Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa.
Infection by Helicobacter pylori is the most important risk factor for gastric cancer. However, only a small fraction of colonized individuals, representing at least half of the world's population, develop this malignancy. In order to shed light on host-microbial interactions, gastric mucosa biopsies were collected from 119 patients suffering from dyspeptic symptoms. 8-Hydroxy-2'-deoxyguanosine (8-oxo-dG) levels in the gastric mucosa were increased in carriers of H.pylori, detected either by cultural method or by polymerase chain reaction, and were further increased in subjects infected with strains positive for the cagA gene, encoding the cytotoxin-associated protein, cagA. Oxidative DNA damage was more pronounced in males, in older subjects, and in H.pylori-positive subjects suffering from gastric dysplasia. Moreover, 8-oxo-dG levels were significantly higher in a small subset of subjects having a homozygous variant allele of the 8-oxoguanosine-glycosylase 1 (OGG1) gene, encoding the enzyme removing 8-oxo-dG from DNA. Conversely, they were not significantly elevated in glutathione S-transferase M1 (GSTM1)-null subjects. Thus, both bacterial and host gene polymorphisms affect oxidative stress and DNA damage, which is believed to represent a key mechanism in the pathogenesis of gastric cancer. The interplay between bacterial and host gene polymorphisms may explain why gastric cancer only occurs in a small fraction of H.pylori-infected individuals.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132, Genoa, Italy.
De Flora
Silvio
S
Cartiglia
Cristina
C
Are
Bianca Maria
BM
Longobardi
Mariagrazia
M
Camoirano
Anna
A
Mura
Ida
I
Dore
Maria Pina
MP
Scanu
Antonio Mario
AM
Rocca
Paolo Cossu
PC
Maida
Alessandro
A
Piana
Andrea
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004415:Dyspepsia / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000821:virology
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D045647:DNA Glycosylases; D004279:DNA, Viral; D003849:Deoxyguanosine; D005982:Glutathione Transferase; D017382:Reactive Oxygen Species; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; C479058:oxoguanine glycosylase 1, human