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Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers.

ABSTRACT: BACKGROUND:Populations in north central China are at high risk for oesophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), and genetic variation in epigenetic machinery genes and pathways may contribute to this risk. METHODS:We used the adaptive multilocus joint test to analyse 192 epigenetic genes involved in chromatin remodelling, DNA methylation and microRNA biosynthesis in 1942 ESCC and 1758 GC cases [1126 cardia (GCA) and 632 non-cardia adenocarcinoma (GNCA)] and 2111 controls with Chinese ancestry. We examined potential function of risk alleles using in silico and expression quantitative trait loci (eQTLs) analyses. RESULTS:Suggestive pathway-based associations were observed for the overall epigenetic (P-value(PATH)?=?0.034) and chromatin remodelling (P-value(PATH)?=?0.039) pathways with risk of GCA, but not GC, GNCA or ESCC. Overall, 37 different epigenetic machinery genes were associated with risk of one or more upper gastrointestinal (UGI) cancer sites (P-value(GENE?)

SUBMITTER: Sung H

PROVIDER: S-EPMC4598798 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers.

Sung Hyuna H Yang Howard H HH Zhang Han H Yang Qi Q Hu Nan N Tang Ze-Zhong ZZ Su Hua H Wang Lemin L Wang Chaoyu C Ding Ti T Fan Jin-Hu JH Qiao You-Lin YL Wheeler William W Giffen Carol C Burdett Laurie L Wang Zhaoming Z Lee Maxwell P MP Chanock Stephen J SJ Dawsey Sanford M SM Freedman Neal D ND Abnet Christian C CC Goldstein Alisa M AM Yu Kai K Taylor Philip R PR Hyland Paula L PL

International journal of epidemiology 20150427 4

<h4>Background</h4>Populations in north central China are at high risk for oesophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), and genetic variation in epigenetic machinery genes and pathways may contribute to this risk.<h4>Methods</h4>We used the adaptive multilocus joint test to analyse 192 epigenetic genes involved in chromatin remodelling, DNA methylation and microRNA biosynthesis in 1942 ESCC and 1758 GC cases [1126 cardia (GCA) and 632 non-cardia adenocarcinoma (GNCA)] and ...[more]

PMID: 25921222

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Project description:Objective: To assess the association between PTGS1 and NOS3 variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease. Methods: A case-control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Case: Patients with UGIB diagnosis. Control: Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in PTGS1 and NOS3 genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, Helicobacter pylori serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the PTSG1 gene (rs1330344, rs3842787, rs10306114, and rs5788) and NOS3 gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. Helicobacter pylori serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from Hardy-Weinberg equilibrium were verified. Results: 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13-5.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14-5.59) were associated with an increased risk for the UGIB development. In nonsteroidal anti-inflammatory drugs (NSAIDs) users, the six variants evaluated modified the magnitude of the risk of UGIB, whereas in low-dose aspirin (LDA) users, an increased risk of UGIB was observed for four of them (rs1330344, rs10306114, rs2070744, and rs1799983). Personal ulcer history (p-value: < 0.001); Helicobacter pylori infection (p-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (p-value: < 0.001); and alcohol intake (p-value: < 0.001) were also identified as independent risk factors for UGIB. Conclusion: This study presents two unprecedented analyses within the scope of the UGIB (rs10306114 and rs2070744), and our findings showing an increased risk of UGIB in the presence of the genetic variants rs10306114 and rs5788, regardless of the drug exposure. Besides, the presence of the evaluated variants might modify the magnitude of the risk of UGIB in LDA/NSAIDs users. Therefore, our data suggest the need for a personalized therapy and drug use monitoring in order to promote patient safety.

Dataset Information

Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers.

Publications

Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers.

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