Polymorphism in the CagA EPIYA motif impacts development of gastric cancer.
Helicobacter pylori causes diseases ranging from gastritis to peptic ulcer disease to gastric cancer. Geographically, areas with high incidences of H. pylori infection often overlap with areas with high incidences of gastric cancer, which remains one of the leading causes of cancer-related deaths worldwide. Strains of H. pylori that carry the virulence factor cytotoxin-associated gene A (cagA) are much more likely to be associated with the development of gastric cancer. Moreover, particular C-terminal polymorphisms in CagA vary by geography and have been suggested to influence disease development. We conducted a large-scale molecular epidemiologic analysis of South Korean strains and herein report a statistical link between the East Asian CagA EPIYA-ABD genotype and the development of gastric cancer. Characterization of a subset of the Korean isolates showed that all strains from cancer patients expressed and delivered phosphorylatable CagA to host cells, whereas the presence of the cagA gene did not strictly correlate to expression and delivery of CagA in all noncancer strains.
Jones
Kathleen R
KR
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Marylan 20814, USA.
Joo
Young Min
YM
Jang
Sungil
S
Yoo
Yun-Jung
YJ
Lee
Hak Sung
HS
Chung
In-Sik
IS
Olsen
Cara H
CH
Whitmire
Jeannette M
JM
Merrell
D Scott
DS
Cha
Jeong-Heon
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics*; D005260:Female; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000382:microbiology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C080866:cagA protein, Helicobacter pylori