Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy

Jeong Seon Ryu, Yun-Chul Hong, Hye Seung Han, Jong Eun Lee, Sook Kim, Young Mee Park, Young Chul Kim, Tae Sook Hwang

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C→T), XPD Lys751Gln (A→C) and Asp312Asn (G→A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95% CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95% CI, 333-x), which was significantly different from the 281 days (95% CI, 214-376) of patients with the variant genotype (T/T or C/T) (P=0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P=0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P=0.4711and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.

Original languageEnglish
Pages (from-to)311-316
Number of pages6
JournalLung Cancer
Volume44
Issue number3
DOIs
StatePublished - 1 Jun 2004

Fingerprint

Combination Drug Therapy
Non-Small Cell Lung Carcinoma
DNA Repair
Cisplatin
Survival
Codon
Genotype
Drug Therapy
Genes
Proportional Hazards Models
Weight Loss
Survival Rate
Biomarkers

Keywords

  • ERCC1
  • Non-small-cell lung cancer
  • Nucleotide excision repair
  • XPD/ERCC2

Cite this

Ryu, Jeong Seon ; Hong, Yun-Chul ; Han, Hye Seung ; Lee, Jong Eun ; Kim, Sook ; Park, Young Mee ; Kim, Young Chul ; Hwang, Tae Sook. / Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. In: Lung Cancer. 2004 ; Vol. 44, No. 3. pp. 311-316.
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abstract = "ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C→T), XPD Lys751Gln (A→C) and Asp312Asn (G→A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95{\%} CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95{\%} CI, 333-x), which was significantly different from the 281 days (95{\%} CI, 214-376) of patients with the variant genotype (T/T or C/T) (P=0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P=0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P=0.4711and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.",
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Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. / Ryu, Jeong Seon; Hong, Yun-Chul; Han, Hye Seung; Lee, Jong Eun; Kim, Sook; Park, Young Mee; Kim, Young Chul; Hwang, Tae Sook.

In: Lung Cancer, Vol. 44, No. 3, 01.06.2004, p. 311-316.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy

AU - Ryu, Jeong Seon

AU - Hong, Yun-Chul

AU - Han, Hye Seung

AU - Lee, Jong Eun

AU - Kim, Sook

AU - Park, Young Mee

AU - Kim, Young Chul

AU - Hwang, Tae Sook

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