Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia : a case-control study
We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR)...
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| Veröffentlicht in: | Leukemia 2007-02, Vol.21 (2), p.320-325 |
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| creator | GAST, A BERMEJO, J. L FLOHR, T STANULLA, M BURWINKEL, B SCHRAPPE, M BARTRAM, C. R HEMMINKI, K KUMAR, R |
| description | We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global PG and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk. |
| doi_str_mv | 10.1038/sj.leu.2404474 |
| format | Article |
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L ; FLOHR, T ; STANULLA, M ; BURWINKEL, B ; SCHRAPPE, M ; BARTRAM, C. R ; HEMMINKI, K ; KUMAR, R</creator><creatorcontrib>GAST, A ; BERMEJO, J. L ; FLOHR, T ; STANULLA, M ; BURWINKEL, B ; SCHRAPPE, M ; BARTRAM, C. R ; HEMMINKI, K ; KUMAR, R</creatorcontrib><description>We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2404474</identifier><identifier>PMID: 17136115</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Adolescent ; Adult ; Base Sequence ; Biological and medical sciences ; Cancer research ; Care and treatment ; Case-Control Studies ; Child ; Child, Preschool ; Childhood ; Children ; Confidence intervals ; DNA, Neoplasm - genetics ; Enzymes ; Epidemiology ; Female ; Folic acid ; Folic Acid - genetics ; Folic Acid - metabolism ; Gene polymorphism ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genetic testing ; Genotype ; Genotype & phenotype ; Haplotypes ; Health aspects ; Health risks ; Hematologic and hematopoietic diseases ; Homocysteine ; Humans ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphatic leukemia ; Male ; Medical research ; Medical sciences ; Metabolic pathways ; Metabolism ; Methyltransferase ; Morphology ; MtrR gene ; Odds Ratio ; Polymorphism ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Reductases ; Reference Values ; Risk analysis ; Risk management ; Statistical analysis ; Vitamin B</subject><ispartof>Leukemia, 2007-02, Vol.21 (2), p.320-325</ispartof><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c645t-a026f1e1c28d7c285acc8eb6353bb182dc775108715377c2df1290b1f88238493</citedby><cites>FETCH-LOGICAL-c645t-a026f1e1c28d7c285acc8eb6353bb182dc775108715377c2df1290b1f88238493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18534517$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17136115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GAST, A</creatorcontrib><creatorcontrib>BERMEJO, J. L</creatorcontrib><creatorcontrib>FLOHR, T</creatorcontrib><creatorcontrib>STANULLA, M</creatorcontrib><creatorcontrib>BURWINKEL, B</creatorcontrib><creatorcontrib>SCHRAPPE, M</creatorcontrib><creatorcontrib>BARTRAM, C. R</creatorcontrib><creatorcontrib>HEMMINKI, K</creatorcontrib><creatorcontrib>KUMAR, R</creatorcontrib><title>Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia : a case-control study</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cancer research</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Childhood</subject><subject>Children</subject><subject>Confidence intervals</subject><subject>DNA, Neoplasm - genetics</subject><subject>Enzymes</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - genetics</subject><subject>Folic Acid - metabolism</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genetic testing</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Homocysteine</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. 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The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). 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| subjects | Acute lymphoblastic leukemia Acute lymphocytic leukemia Adolescent Adult Base Sequence Biological and medical sciences Cancer research Care and treatment Case-Control Studies Child Child, Preschool Childhood Children Confidence intervals DNA, Neoplasm - genetics Enzymes Epidemiology Female Folic acid Folic Acid - genetics Folic Acid - metabolism Gene polymorphism Genes Genetic aspects Genetic polymorphisms Genetic testing Genotype Genotype & phenotype Haplotypes Health aspects Health risks Hematologic and hematopoietic diseases Homocysteine Humans Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphatic leukemia Male Medical research Medical sciences Metabolic pathways Metabolism Methyltransferase Morphology MtrR gene Odds Ratio Polymorphism Polymorphism, Genetic Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Reductases Reference Values Risk analysis Risk management Statistical analysis Vitamin B |
| title | Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia : a case-control study |
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