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Background  Smoking induces oncogenic  TP53-mutations  in head and neck squamous cell carcinomas (HNSCCs). Disruptive mutations of  TP53 -gene and expression of  p16  protein [ p16 (+) ] in tumor tissue associate with worse and better prognosis, respectively. UDP-glucuronosyltransferase 2 family, polypeptide B17 ( UGT2B17 ) detoxifies smoking-related metabolites. Differences among ethnic groups in  UGT2B17  are extremely high. Homozygous deletions of  UGT2B17  gene ( UGT2B17 -deletion) are a common copy number variant (CNV) among Japanese, but not a common CNV among Africans and Europeans. Thus, we examined Japanese patients with HNSCC to explore if  UGT2B17- deletion and/or  p16 (+)  modify effects of smoking on  TP53-mutations  and affect relapse.    Methods  We conducted a posthoc analysis of a prospective cohort. Polymerase chain reaction, immunohistochemistry, and direct sequencing were used to determine  UGT2B17 -deletion,  p16  (+), and detailed  TP53 -mutations, respectively.    Results   UGT2B17 -deletion was observed in 80% of this study population. For this 80%,  TP53-mutations  were significantly more common among smokers than non-smokers ( P  = 0.0016), but this difference between smokers and nonsmokers was not significant for the 20% with  UGT2B17 . In patients with  UGT2B17 -deletion and  p16 (+),  simultaneously,  TP53-mutations  were much more common among smokers than among non-smokers (81% versus 17%;  P  = 0.0050). Patients with both  UGT2B17 -deletion and disruptive  TP53-mutations  had higher relapse rates than other patients (hazard ratio, 2.22; 95% confidence interval, 1.30 to 3.80,  P  = 0.004) in a stepwise method.    Conclusions  These results suggest that  UGT2B17 -deletion interacting with  p16  (+) may modify effects of smoking on  TP53-mutations  and may further interact with the disruptive  TP53-mutations  to raise relapse rates among Japanese patients with HNSCC.

Homozygous deletions of UGT2B17 modifies effects of smoking on TP53-mutations and relapse of head and neck carcinoma