Very low prevalence of XPD K751Q polymorphism and its association with XPD expression and outcomes of FOLFOX-4 treatment in Asian patients with colorectal carcinoma

Jiun I. Lai, Cheng Hwai Tzeng, Po Min Chen, Jen Kou Lin, Tzu Chen Lin, Wei Shone Chen, Jeng Kae Jiang, Huann Sheng Wang, Wei Shu Wang*

*此作品的通信作者

研究成果: Article同行評審

32 引文 斯高帕斯(Scopus)

摘要

Xeroderma pigmentosum group D (XPD) participates in DNA unwinding during nucleotide excision repair, which may alter the efficacy of platinum-based chemotherapy. We analyzed the influence of codon 751 Lys→Gln polymorphism of XPD on its protein expression levels, clinico-pathological features, and outcome of 188 Chinese patients with metastatic colorectal carcinoma (CRC) that had been treated with first-line Oxaliplatin+Leucovorin+5-Fluorouracil (FOLFOX-4) chemotherapy. The results showed that in comparison with Caucasian populations, a remarkably lower prevalence of Lys/Gln genotype was noted (16%, n = 30). No between-group difference in XPD protein expression of patients with or without this polymorphism was noted (56.5% vs 59.7%; P = 0.783). Patients with Gln751 allele have a significantly lower response to FOLFOX-4 treatment (36.7% vs 58.2%, P = 0.03), and shorter progression-free (7. vs 11.months; P < 0.01) and overall (14. vs 22.months; P < 0.01) survivals. The incidence of grade 3/4 oxaliplatin-neuropathies was very similar in both groups (13.3% vs 16.5%; P = 0.67). By adjusted analysis, this polymorphism was further identified as an independent prognostic factor (P = 0.03). These data suggest that Asian populations have a significantly lower prevalence of codon 751 Lys/Gln polymorphism in XPD, which could be a key determinant for good response to oxaliplatin-based treatment and favorable outcomes.

原文English
頁(從 - 到)1261-1266
頁數6
期刊Cancer Science
100
發行號7
DOIs
出版狀態Published - 2009

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