Abstract
In the current case control study, 94 pharyngeal, 67 laryngeal cancer cases and 150 cancer free controls were screened via PCR-SSCP assay. Mean ages of pharyngeal, laryngeal cancer patients and control was 48.14 (± 16.7), 48.56 (± 17.4) and 46 (± 17.69) years respectively. Results revealed two novel mutations in CYP1A1 gene, a substitution mutation of A2842C resulting in missense tyrosine to serine formation and frameshift mutation due to insertion of thymidine at nucleotide 2842 resulting in 495 nucleotide sequences to alter. It was found that 3.2% pharyngeal and 2.98% laryngeal cancer patients had these mutations in CYP1A1. In GSTP1 gene exon 7, an A2848T substitution causes a leucine to leucine formation whereas G2849A substitution causes alanine to threonine formation at amino acid 166 and 167 respectively. These exonic mutations were found in 7.4% pharyngeal cancer and 9% laryngeal cancer patients. Two intronic deletions of C at nucleotide 1074 and 1466 were found in 1% pharyngeal and laryngeal cancer patients. Accumulation of mutations in CYP1A1 and GSTP1 genes seem to be associated with increased risk of pharyngeal and laryngeal cancer development.
Highlights
Polymorphisms in the carcinogen detoxifying gene may increase or decrease carcinogen activation or detoxification followed by variation of cancer risk [1]
Most of the carcinogenic moieties are metabolically processed by xenobiotic-metabolizing enzymes in two broad steps: phase I mediated by Cytochrome p450s (CYPs) and phase II catalyzed by glutathione S-transferases (GSTs)
No already reported polymorphisms in CYP1A1 gene were found in the current study
Summary
Polymorphisms in the carcinogen detoxifying gene may increase or decrease carcinogen activation or detoxification followed by variation of cancer risk [1]. Phase I reactions expose functional groups of the substrates and yield highly reactive intermediates. These intermediates form the substrates for phase II reactions that involve their conjugation with endogenous molecules such as glutathione (GSH) and facilitate their elimination. The coordinated expression and regulation of phase I and II enzymes determines the outcome of carcinogen exposure. Sequence variants or polymorphisms in these genes can alter the expression, function and/or activity of these enzymes and, in turn, cancer risks [2]
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