Research article

Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients

Guillermo Gervasini¹ , Elena García-Martín² , José M Ladero³ , Rosa Pizarro¹ , Javier Sastre⁴ , Carmen Martínez¹ , Monserrat García¹ , Manuel Diaz-Rubio³ and José AG Agúndez¹

¹  Department of Pharmacology & Psychiatry, University of Extremadura, Badajoz, Spain

²  Department of Biochemistry & Molecular Biology & Genetics, University of Extremadura, Badajoz, Spain

³  Service of Gastroenterology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain

⁴  Service of Oncology Hospital Clínico San Carlos, Complutense University, Madrid, Spain

author email corresponding author email

BMC Cancer 2007, 7:118doi:10.1186/1471-2407-7-118

Published:	2 July 2007

Abstract

Background

Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.

Methods

CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals.

Results

The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: CYP3A4*1B, 4.8 % (95% C.I. 2.6–7.0), 3.7 % (0.8–6.6) 4.3% (2.0–6.6) and 4.3% (2.1–6.5); CYP3A5*3, 91.8 % (93.0–97.4), 95.7% (92.6–98.8), 91.7% (88.6–94.8) and 90.8% (87.7–93.9). The association between CYP3A4*1B and CYP3A5*3 variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage.

Conclusion

Common polymorphisms on CYP3A4 and CYP3A5 genes do not modify the risk of developing digestive cancers in Western Europe.