Open AccessAssociations among smoking, MGMT hypermethylation, TP53-mutations, and relapse in head and neck squamous cell carcinoma
Author(s) -
Shinichi Matsuda,
Aki Mafune,
Nagisa Kohda,
Takanori Hama,
Mitsuyoshi Urashima
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0231932
Subject(s) - head and neck squamous cell carcinoma , dna methylation , oncology , medicine , methyltransferase , odds ratio , carcinogenesis , o 6 methylguanine dna methyltransferase , hazard ratio , epigenetics , cancer research , head and neck cancer , cancer , methylation , biology , confidence interval , gene , genetics , gene expression
Background Epigenetic silencing of the O 6 -methylguanine-DNA methyltransferase ( MGMT ) DNA repair enzyme via promoter hypermethylation (hm MGMT ) may increase mutations in the TP53 oncosuppressor gene and contribute to carcinogenesis. The effects of smoking, which is a risk factor for head and neck squamous cell carcinoma (HNSCC), were investigated to determine whether they up- or down-regulate hm MGMT . Additionally, the impact of hm MGMT and disruptive TP53 -mutations on relapse was investigated in patients with HNSCC. Methods This study included 164 patients with HNSCC who were negative for both p16 protein expression and human papilloma virus infection. The association of smoking and hm MGMT was investigated using multiple logistic regression analysis. Competing risk regression was used to evaluate the effects of hm MGMT and TP53 -mutations in exon 2 to 11 on relapse of HNSCC. Results hm MGMT was observed in 84% of the 164 patients. TP53 -mutations, specifically, G:C>A:T transition, were more frequent in patients with hm MGMT (32%) than in those without hm MGMT (8%). The frequency of disruptive TP53 -mutations was not significantly different between groups. Compared with nonsmoking, heavy smoking of 20 pack-years or more was significantly associated with decreased hm MGMT (adjusted odds ratio, 0.08; 95% CI, 0.01 to 0.56; P = 0.01). Patients who had both hm MGMT and disruptive TP53- mutations showed a significantly higher relapse rate than all other patients (subdistribution hazard ratio, 1.77; 95% CI, 1.07 to 2.92; P = 0.026). Conclusions It was found that hm MGMT was suppressed by heavy smoking, and hm MGMT combined with disruptive TP53- mutations may indicate a poor prognosis in patients with HNSCC.