Published online Jun 21, 2013. doi: 10.3748/wjg.v19.i23.3615
Revised: April 2, 2013
Accepted: April 9, 2013
Published online: June 21, 2013
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.
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.