ERCC基因多态性与骨肉瘤的生存相关性

目的探讨骨肉瘤患者及正常人群 (excision repair cross-complementing, ERCC) 基因ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2Lys751Gln (rs13181) 单核苷酸多态性与骨肉瘤患者对顺铂的反应和生存状况的关系.方法 2011年1月至2015年12月住院收治的骨肉瘤患者161例及正常人群163例, 静脉血2 m L, 用实时逆转录聚合酶链式反应方法 (real time quantitative polymerase chain reaction, RT-PCR) 比较骨肉瘤患者及正常人群ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2 Lys751Gln (rs13181) 基因型及等位基因分布频率.对骨肉瘤患者按不同的临床因素 (年龄、性别、病理类型、肿瘤部位、Enneking外科分期、肿瘤转移及治疗方法) 进行分组, 比较各组基因型频率及等位基因频率, 分析基因多态性与各临床因素的关系.结果 (1) ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2Lys751Gln (rs13181) 基因型有CC、CT、TT型, 骨肉瘤患者及正常人群基因型频率 (CC、CT、TT) 及等位基因频率 (C、T) 比较差异均无统计学意义 (P=0.590, P=0.544) ; (2) 对于ERCC1 Asn118Asn, 与野生型C/C相比, 突变型T/T与较高的无病生存率显著相关, 校正OR值 (95%CI) 0.37 (0.150.85) .ERCC2 751 A/A基因型表现为骨肉瘤患者生存率增加 (HR=0.45, 95%CI 0.110.88) .没有证明ERCC1 Gln504Lys与ERCC2Asp312Asn的多态性和骨肉瘤预后相关.结论 ERCC基因ERCC1 Asn118Asn118T/T和ERCC2 Lys751Gln A/A多态性与骨肉瘤无病生存率 (SFS) 相关, 可以用作顺铂治疗的骨肉瘤患者临床预后的标志物.而ERCC1 Gln504Lys (rs3212986) 、ERCC2 Asp312Asn与骨肉瘤无病生存率 (SFS) 无相关性.

Relationship between Single Nucleotide Polymorphisms of ERCC Gene and Survival of Osteosarcoma

Objective To study the relationship between single nucleotide polymorphisms (SNPs) of ERCC1 Asn118 Asn (rs11615) , ERCC1 Gln504 Lys (rs3212986) , ERCC2 Asp312 Asn (rs1799793) and ERCC2 Lys751 Gln (rs13181) and osteosarcoma survival with the osteosarcoma patients.Methods 161 patients with osteosarcoma in our hospital from January 2010 to Decemher 2015 and 163 heahhy adults were enrolled in this study.2 m L peripheral blood samples were taken from each person.The RT-q PCR method was used to detect the genotype and allele frequency distribution of ERCC1 Asn118 Asn (rs11615) , ERCC1 Gln504 Lys (rs3212986) , ERCC2 Asp312 Asn (rs1799793) and ERCC2 Lys751 Gln (rs13181) in osteosarcoma patients and normal population.Osteosarcoma patients were divided into several groups according to the clinical parameters such as age, gender, histology, tumor location, Enneking classification, tumormetastasis and therapy, and analyzed the relations between the genetic polymorphism and clinical parameters.Results For ERCC1 Asn118 Asn, thevariant genotype T/T was strongly significantly associated with a higher disease-free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.37 (0.15-0.85) .ERCC2 751 A/A genotype showed increased disease-free survival of osteosarcoma (HR=0.45; 95% CI=0.11-0.88) .However, we did not find significant association of ERCC1 Gln504 Lys and ERCC2 Asp312 Asn polymorphisms with prognosis of osteosarcoma.Conclusions The genetic polymorphism of ERCC gene at ERCC1 Asn118 Asn T/T, ERCC2 Lys751 Gln A/A is associated with osteosarcoma disease-free survival (SFS) , can be used as clinical prognostic markers for osteosarcoma patients with cisplatin treatment.But ERCC1 Gln504 Lys (rs3212986) , ERCC2 Asp312 Asn have no correlation with osteosarcoma disease-free survival (SFS) .