Saip R, Sen F, Vural B, Ugurel E, Demirkan A, Derin D, Eralp Y, Camlica H, Ustuner Z, Ozbek U
Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.
J BUON. 2011 Apr-Jun;16(2):241-6.
Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients.
Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves.
We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease.
No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.
肺癌治疗中许多常用的化疗药物由谷胱甘肽-S转移酶（GSTs）代谢。GST的胎盘同工型（GSTP1）是肺中最丰富的同工型。GSTP1内的多态性可能导致酶活性改变，并改变对铂类化疗的敏感性。我们研究了GSTP1基因第5和第6外显子内的多态性是否会改变小细胞肺癌（SCLC）患者的治疗反应、肿瘤进展时间（TTP）和总生存期。
1995年至2006年期间，94例经组织学确诊的SCLC患者纳入本研究。采用PCR-RFLP技术测定第5外显子的GSTP1 Ile105Val多态性和第6外显子的GSTP1 Ala-114Val多态性。使用卡方检验评估GSTP1多态性与治疗反应之间的关联。使用Kaplan-Meier生存曲线比较GSTP1多态性与TTP和总生存期之间的关联。
我们发现第5和第6外显子GSTP1基因多态性与治疗反应或总生存期之间无显著关联。同时携带第5外显子变异型（Ile/Val或Val/Val）和第6外显子变异型（Ala/Val）基因型的患者TTP显著缩短（5个月对8个月，p = 0.04）。此外，第6外显子杂合子变异型患者表现为广泛期疾病。
未发现变异等位基因对化疗反应、中位TTP和总生存期有个体影响。两种类型变异等位基因的携带可能预示着更差的预后。
