Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia
Background and Purpose : ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia are unknown and are likely to involve an interaction between genetic and environmental factors. Therefore, unfavourable gene-environmental interactions might be involved in the ge...
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| creator | Kamil, Azzah Musa, Hibah S. Ubayd, Jamal T. Bu, Rong R. Bhatia, Kishor G. |
| description | Background and Purpose : ALL is the most common
pediatric cancer. The causes of the majority of pediatric
acute leukemia are unknown and are likely to involve an
interaction between genetic and environmental factors.
Therefore, unfavourable gene-environmental interactions
might be involved in the genesis of ALL. The aim of this
work was to evaluate, in a case-control study, whether the
common polymorphisms in 5, 10-methylenetetrahydrofolate
reductase (MTHFR) namely (C677T and A1298C)
and methionine synthase (MS) (A2756G) genes may play
a role in altering susceptibility to pediatric ALL as individual
genes and in combination.
Patients and Methods: DNA of 88 ALL patients (age
£18 years) and 311 healthy control subjects was analyzed
for the polymorphisms of MTHFR and MS genes using
PCR-RFLP method.
Results: The frequencies of the wild types of MTHFR
677CC, MTHFR 1298AA and MS 2756AA, the homozygous
genotypes of MTHFR 677TT, MTHFR 1298CC and
MS 2756GG and heterozygous genotypes of MTHFR
677CT and MS 2756AG showed no statistically significant
differences between patients and controls. The frequency
of the MTHFR 1298AC heterozygous genotype was 25%
among patients compared to 45.0% among controls; the
difference was found to be statistically significant (p value
=0.001, O.R=0.382 & 95% C.I=0.222-0.658).
The frequency of the MTHFR1298AC heterozygous
genotype plus 1298CC homozygous genotype was 34%
among patients compared to 54.3% among controls and
the difference was statistically significant (p value=0.001).
A synergistic effect of 677CT and1298AC (CTAC) was
observed, (p value=0.002) with 3.65 fold protection (OR
0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for
MTHFR 1298AC alone. This protective effect of CTAC polymorphism was abolished when combined with MS
2756AA or AG.
Conclusion: The present study provided further evidence
for the protective role of MTHFR 1298AC mutant
alleles in acute lymphoblastic leukemia in children (2.6
fold protection). This suggests that folate and methionine
metabolism play an important role in the pathogenesis of
pediatric ALL. In contrast to the main bulk of literature,
we did not find any protective role of either MTHFR
C677T or MS A2756G polymorphisms. This may reflect
the ethnic variation in both the polymorphism frequencies,
variation in plasma level of folate, in addition to the
possible role of gene-environment interaction mainly
dietary availability of folate. The synergistic effect of
MTHFR 1298AC and 677CT and its abol |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_70142828</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70142828</sourcerecordid><originalsourceid>FETCH-LOGICAL-e145t-b687637996b2b3e86b8fa9201934bee4c13142e3ec6a60458057bc04f5a700b3</originalsourceid><addsrcrecordid>eNo9kMFOwzAMhisEYmPwBgjlhOBQKWnatD2iigHSEBLsPjmtQ8PapSTpoW_C4xLY4GTL-vz7_30UzZko8rgsS3EcesZoTLlIZtGZcx-UCkHz7DSasZLylPNyHn29TTu079p5XRNUCmtPjCI9-nbqPHoL7dRYo0wHHonFZqw9OCQ3z-vH5estqUSerwnsGgIsKYuKDKabemOHVruegCNWuy3pTaOVRut-tAdsNHgb7kE9BtHAD62RHfx66HDcYq_hPDpR0Dm8ONRFtF7er6vHePXy8FTdrWJkaeZjGeIKnoe8MpEcCyELBWVCWclTiZjWjLM0QY61AEHTrKBZLmuaqgxySiVfRNd72cGazxGd3_Ta1dh1sEMzuk1Ow3qRFAG8OoCj7LHZDFb3YKfN3ysDcLkHMMxRwT-RFMEP_wYyWnvd</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70142828</pqid></control><display><type>article</type><title>Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Kamil, Azzah ; Musa, Hibah S. ; Ubayd, Jamal T. ; Bu, Rong R. ; Bhatia, Kishor G.</creator><creatorcontrib>Kamil, Azzah ; Musa, Hibah S. ; Ubayd, Jamal T. ; Bu, Rong R. ; Bhatia, Kishor G.</creatorcontrib><description>Background and Purpose : ALL is the most common
pediatric cancer. The causes of the majority of pediatric
acute leukemia are unknown and are likely to involve an
interaction between genetic and environmental factors.
Therefore, unfavourable gene-environmental interactions
might be involved in the genesis of ALL. The aim of this
work was to evaluate, in a case-control study, whether the
common polymorphisms in 5, 10-methylenetetrahydrofolate
reductase (MTHFR) namely (C677T and A1298C)
and methionine synthase (MS) (A2756G) genes may play
a role in altering susceptibility to pediatric ALL as individual
genes and in combination.
Patients and Methods: DNA of 88 ALL patients (age
£18 years) and 311 healthy control subjects was analyzed
for the polymorphisms of MTHFR and MS genes using
PCR-RFLP method.
Results: The frequencies of the wild types of MTHFR
677CC, MTHFR 1298AA and MS 2756AA, the homozygous
genotypes of MTHFR 677TT, MTHFR 1298CC and
MS 2756GG and heterozygous genotypes of MTHFR
677CT and MS 2756AG showed no statistically significant
differences between patients and controls. The frequency
of the MTHFR 1298AC heterozygous genotype was 25%
among patients compared to 45.0% among controls; the
difference was found to be statistically significant (p value
=0.001, O.R=0.382 & 95% C.I=0.222-0.658).
The frequency of the MTHFR1298AC heterozygous
genotype plus 1298CC homozygous genotype was 34%
among patients compared to 54.3% among controls and
the difference was statistically significant (p value=0.001).
A synergistic effect of 677CT and1298AC (CTAC) was
observed, (p value=0.002) with 3.65 fold protection (OR
0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for
MTHFR 1298AC alone. This protective effect of CTAC polymorphism was abolished when combined with MS
2756AA or AG.
Conclusion: The present study provided further evidence
for the protective role of MTHFR 1298AC mutant
alleles in acute lymphoblastic leukemia in children (2.6
fold protection). This suggests that folate and methionine
metabolism play an important role in the pathogenesis of
pediatric ALL. In contrast to the main bulk of literature,
we did not find any protective role of either MTHFR
C677T or MS A2756G polymorphisms. This may reflect
the ethnic variation in both the polymorphism frequencies,
variation in plasma level of folate, in addition to the
possible role of gene-environment interaction mainly
dietary availability of folate. The synergistic effect of
MTHFR 1298AC and 677CT and its abolishment by MS
2756AA or AG further emphasizes that the interaction of
genes, rather than the polymorphism in any single one,
determines risk susceptibility to disease.</description><identifier>ISSN: 1110-0362</identifier><identifier>EISSN: 1687-9996</identifier><identifier>PMID: 19034339</identifier><language>eng</language><publisher>Cairo, Egypt: Cairo University, National Cancer Institute</publisher><subject>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics ; Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; DNA Mutational Analysis ; DNA, Neoplasm - genetics ; Female ; Genetic polymorphisms ; Genotype ; Heterozygote ; Homozygote ; Humans ; Leukemia in children ; Lymphoblastic leukemia in children ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Retrospective Studies ; Risk Factors ; ابيضاض الدم الليمفاوي الحاد ; الأطفال ; السرطان ; سرطان الدم</subject><ispartof>Journal of Egyptian National Cancer Institute, 2007-06, Vol.19 (2), p.96-105</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19034339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kamil, Azzah</creatorcontrib><creatorcontrib>Musa, Hibah S.</creatorcontrib><creatorcontrib>Ubayd, Jamal T.</creatorcontrib><creatorcontrib>Bu, Rong R.</creatorcontrib><creatorcontrib>Bhatia, Kishor G.</creatorcontrib><title>Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia</title><title>Journal of Egyptian National Cancer Institute</title><addtitle>J Egypt Natl Canc Inst</addtitle><description>Background and Purpose : ALL is the most common
pediatric cancer. The causes of the majority of pediatric
acute leukemia are unknown and are likely to involve an
interaction between genetic and environmental factors.
Therefore, unfavourable gene-environmental interactions
might be involved in the genesis of ALL. The aim of this
work was to evaluate, in a case-control study, whether the
common polymorphisms in 5, 10-methylenetetrahydrofolate
reductase (MTHFR) namely (C677T and A1298C)
and methionine synthase (MS) (A2756G) genes may play
a role in altering susceptibility to pediatric ALL as individual
genes and in combination.
Patients and Methods: DNA of 88 ALL patients (age
£18 years) and 311 healthy control subjects was analyzed
for the polymorphisms of MTHFR and MS genes using
PCR-RFLP method.
Results: The frequencies of the wild types of MTHFR
677CC, MTHFR 1298AA and MS 2756AA, the homozygous
genotypes of MTHFR 677TT, MTHFR 1298CC and
MS 2756GG and heterozygous genotypes of MTHFR
677CT and MS 2756AG showed no statistically significant
differences between patients and controls. The frequency
of the MTHFR 1298AC heterozygous genotype was 25%
among patients compared to 45.0% among controls; the
difference was found to be statistically significant (p value
=0.001, O.R=0.382 & 95% C.I=0.222-0.658).
The frequency of the MTHFR1298AC heterozygous
genotype plus 1298CC homozygous genotype was 34%
among patients compared to 54.3% among controls and
the difference was statistically significant (p value=0.001).
A synergistic effect of 677CT and1298AC (CTAC) was
observed, (p value=0.002) with 3.65 fold protection (OR
0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for
MTHFR 1298AC alone. This protective effect of CTAC polymorphism was abolished when combined with MS
2756AA or AG.
Conclusion: The present study provided further evidence
for the protective role of MTHFR 1298AC mutant
alleles in acute lymphoblastic leukemia in children (2.6
fold protection). This suggests that folate and methionine
metabolism play an important role in the pathogenesis of
pediatric ALL. In contrast to the main bulk of literature,
we did not find any protective role of either MTHFR
C677T or MS A2756G polymorphisms. This may reflect
the ethnic variation in both the polymorphism frequencies,
variation in plasma level of folate, in addition to the
possible role of gene-environment interaction mainly
dietary availability of folate. The synergistic effect of
MTHFR 1298AC and 677CT and its abolishment by MS
2756AA or AG further emphasizes that the interaction of
genes, rather than the polymorphism in any single one,
determines risk susceptibility to disease.</description><subject>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</subject><subject>Adolescent</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Neoplasm - genetics</subject><subject>Female</subject><subject>Genetic polymorphisms</subject><subject>Genotype</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Leukemia in children</subject><subject>Lymphoblastic leukemia in children</subject><subject>Male</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>ابيضاض الدم الليمفاوي الحاد</subject><subject>الأطفال</subject><subject>السرطان</subject><subject>سرطان الدم</subject><issn>1110-0362</issn><issn>1687-9996</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMFOwzAMhisEYmPwBgjlhOBQKWnatD2iigHSEBLsPjmtQ8PapSTpoW_C4xLY4GTL-vz7_30UzZko8rgsS3EcesZoTLlIZtGZcx-UCkHz7DSasZLylPNyHn29TTu079p5XRNUCmtPjCI9-nbqPHoL7dRYo0wHHonFZqw9OCQ3z-vH5estqUSerwnsGgIsKYuKDKabemOHVruegCNWuy3pTaOVRut-tAdsNHgb7kE9BtHAD62RHfx66HDcYq_hPDpR0Dm8ONRFtF7er6vHePXy8FTdrWJkaeZjGeIKnoe8MpEcCyELBWVCWclTiZjWjLM0QY61AEHTrKBZLmuaqgxySiVfRNd72cGazxGd3_Ta1dh1sEMzuk1Ow3qRFAG8OoCj7LHZDFb3YKfN3ysDcLkHMMxRwT-RFMEP_wYyWnvd</recordid><startdate>200706</startdate><enddate>200706</enddate><creator>Kamil, Azzah</creator><creator>Musa, Hibah S.</creator><creator>Ubayd, Jamal T.</creator><creator>Bu, Rong R.</creator><creator>Bhatia, Kishor G.</creator><general>Cairo University, National Cancer Institute</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200706</creationdate><title>Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia</title><author>Kamil, Azzah ; Musa, Hibah S. ; Ubayd, Jamal T. ; Bu, Rong R. ; Bhatia, Kishor G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e145t-b687637996b2b3e86b8fa9201934bee4c13142e3ec6a60458057bc04f5a700b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</topic><topic>Adolescent</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Neoplasm - genetics</topic><topic>Female</topic><topic>Genetic polymorphisms</topic><topic>Genotype</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Leukemia in children</topic><topic>Lymphoblastic leukemia in children</topic><topic>Male</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>ابيضاض الدم الليمفاوي الحاد</topic><topic>الأطفال</topic><topic>السرطان</topic><topic>سرطان الدم</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kamil, Azzah</creatorcontrib><creatorcontrib>Musa, Hibah S.</creatorcontrib><creatorcontrib>Ubayd, Jamal T.</creatorcontrib><creatorcontrib>Bu, Rong R.</creatorcontrib><creatorcontrib>Bhatia, Kishor G.</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Egyptian National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kamil, Azzah</au><au>Musa, Hibah S.</au><au>Ubayd, Jamal T.</au><au>Bu, Rong R.</au><au>Bhatia, Kishor G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia</atitle><jtitle>Journal of Egyptian National Cancer Institute</jtitle><addtitle>J Egypt Natl Canc Inst</addtitle><date>2007-06</date><risdate>2007</risdate><volume>19</volume><issue>2</issue><spage>96</spage><epage>105</epage><pages>96-105</pages><issn>1110-0362</issn><eissn>1687-9996</eissn><abstract>Background and Purpose : ALL is the most common
pediatric cancer. The causes of the majority of pediatric
acute leukemia are unknown and are likely to involve an
interaction between genetic and environmental factors.
Therefore, unfavourable gene-environmental interactions
might be involved in the genesis of ALL. The aim of this
work was to evaluate, in a case-control study, whether the
common polymorphisms in 5, 10-methylenetetrahydrofolate
reductase (MTHFR) namely (C677T and A1298C)
and methionine synthase (MS) (A2756G) genes may play
a role in altering susceptibility to pediatric ALL as individual
genes and in combination.
Patients and Methods: DNA of 88 ALL patients (age
£18 years) and 311 healthy control subjects was analyzed
for the polymorphisms of MTHFR and MS genes using
PCR-RFLP method.
Results: The frequencies of the wild types of MTHFR
677CC, MTHFR 1298AA and MS 2756AA, the homozygous
genotypes of MTHFR 677TT, MTHFR 1298CC and
MS 2756GG and heterozygous genotypes of MTHFR
677CT and MS 2756AG showed no statistically significant
differences between patients and controls. The frequency
of the MTHFR 1298AC heterozygous genotype was 25%
among patients compared to 45.0% among controls; the
difference was found to be statistically significant (p value
=0.001, O.R=0.382 & 95% C.I=0.222-0.658).
The frequency of the MTHFR1298AC heterozygous
genotype plus 1298CC homozygous genotype was 34%
among patients compared to 54.3% among controls and
the difference was statistically significant (p value=0.001).
A synergistic effect of 677CT and1298AC (CTAC) was
observed, (p value=0.002) with 3.65 fold protection (OR
0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for
MTHFR 1298AC alone. This protective effect of CTAC polymorphism was abolished when combined with MS
2756AA or AG.
Conclusion: The present study provided further evidence
for the protective role of MTHFR 1298AC mutant
alleles in acute lymphoblastic leukemia in children (2.6
fold protection). This suggests that folate and methionine
metabolism play an important role in the pathogenesis of
pediatric ALL. In contrast to the main bulk of literature,
we did not find any protective role of either MTHFR
C677T or MS A2756G polymorphisms. This may reflect
the ethnic variation in both the polymorphism frequencies,
variation in plasma level of folate, in addition to the
possible role of gene-environment interaction mainly
dietary availability of folate. The synergistic effect of
MTHFR 1298AC and 677CT and its abolishment by MS
2756AA or AG further emphasizes that the interaction of
genes, rather than the polymorphism in any single one,
determines risk susceptibility to disease.</abstract><cop>Cairo, Egypt</cop><pub>Cairo University, National Cancer Institute</pub><pmid>19034339</pmid><tpages>10</tpages></addata></record> |
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| ispartof | Journal of Egyptian National Cancer Institute, 2007-06, Vol.19 (2), p.96-105 |
| issn | 1110-0362 1687-9996 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics Adolescent Case-Control Studies Child Child, Preschool DNA Mutational Analysis DNA, Neoplasm - genetics Female Genetic polymorphisms Genotype Heterozygote Homozygote Humans Leukemia in children Lymphoblastic leukemia in children Male Methylenetetrahydrofolate Reductase (NADPH2) - genetics Polymerase Chain Reaction Polymorphism, Genetic - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Retrospective Studies Risk Factors ابيضاض الدم الليمفاوي الحاد الأطفال السرطان سرطان الدم |
| title | Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and a1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia |
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