MDR1 C3435T polymorphism has no influence on developing Helicobacter pylori infection-related gastric cancer and peptic ulcer in Japanese.
OBJECTIVE
P-glycoprotein, the gene product of multidrug-resistant transporter-1 (MDR1), confers multidrug resistance against antineoplastic agents but also affects the kinetic disposition of some drugs and carcinogens. MDR1 C3435T polymorphism influences the development of colon cancer and adult acute myeloid leukemia by the association with transporting carcinogen. The aim of this study was to clarify the association of MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcers in patients with Japanese H. pylori infection.


METHODS
We assessed the MDR1 C3435T polymorphism in H. pylori-positive gastritis alone patients (n=150), gastric cancer (n=292), gastric ulcer (n=215), and duodenal ulcer (n=163) and H. pylori-negative subjects (n=168) as control by a PCR-based method.


RESULTS
No significant difference existed in frequencies of MDR1 C3435T polymorphisms between H. pylori-negative controls and H. pylori-positive gastritis alone patients. Moreover, MDR1-3435 T allele carriage didn't affect the risk of gastric cancer or peptic ulcer development. The age- and sex-adjusted odds ratios (ORs) of MDR1 3435 T allele carriers relative to the C/C genotype group for gastric cancer, gastric ulcer and duodenal ulcer risk were 0.96 (95%CI: 0.56-1.66), 1.16 (95%CI: 0.72-1.84) and 1.00 (95%CI: 0.61-1.62), respectively.


CONCLUSIONS
In this preliminary data, the association with MDR1 C3435T polymorphism and risk for developing H. pylori-related gastric cancer and peptic ulcer in Japanese was low. P-glycoprotein might not be involved in the carcinogenesis of H. pylori-related gastric cancer.
Sugimoto
Mitsushige
M
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. sugimoto@bcm.edu
Furuta
Takahisa
T
Shirai
Naohito
N
Kodaira
Chise
C
Nishino
Masafumi
M
Yamade
Mihoko
M
Ikuma
Mutsuhiro
M
Sugimura
Haruhiko
H
Ishizaki
Takashi
T
Hishida
Akira
A
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D000483:Alleles; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000235:genetics* / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1