Dataset Information

Genetic variants and risk of gastric cancer: a pathway analysis of a genome-wide association study.

ABSTRACT: This study aimed to discover candidate single nucleotide polymorphisms (SNPs) for hypothesizing significant biological pathways of gastric cancer (GC). We performed an Identify Candidate Causal SNPs and Pathways (ICSNPathway) analysis using a GC genome-wide association study (GWAS) dataset, including 472,342 SNPs in 2,240 GC cases and 3,302 controls of Asian ethnicity. By integrating linkage disequilibrium analysis, functional SNP annotation, and pathway-based analysis, seven candidate SNPs, four genes and 12 pathways were selected. The ICSNPathway analysis produced 4 hypothetical mechanisms of GC: (1) rs4745 and rs12904???EFNA1???ephrin receptor binding; (2) rs1801019???UMPS???drug and pyrimidine metabolism; (3) rs364897???GBA???cyanoamino acid metabolism; and (4) rs11187870, rs2274223, and rs3765524???PLCE1???lipid biosynthetic process, regulation of cell growth, and cation homeostasis. This pathway analysis using GWAS dataset suggests that the 4 hypothetical biological mechanisms might contribute to GC susceptibility.

SUBMITTER: Lee JH

PROVIDER: S-EPMC4431986 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic variants and risk of gastric cancer: a pathway analysis of a genome-wide association study.

Lee Ju-Han JH Kim Younghye Y Choi Jung-Woo JW Kim Young-Sik YS

SpringerPlus 20150506

This study aimed to discover candidate single nucleotide polymorphisms (SNPs) for hypothesizing significant biological pathways of gastric cancer (GC). We performed an Identify Candidate Causal SNPs and Pathways (ICSNPathway) analysis using a GC genome-wide association study (GWAS) dataset, including 472,342 SNPs in 2,240 GC cases and 3,302 controls of Asian ethnicity. By integrating linkage disequilibrium analysis, functional SNP annotation, and pathway-based analysis, seven candidate SNPs, fou ...[more]

PMID: 25992311

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Project description:Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs).Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n?=?15,748; controls, n?=?18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n?=?14,160; controls, n?=?12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n?=?12,160; controls, n?=?16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma.We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value?=?1.9?×?10-6; top gene RORA, gene P value?=?0.0003), prostate (pathway P value?=?4.1?×?10-6; top gene ARNTL, gene P value?=?0.0002) and lung cancer (pathway P value?=?6.9?×?10-7; top gene RORA, gene P value?=?2.0?×?10-6), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC).Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition.

Dataset Information

Genetic variants and risk of gastric cancer: a pathway analysis of a genome-wide association study.

Publications

Genetic variants and risk of gastric cancer: a pathway analysis of a genome-wide association study.

Similar Datasets

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