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ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

BACKGROUND: Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that...

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Autores principales: Huang, Ming-Yii, Fang, Wei-Yu, Lee, Su-Chen, Cheng, Tian-Lu, Wang, Jaw-Yuan, Lin, Shiu-Ru
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262891/
https://www.ncbi.nlm.nih.gov/pubmed/18267032
http://dx.doi.org/10.1186/1471-2407-8-50
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author Huang, Ming-Yii
Fang, Wei-Yu
Lee, Su-Chen
Cheng, Tian-Lu
Wang, Jaw-Yuan
Lin, Shiu-Ru
author_facet Huang, Ming-Yii
Fang, Wei-Yu
Lee, Su-Chen
Cheng, Tian-Lu
Wang, Jaw-Yuan
Lin, Shiu-Ru
author_sort Huang, Ming-Yii
collection PubMed
description BACKGROUND: Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes. METHODS: Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R) or triple (3R) tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0) or III (any T N1 and 2 M0) and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU) and leucovorin (LV). The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated. RESULTS: In this study, the distributions of GSTP1 (P = 0.003), ABCB1 (P = 0.001), TYMS (P < 0.0001), ERCC2 (P < 0.0001) and XRCC1 (P = 0.006) genotypes in the Asian population, with the exception of MTHFR (P = 0.081), differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006), tumor invasion depth (P = 0.025), lymph node metastasis (P = 0.011) and cancer stage (P = 0.008) were significantly correlated with early relapse. Patients carrying the ERCC2 2251AC or2251CC genotypes had a significantly increased risk of early relapse (OR = 3.294, 95% CI, 1.272–8.532). CONCLUSION: We suggest that ERCC2 2251A>C alleles may be genetic predictors of early CRC relapse.
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spelling pubmed-22628912008-03-05 ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study Huang, Ming-Yii Fang, Wei-Yu Lee, Su-Chen Cheng, Tian-Lu Wang, Jaw-Yuan Lin, Shiu-Ru BMC Cancer Research Article BACKGROUND: Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes. METHODS: Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R) or triple (3R) tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0) or III (any T N1 and 2 M0) and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU) and leucovorin (LV). The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated. RESULTS: In this study, the distributions of GSTP1 (P = 0.003), ABCB1 (P = 0.001), TYMS (P < 0.0001), ERCC2 (P < 0.0001) and XRCC1 (P = 0.006) genotypes in the Asian population, with the exception of MTHFR (P = 0.081), differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006), tumor invasion depth (P = 0.025), lymph node metastasis (P = 0.011) and cancer stage (P = 0.008) were significantly correlated with early relapse. Patients carrying the ERCC2 2251AC or2251CC genotypes had a significantly increased risk of early relapse (OR = 3.294, 95% CI, 1.272–8.532). CONCLUSION: We suggest that ERCC2 2251A>C alleles may be genetic predictors of early CRC relapse. BioMed Central 2008-02-12 /pmc/articles/PMC2262891/ /pubmed/18267032 http://dx.doi.org/10.1186/1471-2407-8-50 Text en Copyright © 2008 Huang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Ming-Yii
Fang, Wei-Yu
Lee, Su-Chen
Cheng, Tian-Lu
Wang, Jaw-Yuan
Lin, Shiu-Ru
ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title_full ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title_fullStr ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title_full_unstemmed ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title_short ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
title_sort ercc2 2251a>c genetic polymorphism was highly correlated with early relapse in high-risk stage ii and stage iii colorectal cancer patients: a preliminary study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262891/
https://www.ncbi.nlm.nih.gov/pubmed/18267032
http://dx.doi.org/10.1186/1471-2407-8-50
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