April Journal-2009.p65 - Association of Biotechnology and Pharmacy

Current Trends in Biotechnology and Pharmacy
Vol. 3 (2) 181-187, April 2009. ISSN 0973-8916
Association of CYP3A5*3 and CYP3A5*6 Polymorphisms with
Breast Cancer Risk
Surekha D, Sailaja K, Nageswara Rao D, Padma T,
Raghunadharao D 1 and Vishnupriya S*
Department of Genetics, Osmania University, Hyderabad, India
1
Department of Medical Oncology, Nizams Institute of Medical Sciences
Hyderabad, India
*For Correspondence - sattivishnupriya@gmail.com
Abstract
CYP3A5 gene is located on chromosome
7q21.1 and is responsible for the metabolism of
over 50% of all clinically used drugs. 250 breast
cancer and same number of healthy age matched
controls were analyzed for the polymorphisms of
CYP3A5*3 and CYP3A5*6 by polymerase
chain reaction-restriction fragment length
polymorphism. The normal wild type allele
CYP3A5*1 produces correct transcript and
individuals with at least one CYP3A5*1 allele can
express CYP3A5 at higher levels. In the present
study, the frequency of heterozygotes for
CYP3A5*1 (1/3) was significantly increased in
breast cancer (53.0%) when compared to controls
(41.4%) with corresponding increase in
CYP3A5*1 allele frequency. The frequency of
3/3 genotype was increased in postmenopausal
(40.0%) patients with high BMI, ER, PR and
HER2/neu positive status and in housewife group.
There was an increase of 1/3 genotype frequency
in patients with positive family history and
agricultural laborers (55.6%). In conclusion our
results suggested that the CYP3A5*3
polymorphism might influence the breast cancer
etiology which mainly depends on the type of
exposure. CYP3A5*6 allele was not observed in
cases as well as in controls.
Keywords: Polymorphisms; Breast cancer;
Receptor status
Introduction
CYP3A enzymes are the most abundantly
expressed cytochrome P450 enzymes in liver and
are responsible for the metabolism of over 50%
of all clinically used drugs (1) Gellner et al (2)
had identified a 231-kb region on chromosome
7q21.1 containing 3 CYP3A genes: CYP3A4,
CYP3A5 and CYP3A7, as well as 3 pseudogenes
and a novel CYP3A gene, which they termed
CYP3A43. Jounaidi et al (3), isolated the 5-prime
flanking region of CYP3A5 from a genomic clone
on chromosome 7. Promoter analysis determined
that CYP3A5 uses a CATAA box, rather than a
TATA box at positions -23 to -28 and has a basic
transcription element from -35 to -50.
Kuehl et al (4) stated that variation in the
CYP3A enzymes could influence circulating
steroid levels and responses to 50% of oxidatively
metabolised drugs. CYP3A activity was the sum
activity of the family of CYP3A genes, including
CYP3A5, which was polymorphically expressed
at high levels in a minority of Caucasians. Only
individuals with at least one CYP3A5*1 (wild
type) allele express large amounts of CYP3A5.
Kuehl et al (4) demonstrated that SNPs in
CYP3A5*3 (6986A-G) and CYP3A5*6 (a G-
to-A transition in exon 7 resulting in deletion of
that exon) cause alternative splicing and protein
truncation, resulting in the absence of CYP3A5
from tissues of some people. Because CYP3A5
CYP3A5*3 and CYP3A5*6 Polymorphisms and Breast Cancer