期刊
PHARMACOGENOMICS JOURNAL
卷 14, 期 3, 页码 256-262出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2013.29
关键词
amphiregulin; anti-EGFR; colorectal cancer; EGFR pathway; intergenic; polymorphisms
资金
- Instituto de Salud Carlos III [FIS/1101711, CM11/00102]
In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using Hap Map database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C >A, rs13104811 A> G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall Survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS. Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.
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