Prospectus

Cytochrome P4501A Increases Activity and Risk of Prostate Cancer

Research Prospectus by:
Monée Casimir
Research Advisor:
Dr. Nathan Bowen
Department of Biological Sciences
Clark Atlanta University
Atlanta, Georgia
Literature Review
CYP1A2 expression and function was increased in smokers and decreased in patients with inflammation and cholestasis. Of 169 SNPs in 17 candidate genes including the CYP1A locus, 136 non-redundant SNPs with minor allele frequency >5% were analyzed by univariate and multivariate methods. A total of 13 strong significant associations were identified, of which 10 SNPs in the ARNT, AhRR, HNF1α, IL1β, SRC-1, and VDR genes showed consistent changes for at least two phenotypes by univariate analysis. Multivariate linear modeling indicated that the polymorphisms and non-genetic factors together explained 42, 38, and 33% of CYP1A2 variation at activity, protein and mRNA levels, respectively. In conclusion, we identified novel trans-associations between regulatory genes and hepatic CYP1A2 function and expression, but additional genetic factors must be assumed to explain the full extent of CYP1A2 heritability.

Nicotine exposure elevates cytochrome P450 1A2 levels correlating to prostate cancer progression (Pavanello, et. al 2012). CYP1A2 activity is not affected by nicotine and previous studies suggest high dosage of nicotine treatment has a low potential for communication with parallel CYP1A2 substrates (Hukkanen, et. al 2011). Nicotine has no role in the induction of CYP1A2 that is known to take place in smokers. Smoking is associated with a higher risk of cancer in various tissues, including the stomach, kidney, bladder, and pancreas, that are not in direct contact with tobacco smoke.
CYP1A2
Cytochrome P4501A2 (CYP1A2) is a part of the cytochrome P450 enzyme family that is a key enzyme for lung carcinogen activation and lung inflammation. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug

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