			Home About us Contact

Gastric Cancer Susceptibility (gastric + cancer_susceptibility)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
Francesco Graziano
Abstract We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48,4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52,5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention. © 2005 Wiley-Liss, Inc. [source]

A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population,

MOLECULAR CARCINOGENESIS, Issue 10 2010
Jianjian Chen
Abstract Interleukin-23 receptor (IL-23R) is a key element in T helper (Th)17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case,control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR),=,0.78, 95% confidence interval (CI),=,0.68,0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR,=,0.75, 95% CI,=,0.65,0.87) other than in diffuse-type gastric cancer (adjusted allelic OR,=,0.96, 95% CI,=,0.76,1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population. © 2010 Wiley-Liss, Inc. [source]

SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility

CANCER, Issue 18 2010
Hyoungseok Ju PhD
Abstract BACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinal-type gastric cancer. The minor allele-carrying genotypes C/T and T/T had 1.6-fold greater odds of DGC than the C/C genotype (P = .00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11_17), a deletion (del) variation c.1162+664_1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls. The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P = .025). In contrast, DGC susceptibility was not associated with the c.,1969_,1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression. Cancer 2010. © 2010 American Cancer Society. [source]