HLA DRB等位基因多态性与人类乳头瘤病毒感染相关的宫颈癌风险：一项中国的人群研究。

HLA DRB allele polymorphisms and risk of cervical cancer associated with human papillomavirus infection: a population study in China.

作者信息

Zhao M, Qiu L, Tao N, Zhang L, Wu X, She Q, Zeng F, Wang Y, Wei S, Wu X

机构信息

Institute of Virology, School of Medicine,Wuhan University, Wuhan, Hubei, China.

出版信息

Eur J Gynaecol Oncol. 2013;34(1):54-9.

PMID:23590002

Abstract

OBJECTIVE

Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer. Environmental, behavioral, and ill-defined genetic factors have also been implicated in the pathogenesis of this disease. To determine whether human leukocyte antigen (HLA) DRB alleles are associated with cervical cancer and HPV infections in the Chinese population, HLA genotypes were examined in 69 cervical cancer patients and 201 controls.

MATERIALS AND METHODS

Polymorphisms in HLA-DRB genes were genotyped using oligoneucleotide arrays, and the magnitude of associations was determined by logistic regression analysis.

RESULTS

HLA-DRB113 (OR = 4.01 95% CI, 1.703-9.442) and HLA-DRB13(17) (OR = 2.661 95% CI, 1.267-5.558) were associated with an increased risk of cervical cancer, and DRB109012 (OR = 0.182, 95% CI, 0.079-0.418 and DRB11201 (OR = 0.35 95% CI, 0.142-0.863 were associated with a decreased risk. The risk associations of HPV infection were increased in women carrying the HLA-DRB1*09012 (OR = 1.924; 95% CI, 1.08 -3.427) and DRB3(52)0101 (OR = 7.527 95% CI, 0.909-62.347) alleles. Among cervical cancer patients, the risk associations differed between HPV positive and negative cases for several alleles; increased risk of cervical cancer was associated with DRB3 (52)02/03 (OR, 12.794; 95% CI, 5.007-32.691) and DRB13(17) (OR = 3.48; 95% CI, 1.261-9.604), and decreased risk was associated with DRB109012 and DRB5(51)01/02. Furthermore, HPV16-containing cervical cancer cases differed from non-HPV16 subjects in their positive association with DRB11501 (OR = 4.173; 95% CI, 1.065-16.356) and DRB5(51)*0101/0201, and their negative association with DRB4(53)*0101 (OR = 0.329; 95% CI,0.122-0.888).

CONCLUSIONS

The present results provide further evidence that certain HLA class II allele polymorphisms are involved in the genetic susceptibility to cervical cancer and HPV infection in the Chinese population from an area with a high incidence of this neoplasia.

摘要

目的

高危型人乳头瘤病毒（HPV）持续感染是宫颈癌的主要病因。环境、行为及不明的遗传因素也与该疾病的发病机制有关。为确定中国人群中人类白细胞抗原（HLA）DRB等位基因是否与宫颈癌及HPV感染相关，对69例宫颈癌患者和201例对照进行了HLA基因分型。

材料与方法

采用寡核苷酸阵列对HLA-DRB基因多态性进行基因分型，并通过逻辑回归分析确定关联强度。

结果

HLA-DRB113（比值比[OR]=4.01，95%可信区间[CI]为1.703 - 9.442）和HLA-DRB13(17)（OR = 2.661，95% CI为1.267 - 5.558）与宫颈癌风险增加相关，而DRB109012（OR = 0.182，95% CI为0.079 - 0.418）和DRB11201（OR = 0.35，95% CI为0.142 - 0.863）与风险降低相关。携带HLA-DRB1*09012（OR = 1.924；95% CI为1.08 - 3.427）和DRB3(52)0101（OR = 7.527，95% CI为0.909 - 62.347）等位基因的女性HPV感染风险关联增加。在宫颈癌患者中，几个等位基因在HPV阳性和阴性病例中的风险关联不同；宫颈癌风险增加与DRB3 (52)02/03（OR，12.794；95% CI为5.007 - 32.691）和DRB13(17)（OR = 3.48；95% CI为1.261 - 9.604）相关，风险降低与DRB109012和DRB5(51)01/02相关。此外，含HPV16的宫颈癌病例与非HPV16受试者在与DRB11501（OR = 4.173；95% CI为1.065 - 16.356）和DRB5(51)*0101/0201的正相关以及与DRB4(53)*0101（OR = 0.329；95% CI为0.122 - 0.888）的负相关方面存在差异。