中国北方汉族女性HLA-DP/DQ基因多态性与宫颈癌易感性的关联研究

Association Study on Genetic Polymorphisms of HLA-DP/DQ and Susceptibility to Cervical Cancer in North Chinese Women

[目的]探讨中国北方女性HL4-DP和HLA—D0的基因多态性与宫颈癌遗传易感性的关联。[方法]采用病例对照研究设计，收集北方汉族人群中831例新发宫颈癌患者和573例按年龄地区匹配的正常女性作为对照。应用TaqMan基因分型方法检测HLA-DP基因上的rs3077和rs9277535两个位点，以及HLA-D0基因上的rs2856718和rs7453920位点。[结果]经Logistic回归分析显示．在调整年龄、吸烟、绝经状况、肿瘤家族史和活产胎次等因素后，携带HLA—DPrs3077GA／AA基因型和ⅡLA—DPrs9277535GA／AA基因型者分别是HLA—DPGG基因宫颈癌发病风险的2．77倍（调整OR=2．77，95％CI：2．13～3．61）和1．66倍（调整OR=I．66，95％CI：1．25～2．20）。两位点的联合分析显示，与携带0个危险等位基因的个体相比，携带1—4个危险等位基因的个体患宫颈癌的风险增加（调整OR=2．38，95％CI：1．74～3．27），且随着携带危险等位基因个数的增加，宫颈癌的发病风险也逐步增加，呈现明显的剂量反应关系（P趋势=1．19×10-11）。但HLA—D0基因上的rs2856718和rs7453920与宫颈癌的发病风险无显著性关联（P〉0．05）。『结论]HLA—DP基因上的rs3077和rs9277535可能是中国北方女性宫颈癌的易感性位点，但该结论还需要大样本前瞻性研究的验证及功能学研究的解释。

[Purpose] To investigate the relationship of HLA-DP and HLA-DQ genetic polymor- phisms with susceptibility to cervical cancer in North Chinese women. [Methods] A case-control study was conducted in 831 cases with cervical cancer and 573 health control matched by age and area. HLA-DP （rs3077 and rs9277535） and HLA-DQ （rs2856718 and rs7453920） was detected by TaqMan allelic discrimination assay. [ Results ] Logistic regression analysis showed that the cervical cancer risk in person with HLA-DP rs3077 GMAA was 2.77 times of that in person with HLA-DP rs3077 GG （95%CI： 2.13-3.61）,and HLA-DP rs9277535 GA/AA was 1.66 times （95%Ch 1.25- 2.20） after ajusted by age,somking,menopausal status,family history of cancer and parity.When combining the effects of HLA-DP rs3077 and rs9277535, subjects carrying ＂1〉 1＂ variant alleles increased risk of cervical cancer （OR=2.38,95%CI：l.74-3.27）,compared with those carrying ＂0＂ variant allele. And cervical cancer risk significantly increased with the increasing number of vari- ant alleles of the two SNPs in a dose-dependent manner（Pfor trend=l.19×l0-11）. However,significant association between HLA-DQ rs2856718 and rs7453920 with cervical risk was not observed （PM）.05）. [Conclusions] HLA-DP rs3077 and rs9277535 may be susceptibility markers for cervical cancer in North Chinese females. Further validation studies with large sample size,biological function analysis are needed.