DNA修复通路遗传变异和HPV感染转归与宫颈癌同步放化疗预后的分子流行病学研究

The prognosis of cervical cancer patients with similar clinical characteristics treated with the same concurrent chemoradiotherapy regimen varies a lot. Current studies suggested that the single nucleotide polymorphisms (SNPs) of DNA repair genes of the hosts are probably associated with the clinical responses to concurrent chemoradiotherapy of cervical cancer patients. On the other hand, human papillomavirus (HPV) infection and persistence might relate to the prognosis of cervical cancer patients. Hence, our study will focus on the interaction between genetic variations of DNA repair genes and HPV genotypes infection by case-case study design with the analyses as below: firstly, to analyze the associations between 51 potential functional SNPs of 23 key genes and response to concurrent chemoradiotherapy systematically by taking the pathway as a unit, and demonstrate the underline mechanism by phenotype detection and function assessment. Secondly, considering the correlation between HPV genotypes infection and persistence and prognosis of cervical cancer, to evaluate its interaction with genetic variations of DNA repair genes to the prognosis by bio-statistical methods comprehensively. Finally, to establish the prognostic prediction model for cervical cancer patients with concurrent chemoradiotherapy with multi-factors and genetic biomarkers. This study will provide scientific basis for the screening of stable biomarkers, prediction of individual response and prognosis, and consequent application of personalized therapy.

临床分期相同的宫颈癌患者接受同样的同步放化疗方案，效果常相差很大。已有研究提示:DNA修复基因单核苷酸多态性(Single nucleotide polymorphisms,SNPs)可能与个体放化疗敏感性密切相关，而人乳头状瘤病毒(Human papillomavirus, HPV)感染亚型及转归也会影响预后。因此本研究拟采用病例-病例研究设计，以DNA修复基因SNPs和HPV感染亚型交互作用为核心，以通路为单位，系统分析23个主要基因51个功能性SNPs与个体放化疗敏感性的关系，并通过表型和功能学实验探索其生物学机制；同时结合HPV感染亚型及转归情况，综合评价遗传变异与HPV感染亚型对宫颈癌放化疗预后交互作用的方式和强度，最终建立包括多因素多遗传标记在内的宫颈癌同步放化疗预后预测模型。研究结果将对筛选稳定的生物标志物，预测个体放化疗敏感性及预后，从而实现有效的个体化治疗提供科学依据。

临床分期相同的宫颈癌患者接受同样的同步放化疗方案，效果常相差很大。DNA修复通路不同基因多态性可能与宫颈癌同步放化疗敏感性、预后密切相关，而人乳头状瘤病毒 (Human papillomavirus, HPV)感染亚型及转归也会影响预后。本研究采用病例-病例研究设计 (Case-case study)，以DNA修复基因单核苷酸多态性(Single nucleotide polymorphisms, SNPs)和HPV感染亚型为核心，以通路为单位，系统分析了26个主要基因合计58个功能性SNPs与个体放化疗敏感性的关联，并通过表型和功能学实验探索其生物学机制；同时，系统评价HPV感染亚型和变异体对宫颈癌同步放化疗预后作用的方式和强度。研究结果发现HPV感染亚型影响宫颈癌同步放化疗的敏感性和预后转归情况。研究结果对筛选稳定的生物标志物，预测个体放化疗敏感性及预后，从而制定有效且目标明确的宫颈癌个体化治疗方案，提高患者的生存质量及延长生存时间，提供了新的科学依据和线索，具有重要的科学理论意义和临床实践应用价值。