Association between CCND1 G/A870 Polymorphism, Allele-Specific Amplification, Cyclin D1 Expression, and Survival in Esophageal and Lung Carcinoma

• Published in: Clinical cancer research 2008-12, Vol.14 (23), p.7804-7812
• Main Authors: Gupta, Vanita K, Feber, Andrew, Xi, Liqiang, Pennathur, Arjun, Wu, Maoxin, Luketich, James D, Godfrey, Tony E
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adult; Aged; Aged, 80 and over; Alleles; Antineoplastic agents; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; CCND1; cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; esophageal adenocarcinoma; Esophageal Neoplasms - genetics; Esophageal Neoplasms - mortality; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Amplification; Gene Expression; Genotype; Humans; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; NSCLC; Pharmacology. Drug treatments; Pneumology; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Protein Isoforms - genetics; Protein Isoforms - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0744

Purpose: Cyclin D1 is found on 11q13, which is a region frequently amplified in several tumor types. The CCND1 locus gives rise to at least two protein isoforms of D1 (D1a and D1b). A common G/A polymorphism (G/A870) is thought to influence the expression levels of D1a and D1b. D1b has been suggested to be increased in the presence of the A allele and more oncogenic than D1a. Furthermore, the A allele has been reported to correlate with increased risk of carcinoma in several tumor types, suggesting that this polymorphism and D1b are important in tumor progression. However, contradictory data about the polymorphism, D1 variant expression, and correlation with survival have been reported. We explored the relationship between gene amplification, G/A870 genotype, D1a and D1b expression, and overall survival in esophageal adenocarcinoma and non–small cell lung cancer. Experimental Design: DNA and RNA were isolated from 54 esophageal adenocarcinoma samples and 89 non–small cell lung cancer samples and were analyzed for gene amplification, genotype at the polymorphism, gene expression, and association with overall survival. Results: The D1 variant expression did not correlate with amplification, genotype, or overall survival in either tumor type. The total D1 expression correlated with decreased patient survival. Several other genes on 11q13 also seem to be overexpressed and correlated with decreased survival. Conclusions: We report that the G/A870 polymorphism does not correlate with patient survival, or with D1a or D1b expression. However, the total D1 expression and the expression of several other genes on 11q13 seem to be associated with esophageal adenocarcinoma patient survival.