A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci

• Published in: Nature genetics Vol. 42; no. 7; pp. 599 - 603
• Main Authors: Bei, Jin-Xin, Li, Yi, Jia, Wei-Hua, Feng, Bing-Jian, Zhou, Gangqiao, Chen, Li-Zhen, Feng, Qi-Sheng, Low, Hui-Qi, Zhang, Hongxing, He, Fuchu, Tai, E Shyong, Kang, Tiebang, Liu, Edison T, Liu, Jianjun, Zeng, Yi-Xin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2010; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/69; 631/208/727/2000; 692/699/67/1536; Agriculture; Animal Genetics and Genomics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; China; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene Function; Genetic aspects; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genetic susceptibility; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study - methods; Genotype; Human Genetics; Humans; Independent sample; letter; MDS1 and EVI1 Complex Locus Protein; Medical sciences; Nasopharyngeal cancer; Nasopharyngeal Neoplasms - ethnology; Nasopharyngeal Neoplasms - genetics; Neoplasm Proteins - genetics; Odds Ratio; Otorhinolaryngology. Stomatology; Polymorphism, Single Nucleotide; Principal components analysis; Proto-Oncogenes - genetics; Receptors, Tumor Necrosis Factor - genetics; Regression analysis; Risk Factors; Sample size; Science; Single nucleotide polymorphisms; Studies; Transcription Factors - genetics; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; China; Singapore; ENT disease; Pharynx disease; Identification; Malignant tumor; Nasopharynx carcinoma; Locus; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.601

Yi-Xin Zeng and colleagues performed a genome-wide association study for nasopharyngeal cancer in Southern Chinese. The authors report three new susceptibility loci for nasopharyngeal cancer. To identify genetic susceptibility loci for nasopharyngeal carcinoma (NPC), a genome-wide association study was performed using 464,328 autosomal SNPs in 1,583 NPC affected individuals (cases) and 1,894 controls of southern Chinese descent. The top 49 SNPs from the genome-wide association study were genotyped in 3,507 cases and 3,063 controls of southern Chinese descent from Guangdong and Guangxi. The seven supportive SNPs were further confirmed by transmission disequilibrium test analysis in 279 trios from Guangdong. We identified three new susceptibility loci, TNFRSF19 on 13q12 (rs9510787, P combined = 1.53 × 10 −9 , odds ratio (OR) = 1.20), MDS1-EVI1 on 3q26 (rs6774494, P combined = 1.34 × 10 −8 , OR = 0.84) and the CDKN2A - CDKN2B gene cluster on 9p21 (rs1412829, P combined = 4.84 × 10 −7 , OR = 0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 ( P combined = 4.88 × 10 −67 , OR = 0.58), rs2894207 ( P combined = 3.42 × 10 −33 , OR = 0.61) and rs28421666 ( P combined = 2.49 × 10 −18 , OR = 0.67). Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of pathways related to TNFRSF19 and MDS1-EVI1 in addition to HLA molecules.