کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2142557 1088320 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
چکیده انگلیسی
Nicotine acetylcholine receptors (nAChRs) are associated with resistance to gemcitabine, cisplatin and paclitaxel in non-small-cell lung cancer (NSCLC) cell lines. Three single nucleotide polymorphisms (SNPs) of CHRNA3, CHRNA5 and LOC123688 increase lung cancer risk. These SNPs may have influenced outcome in patients treated in our phase III trial. Stage IV NSCLC patients were treated with customized chemotherapy based on ERCC1 (excision repair cross-complementing 1) mRNA expression. Patients in the control arm received docetaxel/cisplatin; patients in the genotypic arm with low levels of ERCC1 received docetaxel/cisplatin; patients in the genotypic arm with high levels of ERCC1 received docetaxel/gemcitabine. DNA was extracted from lymphocytes, and CHRNA3 (rs1051730), CHRNA5 (rs16969968) and LOC123688 (rs8034191) SNPs were genotyped with the Taqman allele discrimination assay. A significant interaction was found for CHRNA3 and PS (P = 0.02). In patients with PS 0, CT patients had a better response than both CC (P = 0.01) and TT (P = 0.02) patients, and patients in the low genotypic group also had a better response (P = 0.01). When the CHRNA3 genotype was added in the multivariate analysis for progression-free survival, an improvement was observed in the low genotypic group in PS 0 patients (P = 0.02). PS 0 patients in the low genotypic group with the CT genotype attained an 84% response rate, 12.1-month progression-free survival, and 19-month median survival. CHRNA3 (rs1051730) genotyping can improve customized chemotherapy based on tumor assessment of ERCC1 mRNA in stage IV NSCLC with PS 0.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 68, Issue 3, June 2010, Pages 491-497
نویسندگان
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