Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach
Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach
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DOI：
10.1002/ijc.24529
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发表时间：
2009-10-15
影响因子：
6.4
通讯作者：
Pawlita, Michael
中科院分区：
文献类型：
--
作者：
Castro, Felipe A.;Haimila, Katri;Pawlita, Michael
高危人乳头瘤病毒（hrHPV）感染是宫颈癌（CxCa）的主要危险因素。遗传易感性在该疾病中的作用已被提出，但现有数据缺乏一致性。我们对来自两个瑞典人群的 973 例 CxCa 病例和 1,763 例匹配对照进行了巢式病例对照研究，以检查常见遗传变异与 CxCa 风险之间的关联。根据已报道的与 HPV 感染或宫颈癌发展的关联或机制合理性，选择了人类白细胞抗原 (HLA) 等位基因和 14 个基因中的 24 个其他多态性。使用多重 PCR 和 Luminex 技术进行基因分型。观察到 CxCa 与各种多态性显着相关：IL-6 基因中的 rs1800797（比值比 [OR] = 0.88，95% 置信区间 [CI]：0.79-0.99）；对于携带稀有等位基因的个体，LTA 基因中的 rs1041981（OR = 0.87，95% CI：0.78-0.98）和 CCND1 基因中的 rs9344（OR = 1.14，95% CI：1.02-1.27）。此外，HLA II 类 DRB1 基因座的等位基因 0401 和 1501 与风险增加相关（OR = 1.23，95% CI：1.04-1.45 和 OR = 1.29，95% CI：1.11-1.50），等位基因 1301 与风险降低相关（OR = 0.59，95% CI：1.04-1.45）。 0.47-0.73）。 CCND1 和 HLA*DRB1 等位基因的影响与吸烟的影响无关。我们没有发现风险与先天免疫系统相关基因的多态性存在任何关联。总之，我们的研究为由于免疫系统和细胞周期相关基因的变异而导致对 CxCa 的遗传易感性提供了证据。 (C)2009年UICC
High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (C) 2009 UICC