Analysis of cytochrome P450 2A6 polymorphism in oral cancer by High Resolution Melting

Autor: Chi-Yuan Chang, 張啟源
Rok vydání: 2011
Druh dokumentu: 學位論文 ; thesis
Popis: 99
ACKGROUND:CYP is now widely known as a family of enzymes metabolizing a wide variety of xenobiotics, including drugs and carcinogens. Human cytochrome P450 2A6(CYP2A6) is an important member of the CYPs and CYP2A6 has been reported that associated with risk of cancer Oral squamous cell carcinoma(OSCC) is one of the high lethality in Taiwan, to discover the cancer appear at the early year, we extremely need a fast, convenient and cheap way to screen OSCC. High Resolution Melting Analysis(HRMA) detect and distinguish wild type homozygote, heterozygote and mutative homozygote by fluorescence differ at the melting temperature. Material and Method:DNA sample from peripheral blood of 60 normal men and 55 OSCC patient/men, analysis the genotype and allele frequency by Q-PCR and HRMA. This is the first time to to analyze the CYP2A6 polymorphism by HRMA. Results:Genotype of CYP2A6, CYP2A6*1A/CYP2A6*1A, CYP2A6*1A/CYP2A6*1B, CYP2A6*1A/CYP2A6*5, CYP2A6*1A/CYP2A6*7, CYP2A6*1A/CYP2A6*9, CYP2A6*1B/CYP2A6*1B, CYP2A6*1B/CYP2A6*5, CYP2A6*1B/CYP2A6*7, CYP2A6*1B/CYP2A6*9, CYP2A6*5/CYP2A6*9, CYP2A6*9/CYP2A6*9, and allele of CYP2A6 were deteced. The frequency with which the subjects carried homozygotes of the CYP2A6* 9 which causes lack of the enzyme activity, was lower in the OSCC patients than in the healthy control subjects. The odds ratio (OR) of the group homozygous for the CYP2A6* 9 was significantly lower and calculated to be 0.08 (95% CI; 0.01–0.77) when the OR for the population with homozygotes ofthe CYP2A6 wild-type gene was defined as 1.00. In the allelic-base analysis, there was also a significant decrease in the OR for the CYP2A6*9 allele. Conclusion: A new and fast way to detect the group with high risk of OSCC and we suggest that CYP2A6* 9/ CYP2A6* 9 play an important role to decrease the risk of OSCC
Databáze: Networked Digital Library of Theses & Dissertations