Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstrasse 20, Ulm, Germany.
Pharmacogenomics J. 2013 Apr;13(2):181-8. doi: 10.1038/tpj.2011.51. Epub 2011 Dec 13.
The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment. A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling. Skin rash was absent in 26 (23.9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P=0.005). The EGFR polymorphisms, 497G/A (P=0.008), and the haplotypes of the promoter variants, EGFR-216G/T and -191C/A (P=0.029), were associated with the appearance of skin rash. In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P=0.045) and overall survival (P=0.009). In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.
本研究旨在探讨与表皮生长因子受体（EGFR）抑制剂治疗相关的皮疹的遗传决定因素。共对 109 例接受 EGFR 抑制剂首次治疗的前瞻性采样癌症患者进行了功能性 EGFR 多态性和参与受体下游信号的基因中的标记变体的基因分型。皮疹缺失的患者有 26 例（23.9%），与出现皮疹的患者相比，总体生存时间更短（P=0.005）。EGFR 多态性 497G/A（P=0.008）和启动子变异体 EGFR-216G/T 和-191C/A 的单倍型（P=0.029）与皮疹的出现有关。此外，PIK3CA 基因中的常见单倍型与皮疹（P=0.045）和总生存时间（P=0.009）相关。总之，EGFR 基因及其下游信号伙伴 PIK3CA 内的遗传变异可能预测 EGFR 抑制剂相关的皮疹。
