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An extended genome-wide association study identifies novel susceptibility loci for nasopharyngeal carcinoma.
Cui, Qian; Feng, Qi-Sheng; Mo, Hao-Yuan; Sun, Jian; Xia, Yun-Fei; Zhang, Hongxing; Foo, Jia Nee; Guo, Yun-Miao; Chen, Li-Zhen; Li, Ming; Liu, Wen-Sheng; Xu, Miao; Zhou, Gangqiao; He, Fuchu; Yu, Xueqing; Jia, Wei-Hua; Liu, Jianjun; Zeng, Yi-Xin; Bei, Jin-Xin.
Afiliação
  • Cui Q; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Feng QS; Department of Experimental Research.
  • Mo HY; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Sun J; Department of Experimental Research.
  • Xia YF; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Zhang H; Department of Nasopharyngeal Carcinoma.
  • Foo JN; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Guo YM; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Chen LZ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences Beijing, Beijing, China.
  • Li M; Human Genetics, Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.
  • Liu WS; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Xu M; Department of Experimental Research.
  • Zhou G; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • He F; Department of Experimental Research.
  • Yu X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Jia WH; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Liu J; Department of Experimental Research.
  • Zeng YX; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
  • Bei JX; Department of Experimental Research.
Hum Mol Genet ; 25(16): 3626-3634, 2016 08 15.
Article em En | MEDLINE | ID: mdl-27436580
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Carcinoma / Transativadores / Neoplasias Nasofaríngeas / Telomerase / Proteínas de Membrana / Proteínas de Neoplasias Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Carcinoma / Transativadores / Neoplasias Nasofaríngeas / Telomerase / Proteínas de Membrana / Proteínas de Neoplasias Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article