Biologie und Medizin

Abstrakt

Association of the 609 C/T NAD(P)H: Quinone Oxidoreductase (NQO1) Polymorphism with Development of Cutaneous Malignant Melanoma

Adam Towler, Amanda J Lee, Jerry Marsden, Joanna Norman, Ryan Doran, Rhiannon M David, Anne E Pheasant, James K Chipman, Maryam Naghynajadfard*, Nikolas J Hodges

Cutaneous Malignant Melanoma (CMM) is a life threatening disease whose incidence and mortality rates have risen rapidly in the White Caucasian population in recent decades. The aim of the current study was to investigate the association between polymorphisms in genes involved in DNA-repair and detoxification of reactive metabolites and the development of CMM. The patient cohort consisted of 69 individuals while the control population consisted of 100 individuals. We found a statistically significant association between the presence of the wild type NQO1 C allele, MDHFR C T, TS 1494del6, TSER polymorphisms and development of CMM (P=0.04; odds ratio=2.35). The NQO1 CC genotype was more strongly associated with CMM development (P=0.016; odds ratio=2.92). The NQO1 gene codes for a protein that has been widely considered to be protective through its ability to detoxify quinones. However recent studies have also linked it to an important source of reactive oxygen and to NF-κB-dependent proliferation of cultured melanoma cells. In conclusion these results link molecular epidemiology and experimental evidence for the role of the NQO1 gene product in development of CMM. MDHFR and TS in Folic acid metabolism are responsible for methylation of methyl group. Two important roles of folate ‘related to this study’ are the conversion of homocysteine to methionine and the generation of Thymidylate (dTMP) which is required for DNA synthesis. According to many studies done at this area, folate deficiency has been associated with chromosome strand breaks, impaired DNA repair, DNA hypomethylation and hypermethylation all of which have been associated with cancer cell formation. The result of study shows, MTHFR C677T and TS 6bp deletion/insertion are not related to increased risk of CMM and therefore have no effect on an individual’s susceptibility