An association between the MICA-A5.1 allele and an increased susceptibility to oral squamous cell carcinoma in Japanese patients.
BACKGROUND
Recently, a new polymorphic gene family called the major histocompatibility complex class I chain-related gene A (MICA) was discovered about 40 kb centromeric to HLA-B gene. The MICA protein, expressed on epithelial cells and many kinds of tumor cells, serves to regulate immune function. The MICA protein is thought to activate immune function on mucosal tissue by binding to NKG2D which is expressed on most natural killer cells, CD8 positive T cells, and gamma delta T cells. An association between MICA gene polymorphisms and the development of oral squamous cell carcinoma (OSCC) has also been reported.


OBJECTIVE
This study was designed to test this association in Japanese patients with OSCC.


METHODS
The (GCT)(n) polymorphisms of the MICA gene was investigated in 123 patients with OSCC and 188 normal controls using polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis.


RESULTS
Five alleles, namely A4, A5, A6, A9, and A5.1, were found in both groups. The phenotype frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC when compared with normal controls (OR 1.707, 95% CI 0.76-3.45, P=0.042). Also, the microsatellite frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC compared with normal controls (OR 1.664, 95% CI 0.82-3.42, P=0.021). Lastly, the frequency of the MICA-A5.1 allele was significantly higher in those with lymph node metastasis from OSCC compared with normal controls (OR 2.605, 95% CI 1.14-5.27, P=0.026).


CONCLUSIONS
These results suggest that the MICA-A5.1 allele may be associated with an increased susceptibility to OSCC in Japan.
Tamaki
Shigehiro
S
Department of Oral and Maxillofacial Surgery, Nara Medical University, Nara, Japan. tamakitama@Zeus.eonet.ne.jp
Sanefuzi
Nobuyuki
N
Ohgi
Kazuhiko
K
Imai
Yuichiro
Y
Kawakami
Masayoshi
M
Yamamoto
Kazuhiko
K
Ishitani
Akiko
A
Hatake
Katsuhiko
K
Kirita
Tadaaki
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011110:Polymorphism, Genetic / Q000235:genetics*; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D018911:Trinucleotide Repeats / Q000235:genetics
D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell