Brief Article
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World J Gastroenterol. Jun 21, 2013; 19(23): 3615-3622
Published online Jun 21, 2013. doi: 10.3748/wjg.v19.i23.3615
Gastric precancerous lesions are associated with gene variants in Helicobacter pylori-susceptible ethnic Malays
Sathiya Maran, Yeong Yeh Lee, Shuhua Xu, Nur-Shafawati Rajab, Norhazrini Hasan, Syed Hassan Syed Abdul Aziz, Noorizan Abdul Majid, Bin Alwi Zilfalil
Sathiya Maran, Nur-Shafawati Rajab, Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia
Yeong Yeh Lee, Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia
Shuhua Xu, Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China
Norhazrini Hasan, Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia
Syed Hassan Syed Abdul Aziz, Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia
Noorizan Abdul Majid, Bin Alwi Zilfalil, Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia
Author contributions: Maran S, Lee YY, Xu S, Majid NA and Zilfalil BA were involved in the design, analysis and writing of manuscript; Maran S performed the studies, with assistance from Rajab NS and Hasan N; Syed Abdul Aziz SH, Rajab N and Hasan N provided ideas to the study and manuscript.
Supported by Fundamental Research Grant Scheme (FRGS) 203/PPSP/6171121, 1001/PPSP/812016 and 1001/PPSP/8122022 of Universiti Sains Malaysia; The National Science Foundation of China grants, No. 30971577 and No. 31171218; the Shanghai Rising-Star Program, No. 11QA1407600; and the Science Foundation of the Chinese Academy of Sciences (CAS) (KSCX2-EW-Q-1-11; KSCX2-EW-R-01-05; KSCX2-EW-J-15-05)
Correspondence to: Yeong Yeh Lee, MD, FRCP, FACP, Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kota Bahru, Malaysia. justnleeyy@gmail.com
Telephone: +60-9-7663448 Fax: +60-9-7648277
Received: February 18, 2013
Revised: April 2, 2013
Accepted: April 9, 2013
Published online: June 21, 2013
Processing time: 121 Days and 18.5 Hours
Abstract

AIM: To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.

METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as “cases”. Thirty-seven Malay subjects who were H. pylori negative and had no precancerous lesions were included as “controls”. Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers.

RESULTS: Of the 23 H. pylori-positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori-positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in “cases”vs“controls” for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively.

CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.

Keywords: Gastric precancerous lesions; Gene polymorphisms; Genome-wide association; Helicobacter pylori; Malays

Core tip: Gastric cancer and its precancerous lesions are exceptionally rare among ethnic Malays. Gene variants may be associated with precancerous lesions in Helicobacter pylori-susceptible Malays. Genome-wide association was performed to identify gene variants in Malays with a spectrum of gastric precancerous lesions. Results indicated that at different phases of the Correa cascade, different gene variants were manifest, but they followed a pattern of progression similar to their histological and clinical stages. It is possible that, in addition to histological staging, gene variant markers may serve to identify different phases of gastric cancer progression in the near future.