Genetic polymorphisms of the cancer related gene and Helicobacter pylori infection in Japanese gastric cancer patients. An age and gender matched case-control study.
BACKGROUND
Gastric cancer is a multistage process, each caused by numerous factors. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiologic techniques and serum markers.


METHODS
Serum pepsinogen I levels, pepsinogen I/pepsinogen II (I/II) ratios, serum IgG antibody against Helicobacter pylori (H. pylori), and genetic polymorphisms of cytochrome p450 2E1 (CYP2E1), glutathione-S-transferase M1 (GSTM1), and L-myc protooncogenes were analyzed in 82 persons with gastric cancer and in 151 age- and sex-matched controls, who were selected from 208 gastric cancer patients and 375 noncancer patients, respectively. Statistical analysis was performed to elucidate which risk factors for gastric cancer were contributing the most to gastric carcinogenicity.


RESULTS
Serum pepsinogen I level (odds ratio [OR] = 1.81; 95% confidence interval [CI], 1.04-3.16) and pepsinogen I/II ratios (OR = 3.09; 95% CI, 1.74-5.49) were significantly associated with gastric cancer risk in a case-control study. Seropositivity of serum IgG antibody against H. pylori (OR = 1.25; 95% CI, 0.84-1.85) and specific genotypes of a L-myc genetic polymorphism (OR = 1.33; 95% CI, 0.59-2.99) were more commonly observed in gastric cancer cases, but this was not statistically significant. Specific genotypes of the CYP2E1 RsaI polymorphism and GSTM1 gene deletion were not associated with gastric cancer.


CONCLUSIONS
Atrophic mucosal change, indicated by serum pepsinogen levels, is possible a risk factor for gastric cancer. H. pylori infection and genetic polymorphisms of CYP2E1, L-myc, and GSTM1 genetic polymorphisms were not risk factors in this study.
Kato
S
S
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Onda
M
M
Matsukura
N
N
Tokunaga
A
A
Matsuda
N
N
Yamashita
K
K
Shields
P G
PG
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D001483:Base Sequence; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016259:Genes, myc; D005982:Glutathione Transferase / Q000235:genetics; D016481:Helicobacter Infections / Q000453:epidemiology* / Q000235:genetics; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D010435:Pepsinogens / Q000097:blood; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011519:Proto-Oncogenes; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D010435:Pepsinogens; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase