Genetic variants in fas signaling pathway genes and risk of gastric cancer
Corresponding Author
Paula L. Hyland
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA
Correspondence to: Paula L. Hyland, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, Maryland 20892, Tel.: 240-276-7225, E-mail: [email protected]Search for more papers by this authorShih-Wen Lin
Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorNan Hu
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorHan Zhang
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorLemin Wang
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorHua Su
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorChaoyu Wang
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorTi Ding
Shanxi Cancer Hospital, Taiyuan, People's Republic (PR) China
Search for more papers by this authorZe-Zhong Tang
Shanxi Cancer Hospital, Taiyuan, People's Republic (PR) China
Search for more papers by this authorJin-Hu Fan
Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic (PR) China
Search for more papers by this authorYou-Lin Qiao
Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic (PR) China
Search for more papers by this authorXiaoqin Xiong
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorWilliam Wheeler
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorCarol Giffen
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorKai Yu
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorJeff Yuenger
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorLaurie Burdett
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorZhaoming Wang
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorStephen J. Chanock
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorMargaret A. Tucker
Human Genetics Program, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorSanford M. Dawsey
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorNeal D. Freedman
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorAlisa M. Goldstein
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorChristian C. Abnet
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorPhilip R. Taylor
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorCorresponding Author
Paula L. Hyland
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA
Correspondence to: Paula L. Hyland, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, Maryland 20892, Tel.: 240-276-7225, E-mail: [email protected]Search for more papers by this authorShih-Wen Lin
Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorNan Hu
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorHan Zhang
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorLemin Wang
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorHua Su
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorChaoyu Wang
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorTi Ding
Shanxi Cancer Hospital, Taiyuan, People's Republic (PR) China
Search for more papers by this authorZe-Zhong Tang
Shanxi Cancer Hospital, Taiyuan, People's Republic (PR) China
Search for more papers by this authorJin-Hu Fan
Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic (PR) China
Search for more papers by this authorYou-Lin Qiao
Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic (PR) China
Search for more papers by this authorXiaoqin Xiong
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorWilliam Wheeler
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorCarol Giffen
Information Management Services, Inc, Silver Spring, MD, USA
Search for more papers by this authorKai Yu
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorJeff Yuenger
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorLaurie Burdett
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorZhaoming Wang
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorStephen J. Chanock
Core Genotyping Facility, NCI-Frederick, SAIC-Frederick Inc, and Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
Search for more papers by this authorMargaret A. Tucker
Human Genetics Program, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorSanford M. Dawsey
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorNeal D. Freedman
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorAlisa M. Goldstein
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorChristian C. Abnet
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA
Search for more papers by this authorPhilip R. Taylor
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Search for more papers by this authorAbstract
Populations in north central China are at high risk for gastric cancers (GC), and altered FAS-mediated cell signaling and/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling-related genes using a pathway-based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome-wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene- and pathway-based associations were tested using the adaptive rank-truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway-based associations were observed for Fas signaling with risk of overall GC (p = 5.5E-04) and GCA (p = 6.3E-03), but not GNCA (p= 8.1E-02). Among examined genes in the Fas signaling pathway, MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2 and IKBKB were associated with risk of GC (nominal p < 0.05), and FAF1 and MAPK8 were significantly associated with risk of both GCA and GNCA (nominal p< 0.05). Our examination of genetic variation in the Fas signaling pathway is consistent with an association of altered Fas signaling and/or apoptosis with risk of GC. As one of the first attempts to investigate a pathway-level association, our results suggest that these genes and the Fas signaling pathway warrant further evaluation in relation to GC risk in other populations.
Abstract
What's new?
The bacteria H. pylori is known to cause gastric cancer, but genetic changes can also contribute, particularly in high-risk populations. Identifying these genetic changes in patients could help clinicians make more accurate prognosis of gastric cancer. These authors looked at variation in genes of the Fas signaling pathway, searching for a connection with GC in a high-risk Chinese population. They found that changes in ten specific genes contributed to GC risk in the population, suggesting further work to investigate the functions of those genes.
Supporting Information
*Published 2013. This article is a US Government work and, as such, is in the public domain of the United States of America.Additional Supporting Information may be found in the online version of this article
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