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)