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
functional polymorphisms, such as CYP3A5*3
could alter individual susceptibility to lung cancer.
The results of their study suggested that the
carriers of this allele are at lower risk of developing
advanced lung caner probably due to decreased
activation of procarcinogens present in the tobacco
smoke.
The CYP3A5*1 allele represent wild type
which has faster kinetics of metabolising various
drugs and environment carcinogens. In general,
when chemical compounds enter the body, the
phase I enzymes will metabolize these compounds
into procarcinogens and they are more active than
parent compounds. This indicates the possibility
that wild type allele with faster kinetics can form
more active procarcinogens leading to
development of breast cancer. The CYP3A5*3
allele cannot metabolize compounds and results
in accumulation of environmental compounds
which might also act as carcinogens (2).
The frequency of 3/3 genotype was
increased in postmenopausal women (40.0%)
with breast cancer. Postmenopausal women tend
to have prolonged exposure to carcinogens during
lifetime, which might predispose them to develop
breast cancer especially with CYP3A5*3 allele
as it is inefficient to metabolize the carcinogenic
compounds. There was a slight increase of 1/3
genotype in patients with positive family history,
which suggest that these genes might play
important role in causing germline mutations in
major candidate genes leading to familial
susceptibility to develop cancer.
Higher frequency of 3/3 genotype was
found to be present in patients with obesity. The
environmental carcinogens, which enter into body,
are generally stored in adipose tissue and may
form DNA adducts in individuals who has lower
activity of CYP3A5 gene. So the patients with 3/
3 genotype as well as elevated BMI carry
increased risk to develop breast cancer. When
184
occupation of breast cancer was considered, the
frequency of homozygous (3/3) genotype was
increased in patients who are housewives (60.7%)
and heterozygous (1/3) genotype was increased
in agricultural laborers (55.6%) which suggested
that the CYP3A5 dependent risk of developing
breast cancer depends on the type of exposure
to different environmental compounds as well as
drugs used for various medical reasons (Table
1).
The frequency of 3/3 genotype was increased
in patients with estrogen and progesterone
receptor positive status indicating that individuals
with positive hormonal receptor status and
3/3 genotype carry higher risk to develop cancer.
Higher frequency of patients with 3/3 genotype
were found to be positive HER2/neu status. No
significant association was observed when
CYP3A5*1 gene with respect to stage of the
breast cancer and nodal status of the patients,
which indicated that CYP3A5*3 polymorphism
might not be a contributing factor in the progression
of the disease (Table 2).
In the present study, the CYP3A5*6 allele
was not observed in breast cancer cases as
well as in controls. Our results are in accordance
with other studies on Taiwan and Korean population
who did not report the CYP3A5*6 allele
(6,7).
In conclusion our results suggested that
the CYP3A5*3 polymorphism might influence the
breast cancer etiology which mainly depends on
the type of exposure.
Acknowledgments
This work was supported by University
Grants Commission, New Delhi, India and
Nizam’s Institute of Medical Sciences,
Hyderabad, India.
Surekha et al