Differences in amino acid frequency in CagA and VacA sequences ofHelicobacter pyloridistinguish gastric cancer from gastric MALT lymphoma.
BACKGROUND
Helicobacter pyloriis a pathogenic bacterium that causes various gastrointestinal diseases. The most common gastric malignancies associated withH. pyloriare gastric cancer and lymphoma of mucosa associated lymphoid tissue (MALT).Helicobacter pylorivirulence genes, namelycagAandvacA,are known to be associated with malignancy development. Conventionally,cagAandvacAwere classified by looking at partial sequences of the genes. However, such genotyping has hardly proven useful predicting different risks for gastric cancer or MALT lymphoma. In search of new loci that distinguish these diseases, we investigated the full sequences ofcagAandvacA.


RESULTS
We comparedcagAandvacAsequences of 18 and 12H. pyloristrains obtained, respectively, from patients with gastric cancer and MALT lymphoma in Oita, Japan. Conventional genotyping ofcagAandvacAshowed no significant difference between the two diseases. We further investigated the full protein sequences of CagA and VacA to identify loci where allele frequency was significantly different between the diseases. We found four such loci on CagA, and three such loci on VacA. We also inspected the corresponding loci on the genes of 22 gastritis strains that potentially lead to gastric cancer or MALT lymphoma in the long run. Significant differences were observed at one CagA locus between gastritis and MALT lymphoma strains, and at one VacA locus between gastritis and gastric cancer strains.


CONCLUSIONS
We found novel candidate loci inH. pylorivirulence genes in association with two different types of gastric malignancies that could not be differentiated by conventional genotyping. Biological connotations of the amino acid polymorphisms merit further study.
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan ; Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Masahiko
M
Hashinaga
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Rumiko
R
Suzuki
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Junko
J
Akada
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Takashi
T
Matsumoto
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Yasutoshi
Y
Kido
Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Tadayoshi
T
Okimoto
Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan ; Faculty of Welfare and Health Science, Oita University, 700 Dannoharu, Oita, Oita 870-1192 Japan.
Masaaki
M
Kodama
Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.
Kazunari
K
Murakami
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan ; Department of Medicine-Gastroenterology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX USA.
Yoshio
Y
Yamaoka
Amino acid polymorphism; Helicobacter pylori; Next generation sequencing; cagA; vacA