Association of MTHFR, MTR, MTRR, RFC1 and DHFR Gene Polymorphisms With Susceptibility to Sporadic Colon Cancer (CROSBI ID 169447)
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Jokić, Mladen ; Brčić-Kostić, Krunoslav ; Štefulj, Jasminka ; Catela Ivković, Tina ; Lončar, Božo ; Gamulin, Marija ; Kapitanović, Sanja
engleski
Association of MTHFR, MTR, MTRR, RFC1 and DHFR Gene Polymorphisms With Susceptibility to Sporadic Colon Cancer
Altered folate levels may play important role in colon carcinogenesis. The aim of this study was to investigate the association of polymorphisms in key folate-metabolizing genes with susceptibility to sporadic colon cancer. Six common polymorphisms (two in MTHFR and one in MTR, MTRR, RFC1 and DHFR genes) were genotyped in 300 healthy subjects and 300 colon cancer patients from Croatia. Obtained results indicate possible protective role of MTRR 66 AA in sporadic colon cancer (OR=0.655 ; 95%CI=0.441-0.973 ; p=0.04). Maximum-likelihood analysis of haplotypes revealed a LD between the two investigated polymorphisms of the MTHFR gene (C677T and A1298C), both in control and patient group (p<0.01 for both). LD was also detected between MTRR A66G and MTHFR A1298C polymorphisms but only in a group of patients (p<0.01). A haplotype of A66G and A1298C polymorphisms, A/A proved to be protective (OR=0.775 ; 95%CI=0.603-0.996 ; p=0.04) while haplotype A/G was risk factor for colon cancer (OR=1.270 ; 95%CI=1.007-1.602 ; p=0.04). Contrary to some previous studies, single locus analyses identified no polymorphisms associated with the risk for colon cancer, but demonstrated possible protective effect of MTRR 66 AA genotype. The detected significant LD between two loci (MTHFR A1298C and MTRR A66G) located on different chromosomes indicates a strong selective force as a mechanism for the maintenance of their linkage. Specific combinations of alleles of these two polymorphisms showed a protective but also a risk effect on colon cancer susceptibility.
polymorphisms; folate; colon cancer
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