Myeloperoxidase G–463A polymorphism and the risk of gastric cancer: a case–control study
Advance Access publication July
Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study
Huaijun Zhu 2
Li Yang 1 2
Bo Zhou 2
Rongbin Yu 0
Naping Tang 2
Bin Wang 2
0 Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University , China
1 Department of General Surgery, First Affiliated Hospital of Nanjing Medical University
2 Key Laboratory of Reproductive Medicine, Department of Pharmacology, Nanjing Medical University , 140 Hanzhong Road, Nanjing, 210029 , China
Several epidemiological studies have shown that the myeloperoxidase (MPO) G-463A polymorphism may influence the risk of many cancers, including lung, breast, bladder and laryngeal cancer. However, there is no study concerning the MPO polymorphism and gastric cancer risk. In this hospital-based, case-control study, we used polymerase chain reaction-restriction fragment length polymorphism protocols to examine the prevalence of MPO G-463A polymorphism in gastric cancer. A significantly different distribution of the MPO -463G/A genotype was demonstrated among the cases and controls (c2 ¼ 7.42, P ¼ 0.03). Subjects with the variant genotypes (the sum of GA and AA) had a 44% reduced risk of gastric cancer relative to those with GG [adjusted odds ratio (OR) ¼ 0.56; 95% CI: 0.32-0.97]. Stratified analyses revealed that the protective effect of A allele was significant in male (adjusted OR ¼ 0.51; 95% CI: 0.260.98) or younger subjects (age <58 years) (adjusted OR ¼ 0.42; 95% CI: 0.18-0.94), but not in female or older subjects. In addition, there was also a significantly reduced risk in subjects residing in rural areas (adjusted OR ¼ 0.41; 95% CI: 0.18-0.95) but not in urban areas. The interaction between the MPO G-463A polymorphism and smoking status was not observed in this study. Tumor differentiation was also not found to be associated with the MPO genotype. In conclusion, our results showed that the MPO 463 G to A variant may be associated with the decreased risk of gastric cancer in Chinese population.
Introduction
Reported by International Agency for Research on Cancer in
2005 (Global Cancer Statistics, 2002), gastric cancer is the
fourth common cancer (934 000 cases per year, 8.6% of total
cancers) and the second most fatal malignancy worldwide
(700 000 deaths/year, 10.4% of total cancers) (
1
). Although
the incidence and mortality of gastric cancer have been
decreasing in Western countries over the past few decades,
high rates are still present in East Asia, Eastern Europe, parts
of Central and South America (
1,2
). As indicated previously
Abbreviations: GST, glutathione S-transferases; MPO, myeloperoxidase.
†The first two authors contributed equally to this work.
by us, the populations in developing countries adopt western
diets and a high-stress lifestyle, the geographic distribution of
many chronic diseases’ incidence has changed (
3–5
). And an
investigation in China including 169 871 men and women
demonstrated that gastric cancer was in the third place among
the five leading causes of death from cancer (6).
Gastric cancer has been considered to be a result of gene–
environment interactions, which is a complex multifactorial
and multistage process (
7
). Published studies have identified
that gastric cancer is associated with polymorphisms in genes
involved in inflammatory response, DNA repair, metabolic
enzymes and oxidative damage (
8
). Previous studies in
Chinese population also found that gastric cancer risk was
associated with polymorphisms in DNA repair gene XRCC1
(
9
) and 5,10-methylenetetrahydrofolate reductase (MTHFR)
(
10
). Oxidative stress has been confirmed to play important
roles in various diseases. In our previous epidemiological
studies, oxidative stress was found to be related to cataract
(
3
) and coronary artery disease (
4
). The polymorphisms of
oxidative stress-related enzymes have been detected in gastric
cancer. NAD(P)H: quinone oxidoreductase 1 (NQO1) 609
CT/TT, glutathione S-transferases (GST) T1 null genotype
and double null GST M1-GST T1 genotype were all found to
be associated with an increased gastric cancer risk (
11,12
).
However, the manganese superoxide dismutase (Mn SOD)
polymorphisms at 102 C to T and the 9 T to C were not
found to be associated with gastric cancer in a Polish case–
control study (13).
As an oxidative stress-related enzyme, myeloperoxidase
(MPO) is a lysosomal hemoprotein located in
polymorphonuclear neutrophils and monocytes. It can catalyze a reaction
that produces hypochlorous acid (HOCl), which may cause
host DNA damage and lead to the mutation of oncogenes and
tumor suppressor genes (
14,15
). Austin et al. (16) identified a
G–463A polymorphism in the promoter region of the MPO
gene among leukemia patients. It has been reported that
the A allele was associated with a significantly decreased
transcriptional activity compared with the G allele, because
of the disruption of an SP1-binding sit (...truncated)