Genotyping of CYP3A5 Polymorphisms among Bulgarian Patients with Sporadic Colorectal Cancer and Controls

Abstract

The purpose of the study was to genotype four polymorphisms in CYP3A5 (CYP3A5*2, CYP3A5*3, CYP3A5*3B, and CYP3A5*6) for a possible association between individual genetic variations and susceptibility to colorectal cancer. Another point of interest was to conduct a comprehensive analysis in tumor and normal intestine tissue from the same patient, searching for somatic hotspots. Material and Methods: In our study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy volunteers were enrolled. CYP3A5 polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analysis on a LightCycler™. Results: The allele frequencies were comparable in both groups: frequency of CYP3A5*2 = 0.3% in patients vs. 0.6% in controls; frequency of CYP3A5*3 = 90.8% in patients vs. 93.1% in controls; in both groups no CYP3A5*3B and CYP3A5*6 variants were detected (p > 0.05). No difference was observed between genotype frequencies in tumor and surrounding normal tissues of 80 patients. Conclusions: The CYP3A5 variants are unlikely to have an important functional significance in patients with colorectal cancer. The studied CYP3A5 loci do not seem to be hotspots for somatic mutation. DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA for genotyping of these polymorphisms.

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

“…Similar frequencies of the CYP3A5*3 allele (91% in 146 patients and 93% in 160 controls) were detected among Bulgarians in a study on the predisposition to colorectal cancer [38]. Further, within these patients and controls there were almost identical frequencies of the minor MDR-1 alleles: 43.5% and 44.1% for the T2677 allele and 48.3% and 50.9% for the 3435T allele [39].…”

PharmGKB summary

“…CYP3A5*2 (rs28365083; g.27289C > A; T398N), considered to be not fully functional [11], was found at a frequency of 1% in a group of 500 Dutch Whites [11], 1.3% in a population of 124 Whites [13], and 0.3% in a group of 146 Bulgarian Whites [14]. This variant has not been found when assayed for in other populations [15–18].…”

L’impact des polymorphismes ABCB1 et CYP3A5 sur le cancer colorectal dans la population de l’Ouest Algérien: Etude cas-témoins

“…Sachant que l'allèle CYP3A5*3 est synonyme d'une expression plus faible voire nulle de l'enzyme CYP3A5, il semblerait que dans notre population, l'expression de CYP3A5 serait plus faible et donc que la perte de l'expression de cette enzyme due au polymorphisme CYP3A5 c.6986A>G n'ait pas de lien avec une susceptibilité accrue au CCR. Ceci est en accord avec les conclusions d'autres études [21,22].…”