ERCC1 and ERCC2 variants predict survival in gastric cancer patients.

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Date

2013-01

Authors

Li, Yangkai
Liu, Zhensheng
Liu, Hongliang
Wang, Li-E
Tan, Dongfeng
Ajani, Jaffer A
Wei, Qing-Yi

Editors

Miao, Xiaoping

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Abstract

PURPOSE: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients. EXPERIMENTAL DESIGN: We genotyped by the TaqMan assay three common, potentially functional ERCC1 (rs3212986) and ERCC2 SNPs (rs13181 and rs1799793) in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes. RESULTS: We found that, compared with ERCC2 rs1799793 GG+AG genotypes, the homozygous variant AA genotype was associated with significantly poorer overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56; P=0.004). In combined analyses, patients with any one of the three unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA) had statistically significant hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025), compared with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986) had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011), compared with the common haplotype G-T-G. CONCLUSION: ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective studies are essential to confirm our findings.

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Humans, Stomach Neoplasms, Endonucleases, DNA-Binding Proteins, Proportional Hazards Models, Haplotypes, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Xeroderma Pigmentosum Group D Protein, Young Adult

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0071994

Publication Info

Li, Yangkai, Zhensheng Liu, Hongliang Liu, Li-E Wang, Dongfeng Tan, Jaffer A Ajani and Qing-Yi Wei (2013). ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PloS one, 8(9). p. e71994. 10.1371/journal.pone.0071994 Retrieved from https://hdl.handle.net/10161/18022.

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