Hypermethylation of carcinogen metabolism genes, CYP1A1, CYP2A13 and GSTM1 genes in head and neck cancer.
OBJECTIVE
To investigate the role of aberrant hypermethylation of carcinogen metabolism pathway genes, CYP1A1, CYP2A13 and GSTM1 in head and neck cancer independently as well as its relation to tobacco and alcohol consumption and CYP1A1 and CYP2A13 polymorphisms in Indian population.


METHODS
Seventy-three histologically confirmed head and neck cancer patients undergoing treatment in Postgraduate Institute of Medical Education and Research, Chandigarh, India were recruited. Non-cancerous tissues were obtained from 19 trauma subjects undergoing maxillofacial surgery. Methylation-specific PCR was performed to determine the methylation status of selected genes.


RESULTS
The aberrant hypermethylation of CYP1A1, CYP2A13 and GSTM1 genes was found in cancer tissues with frequency of about 39.7%, 27.4%, and 58.1%, respectively, and in normal healthy tissues with a frequency of about 10.5%, 15.8%, and 20.0%, respectively. Hypermethylation of CYP1A1 (P 0.027) and GSTM1 (P 0.010) showed significant association with head and neck cancer. We also observed significant interaction between smoking and methylation status of CYP1A1 (P 0.029) and CYP2A13 (P -0.034) in head and neck cancer. No association was observed between methylation status and alcohol consumption, clinical features and genetic polymorphisms of CYP1A1 and CYP2A13.


CONCLUSIONS
Hypermethylation of carcinogen metabolism pathway genes independently and in interaction with smoking is associated with increased risk of head and neck cancer.
Sharma
R
R
Department of Otolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Panda
N K
NK
Khullar
M
M
D000225:Adenine; D000428:Alcohol Drinking / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002273:Carcinogens / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D003596:Cytosine; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006147:Guanine; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007194:India; D007822:Laryngeal Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012907:Smoking / Q000235:genetics; D013941:Thymine
D000225:Adenine; D001189:Aryl Hydrocarbon Hydroxylases; D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D003596:Cytosine; D005982:Glutathione Transferase; D006147:Guanine; D013941:Thymine; C414206:CYP2A13 protein, human