Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients

Tomoyoshi Takenaka, Tokujiro Yano, Chikako Kiyohara, Naoko Miura, Hidenori Kouso, Taro Ohba, Takuro Kometani, Fumihiro Shoji, Ichiro Yoshino, Yoshihiko Maehara

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Abstract

Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. Method: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. Result: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45%, 48% and 7%, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70% and 30%, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p = 0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. Conclusion: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalLung Cancer
Volume67
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

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Non-Small Cell Lung Carcinoma
DNA Repair
Single Nucleotide Polymorphism
Platinum
Genotype
Survival
Disease-Free Survival
Drug Therapy
Proteins
Carcinogenesis
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients. / Takenaka, Tomoyoshi; Yano, Tokujiro; Kiyohara, Chikako; Miura, Naoko; Kouso, Hidenori; Ohba, Taro; Kometani, Takuro; Shoji, Fumihiro; Yoshino, Ichiro; Maehara, Yoshihiko.

In: Lung Cancer, Vol. 67, No. 1, 01.01.2010, p. 101-107.

Research output: Contribution to journalArticle

Takenaka, Tomoyoshi ; Yano, Tokujiro ; Kiyohara, Chikako ; Miura, Naoko ; Kouso, Hidenori ; Ohba, Taro ; Kometani, Takuro ; Shoji, Fumihiro ; Yoshino, Ichiro ; Maehara, Yoshihiko. / Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients. In: Lung Cancer. 2010 ; Vol. 67, No. 1. pp. 101-107.
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abstract = "Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. Method: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. Result: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45{\%}, 48{\%} and 7{\%}, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70{\%} and 30{\%}, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p = 0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. Conclusion: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.",
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T1 - Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients

AU - Takenaka, Tomoyoshi

AU - Yano, Tokujiro

AU - Kiyohara, Chikako

AU - Miura, Naoko

AU - Kouso, Hidenori

AU - Ohba, Taro

AU - Kometani, Takuro

AU - Shoji, Fumihiro

AU - Yoshino, Ichiro

AU - Maehara, Yoshihiko

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. Method: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. Result: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45%, 48% and 7%, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70% and 30%, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p = 0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. Conclusion: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.

AB - Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. Method: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. Result: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45%, 48% and 7%, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70% and 30%, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p = 0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. Conclusion: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.

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