Cyclin D1 polymorphism and expression in patients with squamous cell carcinoma of the head and neck

We have previously reported that the cyclin DI (CCND1) GG(870) genotype was associated with poorly differentiated tumors and reduced disease-free inte rval in patients with squamous cell carcinoma of the head and neck (SCCHN). We have now examined the association of this and a second CCND1 polymorphi sm with gene expression and outcome in SCCHN patients. Analysis of a CCND1 G/C-1722 polymorphism revealed that CCND1 CC1722 genotype was associated wi th poorly differentiated tumors [P = 0.005; odds ratio (OR), 5.7; 95% CI, 1 .7 to 19.2), and reduced disease-free interval (P = 0.003; Hazard Ratio (HR ), 7.3; 95% Cl, 1.1 to 27.2.) independently from the influence of CCND1 GG( 870) genotype. Patients whose tumors were negative for cyclin D1 were assoc iated with reduced disease-free interval (P = 0.028; HR, 4.1; 95% CI, 1.4 t o 14.2). Although G/C-1722 genotypes were not associated with expression, w e found a significant trend between reduced expression of cyclin DI in pati ents with the CCND1 GG(870) genotype (P = 0.04). Splicing of CCND1 mRNA in head and neck tissues was modulated by CCND1 A/G(870) alleles, thus CCND1 t ranscript a was spliced equally from CCND1 A(870) and G(870) alleles, where as CCND1 transcript b was spliced mainly from the CCND1 A(870) allele. our analysis has also identified differences in cyclin D1 genotype and protein expression and the pathogenesis of SCCHN in males and females. Thus, CCND1 CC1722 genotype was more common in female patients (P = 0.019; OR, 3.3; 95% CI, 1.3 to 10) and cyclin DI expression was more frequent (chi-square(1), 3.96; P = 0.046) and at higher levels (P = 0.004) in tumors from female pat ients. In summary, our data show that the two CCND1 polymorphic sites are i ndependently associated with tumor biology and clinical outcome. CCND1 A/G( 870) alleles affect gene expression In head and neck tissues. We also provi de preliminary evidence that the molecular genetics of SCCHN development ma y be influenced by patient gender.