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）具有非常独特的地理和种族分布，在中国东南部的华人中发病率较高，而在白人人群中发病率要低得多。虽然爱泼斯坦巴尔病毒（EBV）感染被认为是癌症发生所必需的，但其他遗传和外源因素也被认为很重要。为了调查与鼻咽癌病因相关的遗传、饮食、职业和行为因素，台湾进行了多项研究，包括约 1,000 名个体的病例对照研究和约 3,000 名个体（350 个家庭）的多重家庭研究。迄今为止，我们的结果表明风险与 CYP2E1 酶和几种 DNA 修复基因的特定变体、HLA 和 KIR 基因的特定模式以及长期吸烟之间存在关联。儿童期和断奶期间大量摄入亚硝胺和亚硝酸盐也与风险增加有关。职业接触木屑似乎也会影响风险；相反，甲醛暴露并不是一个重要的危险因素。我们的家庭研究中发现的外源性危险因素与我们的病例对照研究中观察到的相似。对鼻咽肿瘤和正常细胞基因表达谱的评估表明，参与 DNA 修复和亚硝胺代谢的基因参与了鼻咽癌的发病机制。我们基于组织的表达研究的结果还表明 NPC 中 14 号染色体端粒末端杂合性丢失的可能性，并且 NPC 肿瘤细胞内的 EBV 基因表达影响参与免疫呈递的宿主基因的表达。这表明 EBV 能够逃避鼻咽癌免疫监视的可能机制。我们的研究表明，与普通人群相比，来自 NPC 多重家族的 U 受影响个体的 EBV 抗体水平较高。为了跟进这一发现，我们评估了 EBV 血清学在预测 NPC 多重家族中未受影响个体随后的 NPC 风险方面的价值。 我们观察到，针对多种 EBV 标记物的抗体水平升高的个体在 10 年内患 NPC 的风险增加 4 至 6 倍，但所评估抗体的低特异性表明，在此类基于血清学的测试可以进行之前，需要进行改进。临床上使用。

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