Cyclin D1 gene (CCND1) polymorphism and the risk of squamous cell carcinoma of the larynx.

Cyclin D1 is one of the key proteins involved in cell cycle control, and it is believed that its overexpression may be connected with tumorigenesis. A reason for cyclin D1 deregulation may be connected to a common G870A polymorphism at codon 242 in exon 4 of the CCND1 gene. This single nucleotide substitution, localized in the conserved splice donor site between exon 4 and the intron 4 boundary, might modulate the frequency of alternative splicing. It has been postulated that the A allele results in a higher level of mRNA (transcript b) encoding a protein with an altered C-terminal domain. The influence of CCND1 G-->A polymorphism for the risk of cancer and the prognosis of patients with different types of solid tumors has already been suggested. This study was conducted to investigate the association between the cyclin D1 gene polymorphism and laryngeal cancer risk, as well as the clinical outcome. We also examined the relationship between genotype/allele distributions and the cyclin D1 expression profile. The genotyping study was done using the PCR-RFLP method in 63 patients with larynx cancer and 102 healthy controls. The heterozygotic genotype GA as well as a combination of GA and AA genotypes were associated with an increased risk of larynx cancer compared to the GG genotype (OR =3.02; P =0.004 and OR =2.52; P =0.013, respectively). The A allele frequency was higher in cancer cases (0.484) than in controls (0.416) that were connected with a slightly increased risk of cancer development (OR =1.34); however, the difference was not significant. The AA genotype was associated with an early cancer onset compared to the GG genotype (median age: 51.5 and 63.0 years, respectively). We also demonstrated that the AA genotype was associated with the occurrence of lymph node metastases (OR =3.26) and a higher level of cyclin D1 overexpression. These results suggest that the CCND1 A allele may be a genetic factor that modulates the risk of larynx cancer development, and it may also have an effect on tumor biology and disease prognosis.