High frequency of microsatellite instability in young patients with head-and-neck squamous-cell carcinoma: lack of involvement of the mismatch repair genes hMLH1 AND hMSH2.
The most prevalent risk factors in the development of head-and-neck squamous-cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption. In young patients with HNSCC, these risk factors are often absent. Our purpose was to investigate the risk factors, microsatellite instability (MSI) changes and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of young patients with HNSCC. Fifty-seven HNSCC tumors were examined for the presence of MSI at 16 microsatellite sites using PCR. In the young patient group (24 cases, < or = 44 years old), 100% of tumors had MSI at 1 site at least and 88% had MSI at 2 or more loci. In older patients (33 cases, > or = 45 years), MSI at 1 or more sites was found in 61% of tumors (young vs. old, p = 0.0003) and instability at 2 or more sites was found in 36% of tumors (young vs. old, p = 0.0001). The involvement of the mismatch repair genes was investigated by examining promoter methylation, exon mutation and gene expression of hMLH1 and hMSH2. All results were negative, indicating that inactivation of these 2 genes does not play a role in the development of MSI in tumors from this patient group. Furthermore, the young patient group had a significantly lower incidence of smoking (46% young, 88% old; p = 0.001) and alcohol consumption (33% young, 67% old; p = 0.0169), emphasizing the probable importance of other environmental and/or genetic factors in the development of their disease.
Wang
Y
Y
Department of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
Irish
J
J
MacMillan
C
C
Brown
D
D
Xuan
Y
Y
Boyington
C
C
Gullane
P
P
Kamel-Reid
S
S
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008745:Methylation; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012867:Skin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein