Cyclin D1 polymorphism and the susceptibility to NPC using DHPLC.

ABSTRACT

Cyclin D1 is a key cell cycle regulator and a candidate proto-oncogene, whose deregulation has been implicated in pathogenesis of several types of cancers, including NPC. A common A/G polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to some phenotypes of several tumors. To investigate the influence of cyclin D1 genotypes on the genetic susceptibility in humans from Southern China to sporadic nasopharyngeal carcinoma, cyclin D1 genotyping was performed by denaturing high performance liquid chromatography (DHPLC) and DNA sequencing analysis of the PCR products from 84 NPC cases and 91 normal controls. Gene frequency distribution was tested by Hardy-Weinberg equilibrium and comparison of cyclin D1 gene frequencies between the patient and control groups was performed by chi 2 test. Results showed that in NPC patients, the AA genotype of CCND1 was significantly lower (20.24%) than in normal controls (38.46%), and the GG and AG genotypes (GG + AG) were significantly higher in NPC group than in the control group (chi 2 = 6.946, P corrected = 0.016, OR = 2.463, 95% CI = 1.249-4.859). These suggest that the A/G polymorphism of CCND1 was associated with the susceptibility to NPC, and the GG and AG genotypes in NPC patients were significantly higher than those in normal controls.