Interaction between GSTP1 Val allele and H. pylori infection, smoking and alcohol consumption and risk of gastric cancer among the Chinese population.
Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinese population. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790-6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475-5.521; OR = 1.638; 95% CI = 1.044-2.571; OR = 1.641; 95% CI = 0.983-2.739, respectively) (p<0.05). The GSTP1 Val allele shows an interaction with smoking, alcohol consumption, and especially H. pylori infection for increasing the risk of gastric cancer. These findings could demonstrate new pathophysiological pathways for the development of gastric cancer.
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Control in Liaoning Province, Shenyang, China.
Ye
Y
Zhang
Li-Ping
LP
Sun
Cheng-Zhong
CZ
Xing
Qian
Q
Xu
Cai-Yun
CY
He
Ping
P
Li
Yue-Hua
YH
Gong
Yun-Peng
YP
Liu
Yuan
Y
Yuan
D000428:Alcohol Drinking / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005753:Gastric Mucosa / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D016481:Helicobacter Infections / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013270:Stomach / Q000382:microbiology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D014633:Valine / Q000235:genetics
D051549:Glutathione S-Transferase pi; D014633:Valine