Viral and Host Factors Associated with NPC

与鼻咽癌相关的病毒和宿主因素

• 批准号: 10919005
• 负责人: Eric A Engels
• 金额: $ 24.48万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10919005
• 关键词: Affect; Antibodies; Antibody Specificity; Behavioral; CYP2E1 gene; Case/Control Studies; Caucasians; Childhood; China; Chinese; Chromosome 14; Clinical; Clinical Markers; DNA Repair; DNA Repair Gene; Development; Dust; Environmental Risk Factor; Enzymes; Ethnic Origin; Etiology; Evaluation; Exposure to; Family; Family Study; Formaldehyde; GEM gene; Gene Expression; General Population; Genes; Genetic; Geography; Human Herpesvirus 4; Immune; Immune Evasion; Individual; Infection; Intake; Integration Host Factors; Loss of Heterozygosity; Malignant Neoplasms; Malignant neoplasm of nasopharynx; Nasopharyngeal Neoplasms; Nitrites; Nitrosamine Metabolism; Nitrosamines; Normal Cell; Occupational; Occupational Exposure; Pathogenesis; Pattern; Population; Risk; Risk Factors; Serology; Taiwan; Testing; Tissues; Variant; Viral; Weaning; Wood material; cancer risk; cigarette smoking; dietary; follow-up; high risk population; improved; neoplastic cell

Nasopharyngeal cancer (NPC) has a very distinct geographic and ethnic distribution, occurring at high rates among ethnic Chinese from southeastern China and at much lower rates among Caucasian populations. While infection with the Epstein Barr virus (EBV) is believed to be necessary for development of the cancer, other factors, both genetic and exogenous, are also thought to be important. To investigate genetic, dietary, occupational, and behavioral factors related to the etiology of NPC, several studies were conducted in including a case-control study of approximately 1,000 individuals and a multiplex family study of approximately 3,000 individuals (350 families) in Taiwan. To date, our results suggest an association between risk and specific variants of the enzyme CYP2E1 and several DNA repair genes, specific patterns of HLA and KIR genes, and long-term cigarette smoking. High intakes of nitrosamines and nitrite during childhood and weaning also were associated with increased risks. Occupational exposures to wood dusts also appeared to affect risk; in contrast, formaldehyde exposure was not a significant risk factor. Exogenous risk factors identified within our family study were similar to those observed from our case-control study. Evaluation of gene expression profiles from nasopharynx tumor and normal cells suggest that genes involved in DNA repair and in the metabolism of nitrosamines are involved in NPC pathogenesis. Results from our tissue-based expression studies also suggest the possibility of loss-of-heterozygosity on the telomeric end of chromosome 14 in NPC, and that EBV gene expression within NPC tumor cells affect the expression of host genes involved in immune presentation. This suggests a possible mechanism by which EBV manages to evade immune surrveillance in NPC. Uaffected individuals from NPC multiplex families have been shown in our study to have elevated levels of antibodies against EBV compared to the general population. To follow-up on this finding, we have evaluated the value of EBV serology to predict subsequent NPC risk among unaffected individuals from NPC multiplex families. We observed that individual with elevated antibody levels against several EBV markers are at a 4 to 6-fold increased risk of developing NPC within 10 years, but the low specificity of the antibodies evaluated suggest that improvements are required before such serology-based tests can be used clinically.

鼻咽癌（NPC）具有非常不同的地理和种族分布，在中国东南部的中国族中以高率发生，而白种人人口的速度要低得多。尽管人们认为对爱泼斯坦Barr病毒（EBV）的感染对于癌症的发展是必要的，但遗传和外源性的其他因素也被认为很重要。为了研究与NPC病因相关的遗传，饮食，职业和行为因素，进行了几项研究，包括对台湾大约1,000个个体的病例对照研究和一项多重多重家族研究，对台湾约3,000名个人（350个家庭）进行了多重家庭研究。迄今为止，我们的结果表明，酶CYP2E1的风险与特定变体之间存在关联，以及几种DNA修复基因，HLA和KIR基因的特定模式以及长期吸烟。儿童期和断奶期间的硝基胺和亚硝酸盐的摄入量也与风险增加有关。对木尘的职业暴露似乎也影响了风险。相反，甲醛暴露不是重要的危险因素。我们家庭研究中发现的外源危险因素与我们的病例对照研究中观察到的危险因素相似。评估来自鼻咽肿瘤和正常细胞的基因表达谱，表明参与DNA修复和硝基胺代谢的基因参与NPC发病机理。我们基于组织的表达研究的结果还表明，NPC染色体14染色体端的杂合性丧失的可能性，NPC肿瘤细胞中的EBV基因表达会影响与免疫表现有关的宿主基因的表达。这表明EBV设法逃避了NPC中的免疫投降的可能机制。与普通人群相比，我们的研究中已经证明了来自NPC多重家族的未经无效的个体对EBV的抗体水平升高。为了跟进这一发现，我们评估了EBV血清学的价值，以预测NPC多重多重家族未受影响的个体中随后的NPC风险。 我们观察到，针对几种EBV标记的抗体水平升高的个体在10年内增加了NPC发展的风险4至6倍，但是评估的抗体的低特异性表明，在临床上使用此类基于血清的测试之前，需要进行改进。

项目成果

Lowered risk of nasopharyngeal carcinoma and intake of plant vitamin, fresh fish, green tea and coffee: a case-control study in Taiwan.

• DOI: 10.1371/journal.pone.0041779
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hsu WL;Pan WH;Chien YC;Yu KJ;Cheng YJ;Chen JY;Liu MY;Hsu MM;Lou PJ;Chen IH;Yang CS;Hildesheim A;Chen CJ
• 通讯作者: Chen CJ

Elevated antibodies against Epstein-Barr virus among individuals predicted to carry nasopharyngeal carcinoma susceptibility variants.

预测携带鼻咽癌易感变异体的个体中针对 Epstein-Barr 病毒的抗体升高。

• DOI: 10.1099/jgv.0.001115
• 发表时间: 2018
• 期刊: The Journal of general virology
• 作者: Coghill,AnnaE;Hsu,Wan-Lun;Yang,Qi;Wang,Cheng-Ping;Lou,Pei-Jen;Yu,KellyJ;Yu,Guoqin;Diehl,ScottR;Chen,Chien-Jen;Goldstein,AlisaM;Hildesheim,Allan
• 通讯作者: Hildesheim,Allan

Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma.

• DOI: 10.1038/s41598-021-02788-w
• 发表时间: 2021-12-08
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Liu Z;Sarathkumara YD;Chan JKC;Kwong YL;Lam TH;Ip DKM;Chiu BC;Xu J;Su YC;Proietti C;Cooper MM;Yu KJ;Bassig B;Liang R;Hu W;Ji BT;Coghill AE;Pfeiffer RM;Hildesheim A;Rothman N;Doolan DL;Lan Q
• 通讯作者: Lan Q

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

• DOI: 10.1093/jnci/djad012
• 发表时间: 2023-04-11
• 期刊: Journal of the National Cancer Institute

Development of a Duplex Serological Multiplex Assay for the Simultaneous Detection of Epstein-Barr Virus IgA and IgG Antibodies in Nasopharyngeal Carcinoma Patients.

• DOI: 10.3390/cancers15092578
• 发表时间: 2023-04-30
• 期刊: CANCERS
• 影响因子: 5.2
• 作者: Schieber, Jennifer;Pring, Miranda;Ness, Andy;Liu, Zhiwei;Hsu, Wan-Lun;Brenner, Nicole;Butt, Julia;Waterboer, Tim;Simon, Julia
• 通讯作者: Simon, Julia