The XRCC1 399Gln polymorphism and the frequency of p53 mutations in Taiwanese oral squamous cell carcinomas.
DNA repair gene polymorphisms have been implicated as susceptibility factors in cancer development. It is possible that DNA repair polymorphisms may also influence the risk of gene mutation. The 399Gln polymorphism in the DNA repair gene XRCC1 has been indicated to have a contributive role in DNA adduct formation, sister chromatid exchange, and an increased risk of cancer development. Two hundred thirty-seven male oral squamous cell carcinomas (OSCCs) were included in a study to investigate the role of the XRCC1 194Trp, 280His, and 399Gln polymorphisms on p53 gene mutation. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the conserved regions of the p53 gene (exons 5-9). The XRCC1 genotype was determined by PCR-RFLP. Nineteen (8.02%) of the 237 OSCCs had a Gln/Gln genotype. One hundred six (43.88%) of the 237 OSCCs showed p53 gene mutations at exons 5-9. The OSCC patients with a Gln/Gln genotype exhibited a significantly higher frequency of p53 mutation than those with an Arg/Gln and an Arg/Arg genotype. After adjustment for age, cigarette smoking, areca quid chewing, and alcohol drinking, the Gln/Gln genotype still showed an independent association with the frequency of p53 mutation (odd ratio, 4.50; 95% confidence interval, 1.52-13.36). The findings support the hypothesis that XRCC1 Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in a DNA repair deficiency. This study also suggests an important role for the XRCC1 399Gln polymorphism in p53 gene mutation in Taiwanese OSCCs.
Hsieh
Ling-Ling
LL
Department of Public Health, Chang Gung University, Tao-Yuan 333, Taiwan.
Chien
Huei-Tzu
HT
Chen
I-How
IH
Liao
Chun-Ta
CT
Wang
Hung-Ming
HM
Jung
Shih-Ming
SM
Wang
Pei-Feng
PF
Chang
Joseph Tung-Chieh
JT
Chen
Min-Chi
MC
Cheng
Ann-Joy
AJ
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D018736:DNA Adducts; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012854:Sister Chromatid Exchange; D013624:Taiwan / Q000453:epidemiology; D000076105:X-ray Repair Cross Complementing Protein 1
D018736:DNA Adducts; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human