Abstract
BackgroundRecent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls.Methodology/Principal FindingsWe determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14–1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05–1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P trend = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05).Conclusions/SignificancesOur results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.
Highlights
Gastric cancer is one of the leading causes of cancer-related deaths in the world, accounting for 8% of the total new cases and 10% of total deaths worldwide in 2008 [1]
Extensive epidemiological studies have demonstrated that genetic variants, single nucleotide polymorphisms (SNPs), are likely to modulate the effect of environmental risk factors through modifying functions of various biological pathways involved in gastric carcinogenesis in response to environmental exposure
A significantly increased risk of gastric cancer was associated with variant genotypes (AG+GG) of rs2274223 with an adjusted odds ratios (ORs) of 1.35 and (CG+CC) of rs11187870 with an adjusted OR of 1.26, compared with the wild-type homozygous genotypes, respectively
Summary
Gastric cancer is one of the leading causes of cancer-related deaths in the world, accounting for 8% of the total new cases and 10% of total deaths worldwide in 2008 [1]. Established environmental factors associated with risk of gastric cancer include Helicobacter pylori infection [5], dietary habits (e.g., high intake of salt-preserved and nitrated foods), smoking, pernicious anemia and a history of partial gastrectomy [6]. Extensive epidemiological studies have demonstrated that genetic variants, single nucleotide polymorphisms (SNPs), are likely to modulate the effect of environmental risk factors through modifying functions of various biological pathways involved in gastric carcinogenesis in response to environmental exposure. Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A.G) in PLCE1 to be associated with risk of gastric adenocarcinoma. We validated this finding and explored the risk associated with another unreported potentially functional SNP (rs11187870 G.C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls
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