Effect of age on the association between p16CDKN2A methylation and DNMT3B polymorphism in head and neck carcinoma and patient survival.
De novo DNA methylation is a relevant epigenetic mechanism, which represses gene transcription and commonly inactivates tumor suppressor genes in carcinogenesis. A single nucleotide polymorphism of DNMT3B, C46359T (-149C-->T) was reported to modulate individual's susceptibility to cancer. We investigated the role of this polymorphic variant regarding the methylation status of the p16CDKN2A gene in young and older patients with head and neck squamous cell carcinoma (HNCC) matched by the TNM staging system, together with its impact on patients survival. The results showed that the presence of the allele T of the polymorphism DNMT3B (-149C-->T) was associated with advanced TNM staging and smoking habit, but no association was found between this polymorphisms and DNMT3B immunostaining. While p16CDKN2A methylation was significantly associated with smoking habit in older patients, this parameter was associated with family history of cancer in young patients. Moreover, in older patients the absence of p16CDKN2A promoter methylation had a negative impact on survival. In conclusion, nucleotide polymorphism of DNMT3B is not associated with methylation of p16CDKN2A gene in HNSCC. The association of p16CDKN2A gene methylation with smoking, family history of cancer and survival is dependent on age.
Farias
Lucyana Conceição
LC
Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Belo Horizonte, Brazil.
Fraga
Carlos Alberto De Carvalho
CA
De Oliveira
Marcos Vinícius Macedo
MV
Silva
Thiago Fonseca
TF
Marques-Silva
Luciano
L
Moreira
Paula Rocha
PR
De-Paula
Alfredo Maurício Batista
AM
Gomez
Ricardo Santiago
RS
Guimarães
André Luiz Sena
AL
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000401:mortality*; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000502:physiology; D005192:Family Health; D005260:Female; D019942:Genes, p16; D055106:Genome-Wide Association Study; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B