Journal
NATURE GENETICS
Volume 46, Issue 9, Pages 1001-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3064
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Funding
- National High-Tech Research and Development Program of China [2009AA022706]
- National Basic Research Program of China [2011CB504303]
- National Natural Science Foundation of China [30721001, 81071783]
- Invitation Team of the Ministry of Education [2008IRTSTHN010]
- 863 High-Tech Key Projects [2012AA02A209, 2012AA02A503, 2012AA02A201]
- Innovation Scientists and Technicians Troop Construction Projects of Henan Province [3047]
- Key Disciplines Revitalization Plan of Zhengzhou University [20132016]
- Collaborative Innovation Center for Esophageal Cancer Research of Henan Province [20132016]
- NCI [R01 CA82729, R37 CA70837, NO2-CP-11010, NO2-SC-66211, NO1-SC-91030, HHSN261200477001C]
- Vanderbilt University
- Shanxi Cancer Hospital and Institute
- Cancer Institute and Hospital of the Chinese Academy of Medical Sciences
- intramural research program of the US NIH/NCI
- Division of Cancer Epidemiology and Genetics
- Center for Cancer Research
- US NIH/NCI [HHSN261200800001E]
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We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS)(1-3) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 x 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 x 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 x 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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