Faculty Collaboration Database

Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese. Am J Hum Genet 2012 Nov 02;91(5):928-34

Date

10/30/2012

Pubmed ID

23103227

Pubmed Central ID

PMC3487121

DOI

10.1016/j.ajhg.2012.09.009

Scopus ID

2-s2.0-84868487907 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

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.

Author List

Jin G, Ma H, Wu C, Dai J, Zhang R, Shi Y, Lu J, Miao X, Wang M, Zhou Y, Chen J, Li H, Pan S, Chu M, Lu F, Yu D, Jiang Y, Dong J, Hu L, Chen Y, Xu L, Shu Y, Pan S, Tan W, Zhou B, Lu D, Wu T, Zhang Z, Chen F, Wang X, Hu Z, Lin D, Shen H

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Carcinoma, Squamous Cell
China
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 7
Esophageal Neoplasms
Female
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasms, Multiple Primary
Risk
Stomach Neoplasms