Hypermethylation, risk factors, clinical characteristics, and survival in 235 patients with laryngeal and hypopharyngeal cancers.
BACKGROUND
It has been established that promoter hypermethylation occurs in several genes during the pathogenesis of head and neck cancer. The authors investigated the role played by the hypermethylation of 4 cancer-related genes in the survival of patients who had laryngeal and hypopharyngeal cancer and in the occurrence of second primary tumors.


METHODS
Archival paraffin-embedded tissue (PET) samples were available from patients who were enrolled in a multicentric European case-control study that was performed between 1979 and 1982 and was followed up to 2000. Genomic DNA extracted from 235 PET samples were analyzed for promoter methylation status of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase (DAP-K), and E-cadherin genes by using a methylation-specific polymerase chain reaction assay.


RESULTS
Hypermethylation was present in 44% of samples for p16, in 27% of samples for MGMT, in 42% of samples for DAP-K, and in 43% of samples for E-cadherin. Hypermethylation of either individual genes or their combination was not associated with mortality from all causes, mortality from upper aerodigestive tract cancer, or the occurrence of second primary tumors.


CONCLUSIONS
The analysis of a large series of patients with laryngeal and hypopharyngeal cancer suggested that hypermethylation is a frequent event in laryngeal and hypopharyngeal cancer, but it is not a predictor of mortality or second primary cancer.
Dikshit
Rajesh P
RP
Department of Lifestyle, Environment, and Cancer, International Agency for Research on Cancer, Lyon, France.
Gillio-Tos
Anna
A
Brennan
Paul
P
De Marco
Laura
L
Fiano
Valentina
V
Martinez-Peñuela
Jose Maria
JM
Boffetta
Paolo
P
Merletti
Franco
F
D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality*; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate