title: An extended genome-wide association study identifies novel susceptibility loci for nasopharyngeal carcinoma.
abstract: To further identify novel susceptibility loci of nasopharyngeal carcinoma (NPC), we here extended our previous genome-wide association study (GWAS) by boosting statistical power with larger sample size and validating more SNPs in the ranking list based on the GWAS P-values. The discovery stage consisting of 463,250 SNPs in 1,583 cases and 2,979 controls of southern Chinese ancestry revealed 1,257 top SNPs to be associated with NPC, which were brought forward for validation in 1,925 cases and 1,947 controls of southern Chinese. Further, 11 SNPs were selected for another independent validation in 3,538 cases and 3,644 controls of southern Chinese. The joint analysis with 7,046 cases and 8,570 controls resulted in two associations surpassing genome-wide significance (P < 5 × 10-8), including TERT-CLPTM1L at chromosome 5p15 (rs401681; P = 2.65 × 10-14; odds ratio, OR = 0.82) and CIITA at chromosome 16p13 (rs6498114; P = 4.01 × 10-9; OR = 0.87). Conditional analysis revealed that rs401681 accounts for all the tested associations at TERT-CLPTM1L locus, which has been linked with multiple cancers' susceptibilities. Moreover, bioinformatics analyses showed that both SNPs are located in the regulatory regions and correlated with the expression of nearby genes (rs401681 for CLPTM1L and TERT, and rs6498114 for CIITA). CLPTM1L and TERT have been implicated in cancers, and CIITA is considered as the "master control factor" for the expression of NPC-associated MHC class II genes. These suggested that both SNPs might be functional. Altogether, our findings expand our understanding of the genetic contribution to NPC risk and provide novel biological insights into NPC pathogenesis.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Feng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Nasopharyngeal Carcinoma.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Mo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences Beijing, Beijing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Yun-Miao
authors.initials: YM
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences Beijing, Beijing, China.
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences Beijing, Beijing, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Department of Experimental Research.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.|Beijing Hospital, Beijing, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine beijx@sysucc.org.cn.|Department of Experimental Research.|Human Genetics, Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
mesh_terms: D044466:Asian People; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C422445:CLPTM1L protein, human; C083728:MHC class II transactivator protein; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C509186:TERT protein, human; D019098:Telomerase