O6-methylguanine-DNA methyltransferase gene coding region polymorphisms and oral cancer risk.
BACKGROUND
O (6) -methylguanine-DNA methyltransferase (MGMT) is a specific DNA direct reversal repair protein which ameliorates mutagenic, carcinogenic and cytotoxic adducts from O(6) -methylguanine in DNA. The aim of this study was to investigate the potential association between six polymorphisms in the coding region of the MGMT gene and oral cancer risk in Taiwanese population.


METHODS
In this hospital-based case-control study, the MGMT genotypes were determined by using DNA sequencing in 176 patients with oral squamous cell carcinoma (OSCC), 77 patients with oral premalignant lesions and 110 normal individuals.


RESULTS
Although L53L and L84F polymorphisms were in complete linkage disequilibrium, no statistically significant association was found between the MGMT genotypes and haplotypes and oral cancer risk. We could also not detect any variations in the codon 65, 143, 160 and 178 within the coding region of the MGMT gene in both patients and controls. After stratification of OSCC patients by their mean age (54 years old), however, a higher overall survival rate with CT genotype than CC genotypes of the L53L polymorphisms was found in older patients (P=0.031). A borderline significance (P=0.074) between these genotypes and recurrence-free survivals has also been noted. The same results were also observed in L84F polymorphism.


CONCLUSIONS
The present study did not find statistically significant association between six common MGMT polymorphisms and oral cancer risk, however, both MGMT L53L and L84F polymorphisms in old patients with CT genotype have higher overall survival rates than patients with CC genotype. Because of limited power of the present study, further study may be warranted in ethnically different populations to explore outcomes of these polymorphisms in the oral cancer risk.
Huang
Sung-Hsien
SH
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Chang
Pei-Yang
PY
Liu
Chung-Ji
CJ
Lin
Ming-Wei
MW
Hsia
Kan-Tai
KT
D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D003596:Cytosine; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D013624:Taiwan; D013941:Thymine
D003062:Codon; D010649:Phenylalanine; D003596:Cytosine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D007930:Leucine; D013941:Thymine