Patient and control subjects were found to have similar allelic frequencies of the CCND1 polymorphism (A allele 0.54 for patients and 0.51 for controls; p = 0.47) and genotypes distribution (AA 32%, AG 44%, GG 24% for patients and AA 25%, AG 51%, GG 24% for controls; p = 0.47) (Table 1). Allelic frequencies (A allele 0.54) and genotype distribution (AA 36%, AG 36%, GG 28%) of patients who were less than 60 years of age also did not differ from those of the controls (p = 0.65 and p = 0.19, respectively).

      Age and gender of patients, as well as localization or the Dukes' stage of tumors, did not influence the allelic frequencies and genotype distribution of the CCND1 polymorphism (p >0.1 in all instances). Although the number of patients was small, a statistically significant difference in CCND1 polymorphism frequencies was found when patients less than 60 years of age were analyzed in relation to the MSI status of their tumors (Table 2). Comparison of the distribution of AA and AG genotypes in this group of patients suggested that the A allele acts as a dominant trait [Odds Ratio 4.69, 95% Confidance Interval 1.02-21.54, p = 0.046].

      Our data indicate that the CCND1 polymorphism may influence the age at onset of colorectal cancer in young patients only when their tumors exhibit an MSI phenotype. This conclusion is in agreement with the initial findings of Kong et al. [14] for the influence of this variant in HNPCC kindreds, since MSI phenotype is present in almost all tumors of patients with this condition [17]. The most likely explanation for these findings is that units of the cyclin D1 regulated cell cycle control system are frequently inactivated by the MSI phenotype, thus potentiating the proliferative activity of the aberrant CCND1 protein produced from the A allele. However, such an association was not found by McKay et al. [11] and by Bala et al. [15], which further potentiates the complexity of the genetic predisposition for the development of colorectal cancer.

Table 1. Allelic frequencies and genotype distribution of the G870A polymorphism in the CCND1 gene in colorectal cancer patients and control subjects.