title: Replication of a genome-wide case-control study of esophageal squamous cell carcinoma.
abstract: In a previous pilot case-control study of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) and matched controls from a high-risk area in China, we identified 38 single nucleotide polymorphisms (SNPs) associated with ESCC located in or near one of 33 genes. In our study, we attempted to replicate the results of these 38 gene-related SNPs in a new sample of 300 ESCC cases and 300 matched controls from the same study conducted in Shanxi Province, China. Among 36 evaluable SNPs, 4 were significant in one or more analyses, including SNPs located in EPHB1, PGLYRP2, PIK3C3 and SLC9A9, although the odds ratios (ORs) for these genotypes were modest. Associations were found with EPHB1/rs1515366 (OR 0.92, 95% CI 0.86-0.99; p = 0.019), PIK3C3/rs52911 (OR 0.93, 95% CI 0.88-0.99; p = 0.02) and PGLYRP2/rs959117 (OR 0.93, 95% CI, 0.86-1.01; p = 0.061) in general linear models (additive mode); and the genotype distribution differed between cases and controls for SLC9A9/rs956062 (p = 0.024). To examine these 4 genes in more detail, 40 HapMap-based tag SNPs from these 4 genes were evaluated in the same subjects and 7 additional SNPs associated with ESCC were identified. Further confirmation of these findings in other populations and other studies are needed to determine if the signals from these SNPs are indirectly associated due to linkage disequilibrium, or are directly related to biologic function and the development of ESCC.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rm 7112, Bethesda, MD 20892-7236, USA. davidng@mail.nih.gov
authors.forename: David
authors.initials: D
authors.lastname: Ng
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.forename: Ze-Zhong
authors.initials: ZZ
authors.lastname: Tang
authors.forename: Xiao-You
authors.initials: XY
authors.lastname: Han
authors.forename: Howard H
authors.initials: HH
authors.lastname: Yang
authors.forename: Maxwell P
authors.initials: MP
authors.lastname: Lee
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors