Genome-wide association study in esophageal cancer using GeneChip mapping 10K array.
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 1 of 33 genes. Many of these genes are involved in various cancers, including GASC1, shown previously to be 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.
Hu
Nan
N
Cancer Prevention Studies Branch, Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Wang
Chaoyu
C
Hu
Ying
Y
Yang
Howard H
HH
Giffen
Carol
C
Tang
Ze-Zhong
ZZ
Han
Xiao-Yu
XY
Goldstein
Alisa M
AM
Emmert-Buck
Michael R
MR
Buetow
Kenneth H
KH
Taylor
Philip R
PR
Lee
Maxwell P
MP
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors