https://scholars.lib.ntu.edu.tw/handle/123456789/518215
標題: | A GWAS meta-analysis and replication study identifies a novel locus within CLPTM1L/TERT associated with nasopharyngeal carcinoma in individuals of Chinese ancestry | 作者: | Bei J.-X Su W.-H Ng C.-C Yu K Chin Y.-M PEI-JEN LOU Hsu W.-L McKay J.D Chen C.-J Chang Y.-S Chen L.-Z Chen M.-Y Cui Q Feng F.-T Feng Q.-S Guo Y.-M Jia W.-H Khoo A.S.-B Liu W.-S Mo H.-Y Pua K.-C Teo S.-H Tse K.-P Xia Y.-F Zhang H Zhou G.-Q Liu J.-J Zeng Y.-X Hildesheim A International Nasopharyngeal Carcinoma (NPC) Genetics Working Group |
公開日期: | 2016 | 出版社: | American Association for Cancer Research Inc. | 卷: | 25 | 期: | 1 | 起(迄)頁: | 188-192 | 來源出版物: | Cancer Epidemiology Biomarkers and Prevention | 摘要: | Background: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. Methods: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. Results: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 × 10-13). Our results also provide support for associations reported from published NPC GWAS - rs6774494 (P = 1.5 × 10-12; located in the MECOM gene region), rs9510787 (P = 5.0 × 10-10; located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10-8, P = 7.0 × 10-7, and P = 8.4 × 10-7, respectively; located in the CDKN2A/B gene region). Conclusions: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity. Impact: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. ?2015 AACR. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84955305525&doi=10.1158%2f1055-9965.EPI-15-0144&partnerID=40&md5=76a482e7bcb9f5d1e39fcf58b2d07acc https://scholars.lib.ntu.edu.tw/handle/123456789/518215 |
ISSN: | 1055-9965 | DOI: | 10.1158/1055-9965.EPI-15-0144 | SDG/關鍵字: | CLPTM1L protein, human; membrane protein; telomerase; TERT protein, human; tumor protein; Asian continental ancestry group; case control study; gene locus; genetic predisposition; genetics; genome-wide association study; haplotype; human; meta analysis; nasopharynx tumor; pathology; prognosis; single nucleotide polymorphism; Asian Continental Ancestry Group; Case-Control Studies; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Humans; Membrane Proteins; Nasopharyngeal Neoplasms; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prognosis; Telomerase |
顯示於: | 醫學系 |
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