Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study

Abstract

<b>Background:</b> Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNAfunction. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number ofhuman diseases, including cancer. <br/><b>Objective</b>: The association between MTHFR C677T and A1298C genotype andhaplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials and<br/><b>Methods</b>: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89controls taken from the general population, employing the PCR-RFLP technique. <br/><b>Results</b>: The frequency of thegenotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphismat this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3%among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likelyto have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CCgenotype were 9.9 and 6.7 times more likely to have LC, respectively (ORsmokers=9.9; 95%CI: 1.2-84.5, p=0.018;ORmen=6.6; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showeddifferential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotypewas associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). <br/><b>Conclusions</b>: Thegenetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele atposition 677) may modulate the risk for LC development among the Jordanian population. Risk associated withthe 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folatemetabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.