Gene-environment interactions in determining differences in genetic susceptibility to cancer in subsites of the head and neck.
Genetic differences in susceptibility to cancer in subsites of the head and neck were investigated in a case-control study involving 750 cases of cancers of the oral cavity, larynx, or pharynx, and an equal number of healthy controls. The prevalence of variant genotypes of cytochrome P450 (CYP) 1A1, 1B1, 2E1, or glutathione-S-transferase M1 (null) in cases suggests that polymorphisms in drug metabolizing enzymes (DMEs) modify cancer risk within subsites of the head and neck. Tobacco or alcohol use was found to increase the risk in cases of laryngeal, pharyngeal, or oral cavity cancers. Interaction between genetic variation in DMEs and tobacco smoke (or smoking) exposures conferred significant risk for laryngeal cancer. Likewise, strong associations of the polymorphic genotypes of DMEs with cases of pharyngeal and oral cavity cancer who were tobacco chewers or alcohol users demonstrate that gene-environment interactions may explain differences in genetic susceptibility for cancers of the oral cavity, larynx, and pharynx.
Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow, Uttar Pradesh, India; Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
Shailendra S
SS
Maurya
Tridiv
T
Katiyar
Ankur
A
Dhawan
Sudhir
S
Singh
Swatantra K
SK
Jain
Mohan C
MC
Pant
Devendra
D
Parmar
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase
CYPs; GSTM1; head and neck squamous cell carcinoma; interaction; risk