Hildesheim Allan, Apple Raymond J, Chen Chien-Jen, Wang Sophia S, Cheng Yu-Juen, Klitz William, Mack Steven J, Chen I-How, Hsu Mow-Ming, Yang Czau-Siung, Brinton Louise A, Levine Paul H, Erlich Henry A
Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rm. 7062, Rockville, MD 20852, USA.
J Natl Cancer Inst. 2002 Dec 4;94(23):1780-9. doi: 10.1093/jnci/94.23.1780.
Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC.
We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred.
We found a consistent association between HLA-A0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B4601, which is in linkage disequilibrium with HLA-A0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A0207 and HLA-B4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A3303-B5801/2-DRB10301-DQB10201/2-DPB10401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4).
The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.
鼻咽癌（NPC）在中国人群中的发病率极高，且与爱泼斯坦 - 巴尔病毒（EBV）有关。人类白细胞抗原（HLA）多态性似乎在鼻咽癌中发挥作用，因为它们在对病毒的免疫反应中至关重要。我们在台湾的一项病例对照研究中使用高分辨率HLA基因分型，系统地评估各种HLA等位基因与鼻咽癌之间的关联。
我们按照年龄、性别和地理居住地将366例鼻咽癌患者与318名对照者进行匹配。对参与者进行访谈并采集血样进行基因分型。HLA I类（A和B）和II类（DRB1、DQA1、DQB1和DPB1）基因的高分辨率（基于聚合酶链反应）基因分型分两个阶段进行。在第一阶段，对210例患者和183名对照者进行了完全基因分型。在第二阶段，在另外156例患者和135名对照者中评估了在第一阶段分析中与鼻咽癌相关的等位基因。推断出扩展单倍型。
我们发现HLA - A0207（在中国人群中常见，但在白种人中不常见）与鼻咽癌之间存在一致的关联（优势比[OR]=2.3，95%置信区间[CI]=1.5至3.5），而HLA - A0201（白种人中最常见的HLA - A2等位基因）与鼻咽癌之间无关联（OR = 0.79，95% CI = 0.55至1.2）。与HLA - A0207处于连锁不平衡状态的HLA - B4601个体患鼻咽癌的风险增加（OR = 1.8，95% CI = 1.2至2.5），HLA - A0207和HLA - B4601个体也是如此（OR = 2.8，95% CI = 1.7至4.4）。HLA - A1101纯合个体患鼻咽癌的风险降低（OR = 0.24，95% CI = 0.13至0.46）。特定于该族群的扩展单倍型HLA - A3303 - B5801/2 - DRB10301 - DQB10201/2 - DPB10401与鼻咽癌风险在统计学上显著增加相关（OR = 2.6，95% CI = 1.1至6.4）。
HLA - A2与鼻咽癌的关联仅限于HLA - A*0207，这可能解释了之前在中国人群而非白种人中观察到的HLA - A2与鼻咽癌的关联。与鼻咽癌相关的扩展单倍型可能部分解释了该族群中较高的鼻咽癌发病率。
