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.
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.
Authors: Y Ko; J Abel; V Harth; P Bröde; C Antony; S Donat; H P Fischer; M E Ortiz-Pallardo; R Thier; A Sachinidis; H Vetter; H M Bolt; C Herberhold; T Brüning Journal: Cancer Res Date: 2001-06-01 Impact factor: 12.701
Authors: Anne M Hakenewerth; Robert C Millikan; Ivan Rusyn; Amy H Herring; Kari E North; Jill S Barnholtz-Sloan; William F Funkhouser; Mark C Weissler; Andrew F Olshan Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-09-22 Impact factor: 4.254
Authors: Jesse D Troy; Joel L Weissfeld; Brenda Diergaarde; Ada O Youk; Shama C Buch; Marjorie Romkes; Jennifer R Grandis Journal: Cancer Epidemiol Date: 2013-03-21 Impact factor: 2.984