TY - JOUR
T1 - Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
AU - Carcereny, Enric
AU - Ramirez, Jose Luis
AU - Sanchez-Ronco, Maria
AU - Isla, Dolores
AU - Cobo, Manuel
AU - Moran, Teresa
AU - de Aguirre, Itziar
AU - Okamoto, Tatsuro
AU - Wei, Jia
AU - Provencio, Mariano
AU - Lopez-Vivanco, Guillermo
AU - Camps, Carlos
AU - Domine, Manuel
AU - Alberola, Vicente
AU - Sanchez, Jose Miguel
AU - Massuti, Bartomeu
AU - Mendez, Pedro
AU - Taron, Miquel
AU - Rosell, Rafael
N1 - Funding Information:
This study was partially supported by a grant from the National Cancer Institute (NCI; 5U01CA114771-02 ), by a grant from the Spanish Ministry of Science and Innovation , Redes Temáticas de Investigación Cooperativa en Cáncer (RTICC; RD06/0020/0056 ), and by La Fundación Badalona Contra el Cáncer . None of the funding agencies were involved in the design and conduct, data management and analysis, manuscript preparation and review, or decision to submit.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.lungcan.2009.08.004
DO - 10.1016/j.lungcan.2009.08.004
M3 - Article
C2 - 19733931
AN - SCOPUS:77952553157
SN - 0169-5002
VL - 68
SP - 491
EP - 497
JO - Lung Cancer
JF - Lung Cancer
IS - 3
ER -
