Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.

Loh JT, Shaffer CL, Piazuelo MB, Bravo LE, McClain MS, Correa P, Cover TL
Cancer Epidemiol Biomarkers Prev. 2011 20 (10): 2237-49

PMID: 21859954 · PMCID: PMC3189306 · DOI:10.1158/1055-9965.EPI-11-0548

BACKGROUND - Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis.

METHODS - We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain.

RESULTS - A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif.

CONCLUSIONS - CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk.

IMPACT - These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not.

©2011 AACR

MeSH Terms (27)

Adult Antigens, Bacterial Bacterial Proteins Biomarkers, Tumor Biopsy Blotting, Western Case-Control Studies Cohort Studies Colombia DNA, Bacterial Female Follow-Up Studies Gastric Mucosa Helicobacter Infections Helicobacter pylori Humans Male Middle Aged Mutagenesis Nucleotide Motifs Precancerous Conditions Prognosis Promoter Regions, Genetic Real-Time Polymerase Chain Reaction Risk Factors Stomach Stomach Neoplasms

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