Association of the 609 C/T NAD(P)H: quinone oxidoreductase (NQO1) polymorphism with development of cutaneous malignant melanoma

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 C667T, 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 (Hayward, 2003). According to many studies done at this area, folate deficiency has been associated with chromosome strand breaks (Blount et al , 1997), impaired DNA repair (Hayward, 2003), DNA hypomethylation and hypermethylation all of which have been associated with cancer cell formation (Simonetta et al 2001) (Dong-Hyun K. 2007). 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Birmingham university and personal funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted from South Birmingham (UK) Local Research Ethics Committee (reference number 0534) before commencement of the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript * (CMM) : Cutaneous Malignant Melanoma (UV) : Ultraviolet (CDK) : cyclin dependent kinase (CDKI) : cyclin dependent kinase inhibitor (ROS) : reactive oxygen species (8-oxo dG) : 8-oxo 7,8-dihydro-2’-deoxyguanosine (OGG1) : 8 oxo deoxyguanosine DNA glycosylase 1 (NAT) : N-acetyl transferase (NQO1) : NAD(P)H: quinone oxidoreductase (GST) : glutathione-S-transferase (XRCC1) : X-ray repair complementing defective repair in Chinese hamster cells 1