caa a22 4500 463255895 CHVBK 20180405153355.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s00277-007-0350-2 doi (NATIONALLICENCE)springer-10.1007/s00277-007-0350-2 Genetic polymorphisms of methylenetetrahydrofolate reductase and promoter methylation of MGMT and FHIT genes in diffuse large B cell lymphoma risk in Middle East [Elektronische Daten] [Abdul Siraj, Muna Ibrahim, Maha Al-Rasheed, Rong Bu, Prashant Bavi, Zeenath Jehan, Jehad Abubaker, Walid Murad, Fouad Al-Dayel, Adnan Ezzat, Hassan El-Solh, Shahab Uddin, Khawla Al-Kuraya] Diffuse large B cell lymphoma (DLBCL) is one of the most common non-Hodgkin's lymphoma types. Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one carbon metabolism of deoxyribonucleic acid (DNA) synthesis and methylation; both are implicated in carcinogenesis of many types of cancer including lymphoma. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate as a cancer-predisposing factor. The O6 methylguanine DNA methyltransferase (MGMT) and fragile histidine triad (FHIT) genes are transcriptionally silenced by promoter hypermethylation in DLBCL. These genetic differences are highly race specific and have never been screened in the Saudi DLBCL patients. We conducted a hospital-based case-control study including 160 DLBCL cases and 511 Saudi control samples analyzing the MTHFR C677T and A1298C functional polymorphisms by the restriction fragment length polymorphism method and their association with MGMT and FHIT genes promoter hypermethylation. Our data demonstrated that Saudi individuals carrying MTHFR genotype 1298CC (p < 0.001) and the 1298C allele (p = 0.012) had 4.23 and 1.73-fold higher risk of developing DLBCL, respectively. Additionally, combined genotype CCCC (MTHFR 677CC + MTHFR 1298CC) was associated with 3.489-fold, and CTCC (MTHFR 677 CT + 1298CC) was related to 9.515-fold higher risk, compared with full MTHFR enzyme activity. No significant association between MTHFR variant genotypes and methylation of MGMT and FHIT genes were observed. Our findings suggested that polymorphisms of MTHFR enzyme genes might be associated with the individual susceptibility to develop DLBCL. Additionally, the results indicated that MTHFR variants were not related to MGMT or FHIT hypermethylation in DLBCL. Springer-Verlag, 2007 MTHFR nationallicence Diffuse large B cell lymphoma nationallicence MGMT nationallicence FHIT nationallicence Methylation nationallicence Siraj Abdul Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Ibrahim Muna Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Al-Rasheed Maha Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Bu Rong Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Bavi Prashant Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Jehan Zeenath Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Abubaker Jehad Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Murad Walid Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut Al-Dayel Fouad Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut Ezzat Adnan King Faisal Cancer Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut El-Solh Hassan Pediatric Hematology-Oncology, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Uddin Shahab Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Al-Kuraya Khawla Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut Annals of Hematology Springer-Verlag 86/12(2007-12-01), 887-895 0939-5555 86:12<887 2007 86 277 https://doi.org/10.1007/s00277-007-0350-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00277-007-0350-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Siraj Abdul Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Ibrahim Muna Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Al-Rasheed Maha Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Bu Rong Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Bavi Prashant Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Jehan Zeenath Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Abubaker Jehad Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Murad Walid Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Al-Dayel Fouad Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Ezzat Adnan King Faisal Cancer Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- El-Solh Hassan Pediatric Hematology-Oncology, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Uddin Shahab Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 700 1- Al-Kuraya Khawla Department of Human Cancer Genomic Research Centre, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia aut NATIONALLICENCE 773 0- Annals of Hematology Springer-Verlag 86/12(2007-12-01), 887-895 0939-5555 86:12<887 2007 86 277 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer