Journal Article

Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case–control study

Yuxin Zheng, Hongbing Shen, Erich M. Sturgis, Li-E Wang, Susan A. Eicher, Sara S. Strom, Marsha L. Frazier, Margaret R. Spitz and Qingyi Wei

in Carcinogenesis

Volume 22, issue 8, pages 1195-1199
Published in print August 2001 | ISSN: 0143-3334
Published online August 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.8.1195
Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case–control study

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  • Clinical Cytogenetics and Molecular Genetics

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A G→A polymorphism (G870A) in exon 4 of the cyclin D1 (CCND1) gene creates an alternative splice site in its mRNA, encoding a protein with an altered C-terminal domain. It has been suggested that DNA damage in cells with the A allele bypasses the G1/S checkpoint of the cell cycle more easily than damage in cells without the A allele. Because CCND1 plays a critical role in cell cycle control and reduced DNA repair capacity is associated with an increased risk for squamous cell carcinoma of the head and neck (SCCHN), we hypothesize that this CCND1 polymorphism modulates individual susceptibility to SCCHN. To test this hypothesis we evaluated the frequency of the polymorphism in a hospital-based case–control study of 233 newly diagnosed SCCHN patients and 248 non-cancer controls. The cases and controls were frequency matched by age (±5 years), sex and tobacco use. All subjects were non-Hispanic whites. We found that the A allele frequency was slightly higher in the cases (0.485) than in the controls (0.425), but the difference was borderline statistically significant (P = 0.064). The frequencies of the CCND1 AA, GA and GG genotypes were 23.6, 49.8 and 26.6%, respectively, in cases and 16.5, 52.5 and 31.5%, respectively, in controls. Multivariate logistic regression analysis adjusting for age (in years), sex, smoking and alcohol use was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Compared with the wild-type CCND1 GG, the CCND1 A G genotype was associated with a non-significantly increased risk (adjusted OR 1.15, 95% CI 0.75–1.76), but the CCND1 AA genotype was associated with a significantly increased risk (adjusted OR 1.77, 95% CI 1.04–3.02) for SCCHN. Results from a trend test using a logistic regression model were statistically significant (P = 0.044). Among the cases the mean age of onset was 59.0, 56.8 and 55.5 years for the GG, GA and AA genotypes, respectively. In the stratification analysis the CCND1 AA variant genotype was associated with a >3-fold increased risk in individuals who were ≤50 years old (OR 3.18, 95% CI 1.19–8.46), females (3.57, 1.26–10.0), non-smokers (3.71, 1.37–10.1) and non-alcohol users (4.76, 1.61–14.0). These results suggest that the CCND1 polymorphism is associated with early onset of SCCHN and contributes to susceptibility to SCCHN in this population.

Keywords: CCND1, cyclin D1; CDK, cyclin-dependent kinase; CI, confidence interval; OR, odds ratio; SCCHN, squamous cell carcinoma of the head and neck; SSCP, single-strand conformation polymorphism.

Journal Article.  4084 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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