N-acetyltransferase gene polymorphisms in head and neck cancer.

B113

Objective: Head and neck cancer (HN) is the sixth most frequently observed cancer type in the world. Previous studies suggest that genetic susceptibility plays a significant role in the cancer risk and inherited polymorhisms of N-acetyltransferase genes functioning in the carcinogen metabolism may modulate the underlying genetic susceptibility. There are very few studies investigating the NAT gene polymorphisms in HN. In this study, the polymorphic changes in the NAT1 and NAT2 genes were investigated and associations between the allele and genotype frequencies and clinicopathological features of the patients were evaluated. Methods: Peripheral venous blood of 95 patients with HN and of 93 healthy people were analyzed. DNA was isolated from blood samples by phenol-chlorophorm extraction. Polymorphic regions of the NAT1 [NAT1*4, NAT1*3 (C1095A), NAT1*10 (T1088A, C1095A), NAT1*11 (9 bp deletion)] and NAT2 [NAT2*4, NAT2*5 (C481T), NAT2*6 (G590A), NAT2*7 (G857A)] genes were amplified by PCR. The products were digested with restriction enzymes and visualized in a video gel documentation system or the Agilent 2100 bioanalyzer. Polymorphic distributions were compared with the allele frequencies in the control group by using the De-Finetti case-control statistic programme and correlations with clinical parameters were evaluated by χ² (Chi-square) test. Results: No association was observed between the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and NAT2*6 genotypes and risk of HN. The NAT2*7 polymorphism correlated significantly with reduced risk of disease [p=0.0385, χ²=4.28, OR(%95CI)= 0.500 (0.258-0.970)]. A significant association was also observed between the NAT1*4/3 genotype and younger age (≤45) at onset (p=0.0427) and between the combined NAT2*4/5 genotype and histopathology (p=0.0434) and between the combined NAT2*4/6 genotype and tobacco consumption (p=0.0277). Conclusion: Our findings indicate that the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and NAT2*6 alleles are not implicated in HN but the NAT2*7 allele may play a protective role in head and neck carcinogenesis.