Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes

• Published in: Head & neck Vol. 30; no. 9; pp. 1139 - 1147
• Main Authors: Buch, Shama C., Nazar-Stewart, Valle, Weissfeld, Joel L., Romkes, Marjorie
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2008; John Wiley & Sons
• Subjects: Adolescent; Adult; Aged; Arylamine N-Acetyltransferase - genetics; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - ethnology; Carcinoma, Squamous Cell - genetics; Case-Control Studies; Chi-Square Distribution; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P-450 CYP2E1 - metabolism; Female; Gene Expression Regulation, Enzymologic - genetics; Genetic Predisposition to Disease; Genotype; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Humans; Male; Medical sciences; metabolizing enzymes; Middle Aged; Mouth Neoplasms - enzymology; Mouth Neoplasms - ethnology; Mouth Neoplasms - genetics; Odds Ratio; oral cancer; Oropharyngeal Neoplasms - enzymology; Oropharyngeal Neoplasms - ethnology; Oropharyngeal Neoplasms - genetics; Otorhinolaryngology. Stomatology; polymorphism; Polymorphism, Single Nucleotide; Reference Values; Risk Assessment; Survival Analysis; susceptibility; tobacco; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; White People - genetics; susceptibility; Oral cancer; metabolizing enzymes; Enzyme; Stomatology; Oropharynx cancer; ENT; Malignant tumor; Case control study; Sensitivity; Tobacco; ENT disease; Genetics; Oral cavity disease; Pharynx disease; Cancer; Polymorphism
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.20867

Background. Genetic variation in xenobiotic metabolizing enzymes may explain differing susceptibilities to the cancer causing effects of tobacco and alcohol. Methods. We compared 203 oral squamous cell carcinoma cases and 416 controls for single nucleotide polymorphisms (SNPs) in 8 genes (CYP1A1, CYP2E1, MPO, mEH, GSTM1, GSTT1, GSTP1, and NAT2). Except for NAT2, genotype frequencies were similar in the 2 groups. We classified subjects as fast or slow NAT2 acetylators genotyping 13 NAT2 SNPs. Results. Fast acetylators were overrepresented in cases (53.7%) compared with controls (43.9%; odds ratio (OR) 1.55, 95% confidence interval (CI) 1.08–2.20; p value = .03). Gene–gene interaction testing suggested several cancer‐NAT2 associations, with association strongest among persons without a CYP1A1 variant (*2C or *4) allele (OR 1.77, 95% CI 1.20–2.60, p value = .03) or with a variant MPO (463A) allele (OR 2.38, 95% CI 1.34–4.21, p value = .05). Conclusion. These results implicate fast NAT2 acetylation as a risk factor for oral cancer. © 2008 Wiley Periodicals, Inc. Head Neck 2008