Complex Interplay of CYP1A1 Genetic Polymorphism on Colorectal Cancer Susceptibility

Document Type : Original Article

Authors

1 Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University

2 Department of General Surgery, Faculty of Medicine, Cairo University

Abstract

Colorectal cancer (CRC) is one of the most common malignancies in developed
countries. It occurs via an interaction between an individual genetic background and
environmental parameters such as dietary factors. A number of studies have
suggested that dietary procarcinogens, such as heterocyclic amines, N-nitroso
compounds and polycyclic aromatic hydrocarbons, might be related to the
carcinogenesis of CRC. The carcinogens that cause the development of CRC enter the
body as procarcinogens via transporters and are activated to carcinogens or
eliminated by various enzymes. These toxicokinetic-related proteins are also
controlled by our genetic background (e.g. by genetic polymorphisms).Aim of work:
To analyze the common genetic polymorphisms in the genes for the metabolic
enzymes CYP1A1 in an attempt to elucidate the association between these
polymorphisms and sporadic cases of colorectal carcinoma among Egyptian patients.
Subjects and Methods: This is a prospective controlled study where we investigated
the association between polymorphism of cytochrome P4501A1 (m2) and colorectal
cancer using PCR-RFLPS. Over a period of twenty one months, the present study
included forty patients with colorectal carcinoma diagnosed by histopathological
examination of tumor biopsy and not on chemotherapy or radiotherapy. Twenty
healthy subjects, matched for age and sex were included as a control group. For all
subjects, peripheral blood samples were assayed for genetic polymorphism of
CYP1A1.Results: Our results showed that a statistically significant association
existed between CYP1A1 variant genotype (p=0.015 and the odds ratio OR=0.105
with the 95% confidence interval 0.028-0.390) and colorectal cancer. Conclusion:
The studied polymorphism may be associated with the risk of development of
colorectal carcinoma in Egyptian patients however, large scale studies are essential
to confirm that association.

Keywords