Laboratory for Gynecologic Tumor Immunology, Clinic for Gynecology, Charité-Universitaetsmedizin Berlin.
Int J Gynecol Cancer. 2011 Dec;21(9):1664-71. doi: 10.1097/IGC.0b013e31822b6299.
Host genetic characteristics and environmental factors may correlate with risk for cervical cancer development. Here we describe a retrospective screening study for single nucleotide polymorphisms (SNPs) in genetic markers TP53, MTHFR, CYP1A1, and CYP2E1 in 749 patients.
A multiplex ligation-dependent polymerase chain reaction approach was applied. We used archived material from human papillomavirus tests and correlated SNP genotypes to the corresponding clinical data. Semantic integration was used to identify and evaluate the clinical status from electronic health records.
An association with cervical cancer and high-grade dysplasia was found for the rare homozygous CC genotype (rs4646903) in CYP1A1 (odds ratio [OR], 8.862). Odds ratios were also significantly elevated for heterozygous MTHFR CT genotype (rs1801133; OR, 1.457). No significant association was found in TP53 (rs1042522) and CYP2E1 (rs3813867). In addition, we found smokers at higher risk (OR, 2.688) and identified pregnancies as a significant risk factor (OR, 1.54).
Our protocol enables a feasible way for further retrospective large sample size evaluation of potential genetic markers. This study revealed genetic associations of a rare SNP genotype with cervical dysplasia in one of the largest patient sample to date that warrants further investigation.
宿主遗传特征和环境因素可能与宫颈癌发展的风险相关。在这里，我们描述了一项针对 749 名患者的遗传标记物 TP53、MTHFR、CYP1A1 和 CYP2E1 中单核苷酸多态性（SNP）的回顾性筛选研究。
采用多重连接依赖性聚合酶链反应方法。我们使用人乳头瘤病毒检测的存档材料，并将 SNP 基因型与相应的临床数据相关联。语义集成用于从电子健康记录中识别和评估临床状态。
我们发现 CYP1A1 中罕见的纯合 CC 基因型（rs4646903）与宫颈癌和高级别发育不良相关（比值比 [OR]，8.862）。杂合 MTHFR CT 基因型（rs1801133；OR，1.457）的比值比也显著升高。在 TP53（rs1042522）和 CYP2E1（rs3813867）中未发现显著相关性。此外，我们发现吸烟者的风险更高（OR，2.688），并确定妊娠是一个显著的风险因素（OR，1.54）。
我们的方案为进一步回顾性评估潜在遗传标记物提供了一种可行的方法。这项研究揭示了一种罕见 SNP 基因型与宫颈癌前病变的遗传关联，这是迄今为止最大的患者样本之一，值得进一步研究。
