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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.

SUBMITTER: Lai CY 

PROVIDER: S-EPMC3720885 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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.

Lai Ching-Yu CY   Hsieh Ling-Ling LL   Sung Fung-Chang FC   Tang Reiping R   Bai Chyi-Huey CH   Wu Fang-Yang FY   Chiou Hung-Yi HY   Yeh Chih-Ching CC  

PloS one 20130723 7


<h4>Introduction</h4>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.<h4>Material and methods</h4>We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-haz  ...[more]

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