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>T and MTHFR 1298A>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.