Genome-wide association study in esophageal cancer using GeneChip mapping 10K array

被引:76
作者
Hu, N
Wang, CY
Hu, Y
Yang, HH
Giffen, C
Tang, ZZ
Han, XY
Goldstein, AM
Emmert-Buck, MR
Buetow, KH
Taylor, PR
Lee, MP
机构
[1] NCI, Lab Populat Genet, Canc Res Ctr, Bethesda, MD 20892 USA
[2] NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA
[3] NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA
[4] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
[5] Informat Management Serv Inc, Silver Spring, MD USA
[6] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China
关键词
D O I
10.1158/0008-5472.CAN-04-3247
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Whole genome association studies of complex human diseases represent a new paradigm in the postgenomic era. In this study, we report application of the Affymetrix, Inc. (Santa Clara, CA) high-density single nucleotide polymorphism (SNP) array containing 11,555 SNPs in a pilot case-control study of esophageal squamous cell carcinoma (ESCC) that included the analysis of germ line samples from 50 ESCC patients and 50 matched controls. The average genotyping call rate for the 100 samples analyzed was 96%. Using the generalized linear model (GLM) with adjustment for potential confounders and multiple comparisons, we identified 37 SNPs associated with disease, assuming a recessive mode of transmission; similarly, 48 SNPs were identified assuming a dominant mode and 53 SNPs in a continuous mode. When the 37 SNPs identified from the GLM recessive mode were used in a principal components analysis, the first principal component correctly predicted 46 of 50 cases and 47 of 50 controls. Among all the SNPs selected from GLMs for the three modes of transmission, 39 could be mapped to I of 33 genes. Many of these genes are involved in various cancers, including GASC1, shown previously to he amplified in ESCCs, and EPHB1 and PIK3C3. In conclusion, we have shown the feasibility of the Affymetrix 10K SNP array in genome-wide association studies of common cancers and identified new candidate loci to study in ESCC.
引用
收藏
页码:2542 / 2546
页数:5
相关论文
共 28 条
[1]   High-resolution haplotype structure in the human genome [J].
Daly, MJ ;
Rioux, JD ;
Schaffner, SE ;
Hudson, TJ ;
Lander, ES .
NATURE GENETICS, 2001, 29 (02) :229-232
[2]   Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma [J].
Hao, BT ;
Wang, HJ ;
Zhou, KX ;
Li, Y ;
Chen, XP ;
Zhou, GQ ;
Zhu, YP ;
Miao, XP ;
Tan, W ;
Wei, QY ;
Lin, DX ;
He, FC .
CANCER RESEARCH, 2004, 64 (12) :4378-4384
[3]   Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China [J].
Hu, N ;
Li, WJ ;
Su, H ;
Wang, CY ;
Goldstein, AM ;
Albert, PS ;
Emmert-Buck, MR ;
Kong, LH ;
Roth, MJ ;
Dawsey, SM ;
He, LJ ;
Cao, SF ;
Ding, T ;
Giffen, C ;
Taylor, PR .
CANCER DETECTION AND PREVENTION, 2003, 27 (02) :132-138
[4]  
Hu N, 2001, CLIN CANCER RES, V7, P883
[5]  
Hu N, 2000, GENE CHROMOSOME CANC, V27, P217, DOI 10.1002/(SICI)1098-2264(200003)27:3<217::AID-GCC1>3.0.CO
[6]  
2-A
[7]  
*IARC, 1988, IARC MON EV CARC RIS, P153
[8]   High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines [J].
Jänne, PA ;
Li, C ;
Zhao, XJ ;
Girard, L ;
Chen, TH ;
Minna, J ;
Christiani, DC ;
Johnson, BE ;
Meyerson, M .
ONCOGENE, 2004, 23 (15) :2716-2726
[9]   Large-scale genotyping of complex DNA [J].
Kennedy, GC ;
Matsuzaki, H ;
Dong, SL ;
Liu, WM ;
Huang, J ;
Liu, GY ;
Xu, X ;
Cao, MQ ;
Chen, WW ;
Zhang, J ;
Liu, WW ;
Yang, G ;
Di, XJ ;
Ryder, T ;
He, ZJ ;
Surti, U ;
Phillips, MS ;
Boyce-Jacino, MT ;
Fodor, SPA ;
Jones, KW .
NATURE BIOTECHNOLOGY, 2003, 21 (10) :1233-1237
[10]  
Li J Y, 1982, Natl Cancer Inst Monogr, V62, P113