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Genetic instability resulting from mutations in repair genes, defects in folic acid metabolism or DNA synthesis has been reported to contribute significantly to the development of skin cancer. The enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are essential participants in folic acid metabolism and DNA synthesis. Thus, the present case-control study was conducted to determine whether an association exists between the MTHFR/TS polymorphisms and squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) among Korean individuals. The study subjects comprised 95 patients with SCC, 100 patients with BCC and 207 controls with no evidence of malignancy or pre-malignant lesions. Patients with skin cancer and control samples were analyzed for polymorphisms of the MTHFR or TS genes by means of polymerase chain reaction-restriction fragment length polymorphism. The MTHFR 677C&gt;T and MTHFR 1298A&gt;C polymorphisms showed no significance with regard to the development of SCC and BCC. However, within the 6 bp insertion (ins)/deletion (del) polymorphism in the 3'-untranslated region (3'-UTR) of the TS gene, the BCC group showed statistical significance with a 2.8-fold increased risk of cancer development [adjusted odds ratio (AOR)=2.821] in heterozygous mutations (0 bp/6 bp), 7.5-fold (AOR=7.539) in homozygous mutations (6 bp/6 bp) and 3-fold (AOR=3.079) upon combination of heterozygous mutations and homozygous mutations (0 bp/6 bp + 6 bp/6 bp). We thus conclude that the 6 bp ins/del polymorphism in the 3'-UTR is associated with increased risk of the development of skin cancer among Korean individuals with BCC.

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase in squamous cell carcinoma and basal cell carcinoma of the skin