Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.

Authors:
Christian C Abnet Zhaoming Wang Xin Song Nan Hu Fu-You Zhou Neal D Freedman Xue-Min Li Kai Yu Xiao-Ou Shu Jian-Min Yuan Wei Zheng Sanford M Dawsey Linda M Liao Maxwell P Lee Ti Ding You-Lin Qiao Yu-Tang Gao Woon-Puay Koh Yong-Bing Xiang Ze-Zhong Tang Jin-Hu Fan Charles C Chung Chaoyu Wang William Wheeler Meredith Yeager Jeff Yuenger Amy Hutchinson Kevin B Jacobs Carol A Giffen Laurie Burdett Joseph F Fraumeni Margaret A Tucker Wong-Ho Chow Xue-Ke Zhao Jiang-Man Li Ai-Li Li Liang-Dan Sun Wu Wei Ji-Lin Li Peng Zhang Hong-Lei Li Wen-Yan Cui Wei-Peng Wang Zhi-Cai Liu Xia Yang Wen-Jing Fu Ji-Li Cui Hong-Li Lin Wen-Liang Zhu Min Liu Xi Chen Jie Chen Li Guo Jing-Jing Han Sheng-Li Zhou Jia Huang Yue Wu Chao Yuan Jing Huang Ai-Fang Ji Jian-Wei Kul Zhong-Min Fan Jian-Po Wang Dong-Yun Zhang Lian-Qun Zhang Wei Zhang Yuan-Fang Chen Jing-Li Ren Xiu-Min Li Jin-Cheng Dong Guo-Lan Xing Zhi-Gang Guo Jian-Xue Yang Yi-Ming Mao Yuan Yuan Er-Tao Guo Wei Zhang Zhi-Chao Hou Jing Liu Yan Li Sa Tang Jia Chang Xiu-Qin Peng Min Han Wan-Li Yin Ya-Li Liu Yan-Long Hu Yu Liu Liu-Qin Yang Fu-Guo Zhu Xiu-Feng Yang Xiao-Shan Feng Zhou Wang Yin Li She-Gan Gao Hai-Lin Liu Ling Yuan Yan Jin Yan-Rui Zhang Ilyar Sheyhidin Feng Li Bao-Ping Chen Shu-Wei Ren Bin Liu Dan Li Gao-Fu Zhang Wen-Bin Yue Chang-Wei Feng Qirenwang Qige Jian-Ting Zhao Wen-Jun Yang Guang-Yan Lei Long-Qi Chen En-Min Li Li-Yan Xu Zhi-Yong Wu Zhi-Qin Bao Ji-Li Chen Xian-Chang Li Xiang Zhuang Ying-Fa Zhou Xian-Bo Zuo Zi-Ming Dong Lu-Wen Wang Xue-Pin Fan Jin Wang Qi Zhou Guo-Shun Ma Qin-Xian Zhang Hai Liu Xin-Ying Jian Sin-Yong Lian Jin-Sheng Wang Fu-Bao Chang Chang-Dong Lu Jian-Jun Miao Zhi-Guo Chen Ran Wang Ming Guo Zeng-Lin Fan Ping Tao Tai-Jing Liu Jin-Chang Wei Qing-Peng Kong Lei Fan Xian-Zeng Wang Fu-Sheng Gao Tian-Yun Wang Dong Xie Li Wang Shu-Qing Chen Wan-Cai Yang Jun-Yan Hong Liang Wang Song-Liang Qiu Alisa M Goldstein Zhi-Qing Yuan Stephen J Chanock Xue-Jun Zhang Philip R Taylor Li-Dong Wang

Hum Mol Genet 2012 May 8;21(9):2132-41. Epub 2012 Feb 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7236, USA.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/dds029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315211PMC
May 2012
79 Reads
21 Citations
6.390 Impact Factor

Publication Analysis

Top Keywords

snps 2q33
12
snps
10
squamous cell
8
genome-wide association
8
association signal
8
meta-analysis genome-wide
8
esophageal squamous
8
cell carcinoma
8
genotyped snps
8
association studies
8
2q33
5
snps identify
4
variants directly
4
haplotypes harbor
4
harbor variants
4
directly responsible
4
identify haplotypes
4
signal snps
4
imputed snps
4
snps strong
4

Similar Publications