John; Sarner, M.; Swallow, Dallas M.

doi:10.1053/gast.2002.34157

Cited by 98 publications

(90 citation statements)

References 47 publications

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“…Our observations of increased susceptibility to infection by mucin-binding bacteria in Muc1 -/-mice are consistent with molecular epidemiological studies linking polymorphisms in the length of the MUC1 extracellular domain with development of gastritis and gastric cancer following infection with the mucinbinding gastric pathogen H. pylori (34)(35)(36)(37). While Muc1 -/-mice showed dramatically increased susceptibility to systemic infection by C. jejuni, no differences were demonstrated with an intestinal pathogen, S. typhimurium, that targets M cells, thereby circumventing the cell surface mucin barrier.…”

Section: Discussionsupporting

confidence: 89%

MUC1 cell surface mucin is a critical element of the mucosal barrier to infection

McAuley¹,

Lindén²,

Png³

et al. 2007

J. Clin. Invest.

370

291

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Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell surface mucins protect mucosal cells from infection. A rapid progressive increase in gastrointestinal expression of mucin 1 (Muc1) cell surface mucin followed infection of mice with the bacterial pathogen Campylobacter jejuni. In the first week following oral infection, C. jejuni was detected in the systemic organs of the vast majority of Muc1 -/-mice but never in Muc1 +/+ mice. Although C. jejuni entered gastrointestinal epithelial cells of both Muc1 -/-and Muc1 +/+ mice, small intestinal damage as manifested by increased apoptosis and enucleated and shed villous epithelium was more common in Muc1 -/-mice. Using radiation chimeras, we determined that prevention of systemic infection in wild-type mice was due exclusively to epithelial Muc1 rather than Muc1 on hematopoietic cells. Expression of MUC1-enhanced resistance to C. jejuni cytolethal distending toxin (CDT) in vitro and CDT null C. jejuni showed lower gastric colonization in Muc1 -/-mice in vivo. We believe this is the first in vivo experimental study to demonstrate that cell surface mucins are a critical component of mucosal defence and that the study provides the foundation for exploration of their contribution to epithelial infectious and inflammatory diseases.

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Section: Discussionsupporting

confidence: 89%

MUC1 cell surface mucin is a critical element of the mucosal barrier to infection

McAuley¹,

Lindén²,

Png³

et al. 2007

J. Clin. Invest.

370

291

View full text Add to dashboard Cite

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“…MUC1 is a highly polymorphic membraneassociated mucin that is often expressed aberrantly in cancer (Taylor-Papadimitriou et al, 2002). In addition, MUC1 was reported to bind to H. pylori (Lindén et al, 2004;McGuckin et al, 2007); MUC1 knockout mice are susceptible to H. pylori gastritis (McGuckin et al, 2007), and there is an altered pattern of expression of MUC1 in H. pylori gastritis (Vinall et al, 2002). Two previous studies also found genetic variations in MUC1 that were associated with GC susceptibility (Jia et al, 2010;Xu et al, 2009).…”

Section: Discussionmentioning

confidence: 95%

Association of Genetic Polymorphisms at 1q22 but not 10q23 with Gastric Cancer in a Southern Chinese Population

Yang

Li²,

Zhou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: Data from a recent genome-wide association studiesy of gastric cancer (GC) and oesophageal squamous cell carcinoma in Chinese living in the Taihang Mountains of north-central China suggest that 1q22 and 10q23 are susceptibility-associated regions for GC. However, this has not been confirmed in southern Chinese populations. The aim of this study was to investigate whether these polymorphisms at 1q22 and 10q23 are associated with the risk of GC in a southern Chinese population. Methods: We selected seven top significant associated single nucleotide polymorphisms (SNPs) at 1q22 and 10q23 and conducted a population-based casecontrol study in a southern Chinese population. Genotypes were determined using MassARRAYTM system (Sequenome, San Diego, CA). Results: Two SNPs at 1q22, rs4072037 and rs4460629, were significantly associated with a reduced risk of GC, best fitting the dominant genetic model. Logistic regression models adjusted for age and sex showed that rs4072037 AG and GG (OR=0.64, P=0.017, compared with AA) and rs4460629 CT and TT (OR=0.54, P=0.0016, compared with TT) significantly reduced the risk of GC. However, no significant results for the five SNPs at 10q23 were obtained in this study. Conclusion: These outcomes indicate that 1q22 is associated with GC susceptibility in this southern Chinese population, while an association for the locus at 10q23 was not confirmed.

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“…Thus, MUC1 is often aberrantly expressed in stomach cancer, and it is a ligand for H. pylori (Ng et al, 2008). Susceptibility to H. pylori infection and gastric cancer appears to be associated with MUC1 allele length (Costa et al, 2008;Vinall et al, 2002 (Xu et al, 2009;Jia et al, 2010;Zhang et al, 2011) with controversial results (Abnet et al, 2010;He et al, 2013). Because gastric cancer has potential genetic heterogeneity among different populations, the current study was conducted to investigate whether common polymorphisms in MUC1 gene were associated with H. pylori infection, and with non-cardia gastric cancer risk in north-western Chinese Han population.…”

Section: Introductionmentioning

confidence: 99%

Lack of Association of Common Polymorphisms in MUC1 Gene with H. pylori Infection and Non-cardia Gastric Cancer Risk in a Chinese Population

Zhang

Hao²,

Gao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Several lines of evidence support the notion that MUC1 is often aberrantly expressed in gastric cancer, and it is a ligand for Helicobacter pylori. Genetic variation in MUC1 gene may confer susceptibility to H. pylori infection and gastric cancer. We assessed the association of common polymorphisms in MUC1 gene with H. pylori infection and non-cardia gastric cancer using an LD-based tag SNP approach in north-western Chinese Han population. A total of four SNPs were successfully genotyped among 288 patients with non-cardia gastric cancer and 281 age-and sex-matched controls. None of the tested SNPs was associated with H. pylori infection. SNP rs9426886 was associated with a decreased risk of non-cardia gastric cancer, but lost significance after adjustment for multiple testing. Overall, our data indicated that common genetic variations in MUC1 gene might not make a major contribution to the risk of H. pylori infection and non-cardia gastric cancer in our studied population.

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Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis

Cited by 98 publications

References 47 publications

MUC1 cell surface mucin is a critical element of the mucosal barrier to infection

MUC1 cell surface mucin is a critical element of the mucosal barrier to infection

Association of Genetic Polymorphisms at 1q22 but not 10q23 with Gastric Cancer in a Southern Chinese Population

Lack of Association of Common Polymorphisms in MUC1 Gene with H. pylori Infection and Non-cardia Gastric Cancer Risk in a Chinese Population

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