Association of Genetic Variants of Enzymes Involved in Folate / One-Carbon Metabolism with Female Breast Cancer in Jordan

Jordan Journal of Biological Sciences

May F. Sadiq¹ 

关键词: Single nucleotide Polymorphism;    MTR;    MTHFR;    TYMS;    MTRR;    Breast cancer;    Jordan.;   

DOI  :  

学科分类：生物科学（综合）

来源: Hashemite University, Deanship of Research and Higher Studies

【 摘 要 】

Folate/one-carbon metabolism plays key roles in gene expression, and in the synthesis and repair of DNA. Therefore, it differently influences the pathogenesis of different diseases including cancer in different populations. This case-control study examined the association between the risks of female breast cancer with five functional single-nucleotide polymorphisms (SNPs) in the folate/one-carbon metabolism. These were MTR A2756G (rs1805087), MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), TYMS 1494 ins/del 6 (rs151264360) and MTRR A66G (rs1801394). This study included two-hundred female breast cancer cases and two-hundred age-matched female controls. The DNA samples were extracted from peripheral blood and were genotyped by PCR-RFLP. Comparisons between frequencies of alleles and genotypes in the different groups were evaluated using Pearson chi square test (P= 0.05), while the associations between each SNP and the risk of breast cancer were estimated by logistic regression analysis and calculation of odds ratios (OR) with 95 % confidence intervals (CI). Results showed that MTR 2756GG genotype is directly associated with breast cancer (OR = 4.360; CI= 1.213-15.666; P = 0.011), while its heterozygous genotype MTR 2756AG had no such risk, indicating that MTR 2756G allele is recessive to the wild type allele MTR 2756A in the whole group of cases, but is dominant in the post-menopausal cases. Besides, significant differences appeared in the distributions of both MTR 2756G allele (P = 0.022) and its genotypes (P = 0.008) between the pre- and post-menopausal cases respectively, which indicated for the first time, that the post-menopausal status affects the dominance of the polymorphism MTR A2756G as a risk factor for breast cancer. The results also showed that MTHFR C677T, TYMS 1494 ins/del 6 and MTRR A66G are strongly associated with breast cancer only when present in double compound heterozygous states (odd ratios between 2.6 and 6.7). In conclusion, folate/one-carbon metabolism contributes to the risk of female breast cancer in Jordan, and this contribution can be modified by the menopausal status of the females.

【 授权许可】

CC BY