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CYP1A1 is the phase I enzyme that detoxifies the carcinogen or converts it into a more electrophilic form, metabolized by phase II enzymes like GSTP1. These detoxifying genes have been extensively studied in association with head and neck cancer (HNC) in different ethnic groups worldwide. The current study was aimed at screening genetic polymorphisms of genes CYP1A1 and GSTP1 in 388 Pakistani HNC patients and 150 cancer-free healthy controls, using PCR-SSCP. No already known variants of either gene were found, however a novel frameshift mutation due to insertion of T (g.2842_2843insT) was observed in the CYP1A1 gene. A statistically significant number (5.4%) of HNC cases, with the mean age of 51.75 (±15.7) years, presented this frameshift mutation in the conserved domain of CYP1A1. Another novel substitution mutation in was found in the GSTP1 gene, presenting TA instead of AG. The g.2848A &gt; T polymorphism causes a leucine-to-leucine formation, whereas g.2849G &gt; A causes alanine-to-threonine formation at amino acid positions 166 and 167, respectively. These exonic mutations were found in 9.5% of the HNC patients and in none of the controls. In addition, two intronic deletions of C (g.1074delC and g.1466delC) were also found in 11 patients with a mean age of 46.2 (±15.6) years. In conclusion, accumulation of mutations in genes CYP1A1 and GSTP1 appears to be associated with increased risk of developing HNC, suggesting that mutations in these genes may play a role in the etiology of head and neck cancer.

Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients