Tumor Site- and Stage-Specific Associations between Allelic Variants of Glutathione S-Transferase and DNA-Repair Genes and Overall Survival in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Chemotherapy

Ching Yu Lai, Ling Ling Hsieh, Fung Chang Sung, Reiping Tang, Chyi Huey Bai, Fang Yang Wu, Hung Yi Chiou, Chih Ching Yeh

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

Introduction:Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.Material and Methods:We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.Results:The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR = 1.38, 95% CI = 1.02-1.87), and rectal cancer patients had the poorest survival among them (HR = 1.87, 95% CI = 1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR = 1.69, 95% CI = 1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR = 2.60, 95% CI = 1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR = 2.77, 95% CI = 1.25-6.17).Conclusion:The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.

原文英語
文章編號e69039
期刊PLoS One
8
發行號7
DOIs
出版狀態已發佈 - 七月 23 2013

指紋

fluorouracil
Chemotherapy
DNA repair
Glutathione Transferase
colorectal neoplasms
glutathione transferase
Fluorouracil
DNA Repair
drug therapy
Tumors
Colorectal Neoplasms
Hazards
Repair
Genes
Drug Therapy
neoplasms
Survival
DNA
confidence interval
Confidence Intervals

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

引用此文

@article{e3d7569fc2b14fc58ac00a4ba07a8b08,
title = "Tumor Site- and Stage-Specific Associations between Allelic Variants of Glutathione S-Transferase and DNA-Repair Genes and Overall Survival in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Chemotherapy",
abstract = "Introduction:Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.Material and Methods:We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95{\%} confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.Results:The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR = 1.38, 95{\%} CI = 1.02-1.87), and rectal cancer patients had the poorest survival among them (HR = 1.87, 95{\%} CI = 1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR = 1.69, 95{\%} CI = 1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR = 2.60, 95{\%} CI = 1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR = 2.77, 95{\%} CI = 1.25-6.17).Conclusion:The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.",
author = "Lai, {Ching Yu} and Hsieh, {Ling Ling} and Sung, {Fung Chang} and Reiping Tang and Bai, {Chyi Huey} and Wu, {Fang Yang} and Chiou, {Hung Yi} and Yeh, {Chih Ching}",
year = "2013",
month = "7",
day = "23",
doi = "10.1371/journal.pone.0069039",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

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TY - JOUR

T1 - Tumor Site- and Stage-Specific Associations between Allelic Variants of Glutathione S-Transferase and DNA-Repair Genes and Overall Survival in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Chemotherapy

AU - Lai, Ching Yu

AU - Hsieh, Ling Ling

AU - Sung, Fung Chang

AU - Tang, Reiping

AU - Bai, Chyi Huey

AU - Wu, Fang Yang

AU - Chiou, Hung Yi

AU - Yeh, Chih Ching

PY - 2013/7/23

Y1 - 2013/7/23

N2 - Introduction:Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.Material and Methods:We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.Results:The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR = 1.38, 95% CI = 1.02-1.87), and rectal cancer patients had the poorest survival among them (HR = 1.87, 95% CI = 1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR = 1.69, 95% CI = 1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR = 2.60, 95% CI = 1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR = 2.77, 95% CI = 1.25-6.17).Conclusion:The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.

AB - Introduction:Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.Material and Methods:We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.Results:The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR = 1.38, 95% CI = 1.02-1.87), and rectal cancer patients had the poorest survival among them (HR = 1.87, 95% CI = 1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR = 1.69, 95% CI = 1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR = 2.60, 95% CI = 1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR = 2.77, 95% CI = 1.25-6.17).Conclusion:The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.

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