A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry

被引：56

作者：

Bei, Jin-Xin ^{[1
,2
,3
]}

Su, Wen-Hui ^{[4
,5
]}

Ng, Ching-Ching ^{[6
]}

Yu, Kai ^{[7
]}

Chin, Yoon-Ming ^{[6
]}

Lou, Pei-Jen ^{[8
,9
]}

Hsu, Wan-Lun ^{[10
,11
]}

McKay, James D. ^{[12
]}

Chen, Chien-Jen ^{[10
,11
]}

Chang, Yu-Sun ^{[13
,14
]}

Chen, Li-Zhen ^{[1
,2
,3
]}

Chen, Ming-Yuan ^{[1
,2
,3
]}

Cui, Qian ^{[1
,2
,3
]}

Feng, Fu-Tuo ^{[1
,2
,3
]}

Feng, Qi-Shen ^{[1
,2
,3
]}

Guo, Yun-Miao ^{[1
,2
,3
]}

Jia, Wei-Hua ^{[1
,2
,3
]}

Khoo, Alan Soo-Beng ^{[15
]}

Liu, Wen-Sheng ^{[1
,2
,3
]}

Mo, Hao-Yuan ^{[1
,2
,3
]}

Pua, Kin-Choo ^{[16
]}

Teo, Soo-Hwang ^{[17
]}

Tse, Ka-Po ^{[13
,14
]}

Xia, Yun-Fei ^{[1
,2
,3
]}

Zhang, Hongxin ^{[18
]}

Zhou, Gang-Qiao ^{[18
]}

Liu, Jian-Jun ^{[19
]}

Zeng, Yi-Xin ^{[1
,2
,3
,20
]}

Hildesheim, Allan ^{[21
]}

机构：

[1] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510060, Guangdong, Peoples R China

[2] State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China

[3] Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China

[4] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Dept Biomed Sci, Taoyuan, Taiwan

[5] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Taoyuan, Taiwan

[6] Univ Malaya, Fac Sci, Inst Biol Sci, Kuala Lumpur, Malaysia

[7] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[8] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan

[9] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan

[10] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan

[11] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

[12] Int Agcy Res Canc, Genet Canc Susceptibil Grp, 150 Cours Albert Thomas, F-69372 Lyon, France

[13] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Taoyuan, Taiwan

[14] Chang Gung Univ, Grad Inst Biomed Sci, Taoyuan, Taiwan

[15] Inst Med Res, Canc Res Ctr, Mol Pathol Unit, Kuala Lumpur 50588, Malaysia

[16] Hosp Pulau Pinang, Dept Otorhinolaryngol, George Town, Malaysia

[17] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia

[18] Beijing Inst Radiat Med, Dept Genom & Prote, Beijing Proteome Res Ctr, Beijing, Peoples R China

[19] Genome Inst Singapore, 60 Biopolis St,Genome 02-01, Singapore 0201, Singapore

[20] Peking Union Med Coll, Beijing 100021, Peoples R China

[21] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2016年 / 25卷 / 01期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

GENOME-WIDE ASSOCIATION; RISK; TELOMERASE; SUSCEPTIBILITY; INFECTION; NPC;

D O I：

10.1158/1055-9965.EPI-15-0144

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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 x 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 x 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 x 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 x 10(-8), P = 7.0 x 10(-7), and P = 8.4 x 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. (C) 2015 AACR.

引用

页码：188 / 192

页数：5

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