XRCC1基因精氨酸194位突变为色氨酸以及GGH基因-401位点胞嘧啶/胸腺嘧啶多态性与宫颈癌铂类新辅助化疗疗效相关。

XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer.

作者信息

Kim Kidong, Kang Soon-Beom, Chung Hyun Hoon, Kim Jae Weon, Park Noh-Hyun, Song Yong-Sang

机构信息

Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.

出版信息

Gynecol Oncol. 2008 Dec;111(3):509-15. doi: 10.1016/j.ygyno.2008.08.034. Epub 2008 Oct 12.

DOI:10.1016/j.ygyno.2008.08.034

PMID:18851872

Abstract

OBJECTIVE

The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of genes which are involved in DNA synthesis and repair with the response to platinum-based neoadjuvant chemotherapy (NAC) and disease-free survival (DFS) in patients with cervical cancer who were treated with NAC followed by radical hysterectomy.

METHODS

A retrospective review was performed on 66 patients with cervical cancer who were treated with NAC followed by radical hysterectomy in our institute between January 1999 and February 2007. DNA was extracted from the paraffin-embedded, formalin-fixed tissue blocks of hysterectomy specimens. The genotypes of SNPs (MTHFR 677Cytosine/Thymine, XRCC1 Arginine194Tryptophan, GGH-401Cytosine/Thymine, and GSTP1 Isoleucine105Valine) were determined using a single base primer extension assay. The association of SNP genotypes with the response to NAC, which was measured by physical and colposcopic examinations, was evaluated. In addition, DFS based on SNP genotypes was examined.

RESULTS

The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.023 for XRCC1 Arginine194Tryptophan; P=0.046 for GGH-401Cytosine/Thymine). However, the genotypes of MTHFR 677Cytosine/Thymine and GSTP1 Isoleucine105Valine were not associated with the response to NAC. In subgroup analysis with 39 patients who were treated with regimens containing 5-fluorouracil (5-FU), the genotypes of GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.039). In multifactor dimensionality reduction (MDR) analysis, the combination of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine genotypes was associated with the response to NAC (P<0.001). However, no SNP genotypes were associated with DFS, but the cisplatin dose intensity of NAC was associated with DFS.

CONCLUSIONS

The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were associated with the response to NAC in patients with cervical cancer. However, no SNP genotypes were associated with DFS.

摘要

目的

本研究的目的是评估参与DNA合成与修复的基因单核苷酸多态性（SNP）与接受铂类新辅助化疗（NAC）后行根治性子宫切除术的宫颈癌患者对NAC的反应及无病生存期（DFS）之间的关联。

方法

对1999年1月至2007年2月在我院接受NAC后行根治性子宫切除术的66例宫颈癌患者进行回顾性研究。从子宫切除标本的石蜡包埋、福尔马林固定组织块中提取DNA。使用单碱基引物延伸分析确定SNP（亚甲基四氢叶酸还原酶677胞嘧啶/胸腺嘧啶、X线修复交叉互补蛋白1精氨酸194色氨酸、γ-谷氨酰转肽酶-401胞嘧啶/胸腺嘧啶和谷胱甘肽S-转移酶P1异亮氨酸105缬氨酸）的基因型。评估SNP基因型与通过体格检查和阴道镜检查测量的NAC反应之间的关联。此外，还检查了基于SNP基因型的DFS。

结果

X线修复交叉互补蛋白1精氨酸194色氨酸和γ-谷氨酰转肽酶-401胞嘧啶/胸腺嘧啶的基因型与NAC反应显著相关（X线修复交叉互补蛋白1精氨酸194色氨酸，P = 0.023；γ-谷氨酰转肽酶-401胞嘧啶/胸腺嘧啶，P = 0.046）。然而，亚甲基四氢叶酸还原酶677胞嘧啶/胸腺嘧啶和谷胱甘肽S-转移酶P1异亮氨酸105缬氨酸的基因型与NAC反应无关。在对39例接受含5-氟尿嘧啶（5-FU）方案治疗的患者进行的亚组分析中，γ-谷氨酰转肽酶-401胞嘧啶/胸腺嘧啶的基因型与NAC反应显著相关（P = 0.039）。在多因素降维（MDR）分析中，X线修复交叉互补蛋白1精氨酸194色氨酸和γ-谷氨酰转肽酶-401胞嘧啶/胸腺嘧啶基因型的组合与NAC反应相关（P < 0.001）。然而，没有SNP基因型与DFS相关，但NAC的顺铂剂量强度与DFS相关。