Document Detail


Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.
MedLine Citation:
PMID:  23103227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.
Authors:
Guangfu Jin; Hongxia Ma; Chen Wu; Juncheng Dai; Ruyang Zhang; Yongyong Shi; Jiachun Lu; Xiaoping Miao; Meilin Wang; Yifeng Zhou; Jiaping Chen; Huizhang Li; Shandong Pan; Minjie Chu; Feng Lu; Dianke Yu; Yue Jiang; Jing Dong; Lingmin Hu; Yijiang Chen; Lin Xu; Yongqian Shu; Shiyang Pan; Wen Tan; Baosen Zhou; Daru Lu; Tangchun Wu; Zhengdong Zhang; Feng Chen; Xinru Wang; Zhibin Hu; Dongxin Lin; Hongbing Shen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-25
Journal Detail:
Title:  American journal of human genetics     Volume:  91     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-01-14     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  928-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Epidemiology and Biostatistics and Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Aged
Asian Continental Ancestry Group / genetics*
Carcinoma, Squamous Cell / epidemiology,  genetics
China / epidemiology
Chromosomes, Human, Pair 6*
Chromosomes, Human, Pair 7*
Esophageal Neoplasms / epidemiology,  genetics
Female
Genetic Predisposition to Disease
Genetic Variation*
Genome-Wide Association Study
Humans
Lung Neoplasms / epidemiology,  genetics
Male
Middle Aged
Neoplasms, Multiple Primary / epidemiology,  genetics*
Risk*
Stomach Neoplasms / epidemiology,  genetics
Grant Support
ID/Acronym/Agency:
U19 CA148127/CA/NCI NIH HHS
Comments/Corrections

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