Cyclin D1 ( CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients

The cyclin D1 ( CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I–IV. CCND1 A870G genotype w...

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Vydané v:Lung cancer (Amsterdam, Netherlands) Ročník 51; číslo 3; s. 303 - 311
Hlavní autori: Gautschi, Oliver, Hugli, Barbara, Ziegler, Annemarie, Bigosch, Colette, Bowers, Naomi L., Ratschiller, Daniel, Jermann, Monika, Stahel, Rolf A., Heighway, Jim, Betticher, Daniel C.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Shannon Elsevier Ireland Ltd 01.03.2006
Elsevier Science
Predmet:
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Case-Control Studies
Chemotherapy
Cisplatin - administration & dosage
Cyclin D1
Cyclin D1 - genetics
Female
Gene polymorphism
Genetic Predisposition to Disease
Genotype
Humans
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Male
Medical sciences
Middle Aged
Neoplasm Staging
Pneumology
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Predictive factor
Smoking
Smoking - adverse effects
Statistics, Nonparametric
Survival Analysis
Tobacco, tobacco smoking
Toxicology
Tumors of the respiratory system and mediastinum
Chemotherapy
CCND1
NSCLC
Lung cancer
Cyclin D1
Predictive factor
Gene polymorphism
PCR
RFLP
Smoking
Human
Lung disease
Respiratory disease
Tobacco smoking
Risk
Malignant tumor
non-small cell lung carcinoma
Cisplatin
Treatment
Gene
Platinum
Risk factor
Carboplatin
Bronchus disease
Non small cell carcinoma
Polymorphism
ISSN:0169-5002, 1872-8332
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Shrnutí:The cyclin D1 ( CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I–IV. CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III–IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (≥40 py, P = 0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes ( P = 0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy ( P = 0.04). Survival analysis revealed no significant differences among the genotypes. Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2005.10.025