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


CONCLUSIONS
These results implicate fast NAT2 acetylation as a risk factor for oral cancer.
Buch
Shama C
SC
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Nazar-Stewart
Valle
V
Weissfeld
Joel L
JL
Romkes
Marjorie
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D009959:Oropharyngeal Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D044465:White People / Q000235:genetics*
D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase