Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Canada.
Int J Cancer. 2012 Aug 1;131(3):E312-9. doi: 10.1002/ijc.27356. Epub 2012 Jan 3.
Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression in tumor cells may enable them to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G polymorphism on risk of high-grade cervical intraepithelial neoplasia (HG-CIN) and cervical cancer in a Canadian population. The authors have analyzed 1,372 women from participants recruited between 2001 and 2009 in the ongoing Biomarkers of Cervical Cancer Risk case-control study. A total of 539 women with histologically confirmed HG-CIN and invasive cancer formed the case series, and 833 women with normal cytology served as controls. Cervical specimens were tested for human papillomavirus (HPV) DNA using the MY09/11 PCR protocol and HLA-G alleles where determined using a direct DNA sequencing procedures. HLA-G polymorphisms were not associated with HG-CIN or HPV infection. However, the risk for invasive cancer was significantly increased with the homozygous genotypes HLA-G01:01:02 [odds ratio (OR) = 3.52, 95% confidence interval (CI): 1.43-8.61, p = 0.006], -G01:06 (OR = 19.1, 95% CI: 2.29-159, p = 0.005) and -G* 3'UTR 14-bp insertion (OR = 2.17, 95% CI: 1.10-4.27, p = 0.020), whereas, the heterozygotic form of the G*01:01:01 wild-type allele was significantly associated with a reduced risk of invasive cancer (OR = 0.31, 95% CI: 0.16-0.59, p < 0.0001) after adjusting for age, HPV infection and ethnicity. These associations were also observed with progression of disease from HG-CIN to invasive cancer among HPV-positive women. These results suggest that HLA-G polymorphism is an independent risk factor for the development of invasive cervical cancer.
人类白细胞抗原（HLA）-G 作为免疫反应的负调节剂，其在肿瘤细胞中的表达可能使它们能够逃避免疫监视。本研究旨在调查 HLA-G 多态性对加拿大人群中高级别宫颈上皮内瘤变（HG-CIN）和宫颈癌风险的影响。作者分析了 2001 年至 2009 年期间参加正在进行的宫颈癌风险生物标志物病例对照研究的 1372 名女性。共有 539 名经组织学证实的 HG-CIN 和浸润性癌女性形成病例系列，833 名细胞学正常的女性作为对照。使用 MY09/11 PCR 方案检测宫颈标本中的人乳头瘤病毒（HPV）DNA，使用直接 DNA 测序程序确定 HLA-G 等位基因。HLA-G 多态性与 HG-CIN 或 HPV 感染无关。然而，侵袭性癌症的风险与 HLA-G01:01:02 纯合基因型显著增加[比值比（OR）=3.52，95%置信区间（CI）：1.43-8.61，p=0.006]，-G01:06（OR=19.1，95%CI：2.29-159，p=0.005）和-G3'UTR 14-bp 插入（OR=2.17，95%CI：1.10-4.27，p=0.020），而 G01:01:01 野生型等位基因的杂合形式与侵袭性癌症的风险降低显著相关（OR=0.31，95%CI：0.16-0.59，p<0.0001），调整年龄、HPV 感染和种族因素后。在 HPV 阳性女性中，从 HG-CIN 进展为浸润性癌时也观察到这些关联。这些结果表明，HLA-G 多态性是浸润性宫颈癌发生的独立危险因素。
