Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA
Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level o...
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| Veröffentlicht in: | Cancer science 2012-12, Vol.103 (12), p.2159-2164 |
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| creator | Ono, Hiroe Iwasaki, Motoki Kuchiba, Aya Kasuga, Yoshio Yokoyama, Shiro Onuma, Hiroshi Nishimura, Hideki Kusama, Ritsu Ohnami, Sumiko Sakamoto, Hiromi Yoshida, Teruhiko Tsugane, Shoichiro |
| description | Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross‐sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03–0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females. |
| doi_str_mv | 10.1111/cas.12013 |
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As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross‐sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03–0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.12013</identifier><identifier>PMID: 22957669</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>5-Methyltetrahydrofolate-homocysteine S-methyltransferase ; Adult ; Age ; Aged ; Alcohol use ; Blood ; Breast cancer ; Cancer ; Carbon ; Carbon - metabolism ; Case-Control Studies ; Cross-Sectional Studies ; Deoxyribonucleic acid ; Diet ; Dietary intake ; DNA ; DNA biosynthesis ; DNA Methylation ; Drinking behavior ; Enzymes ; Epigenetics ; Ethanol ; Female ; Folic acid ; Folic Acid - administration & dosage ; Food ; Genetic factors ; Genetic Predisposition to Disease ; Genetic testing ; Health care ; Humans ; Inventories ; Leukocytes ; Leukocytes - metabolism ; Metabolism ; Methionine ; Methylenetetrahydrofolate reductase ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism ; Original ; Peripheral blood ; Polymorphism, Single Nucleotide ; Questionnaires ; Regression analysis ; Single-nucleotide polymorphism ; Standard deviation ; Statistical analysis ; Studies ; Vitamin B ; Vitamin B 12 - administration & dosage ; Vitamin B 6 - administration & dosage ; Vitamin B12 ; Vitamin B6 ; Vitamins ; Vitamins - administration & dosage</subject><ispartof>Cancer science, 2012-12, Vol.103 (12), p.2159-2164</ispartof><rights>2012 Japanese Cancer Association</rights><rights>2012 Japanese Cancer Association.</rights><rights>Copyright John Wiley & Sons, Inc. Dec 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5003-45a0dd57b0ad29f185463e66c4a2df2afc3969f502871d24f17fb34b5cf51e833</citedby><cites>FETCH-LOGICAL-c5003-45a0dd57b0ad29f185463e66c4a2df2afc3969f502871d24f17fb34b5cf51e833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659348/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659348/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,11560,27922,27923,45572,45573,46050,46474,53789,53791</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fcas.12013$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22957669$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ono, Hiroe</creatorcontrib><creatorcontrib>Iwasaki, Motoki</creatorcontrib><creatorcontrib>Kuchiba, Aya</creatorcontrib><creatorcontrib>Kasuga, Yoshio</creatorcontrib><creatorcontrib>Yokoyama, Shiro</creatorcontrib><creatorcontrib>Onuma, Hiroshi</creatorcontrib><creatorcontrib>Nishimura, Hideki</creatorcontrib><creatorcontrib>Kusama, Ritsu</creatorcontrib><creatorcontrib>Ohnami, Sumiko</creatorcontrib><creatorcontrib>Sakamoto, Hiromi</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Tsugane, Shoichiro</creatorcontrib><title>Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross‐sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03–0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females.</description><subject>5-Methyltetrahydrofolate-homocysteine S-methyltransferase</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Alcohol use</subject><subject>Blood</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Carbon</subject><subject>Carbon - metabolism</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Deoxyribonucleic acid</subject><subject>Diet</subject><subject>Dietary intake</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA Methylation</subject><subject>Drinking behavior</subject><subject>Enzymes</subject><subject>Epigenetics</subject><subject>Ethanol</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - administration & dosage</subject><subject>Food</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic testing</subject><subject>Health care</subject><subject>Humans</subject><subject>Inventories</subject><subject>Leukocytes</subject><subject>Leukocytes - metabolism</subject><subject>Metabolism</subject><subject>Methionine</subject><subject>Methylenetetrahydrofolate reductase</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - metabolism</subject><subject>Original</subject><subject>Peripheral blood</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Questionnaires</subject><subject>Regression analysis</subject><subject>Single-nucleotide polymorphism</subject><subject>Standard deviation</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Vitamin B</subject><subject>Vitamin B 12 - administration & dosage</subject><subject>Vitamin B 6 - administration & dosage</subject><subject>Vitamin B12</subject><subject>Vitamin B6</subject><subject>Vitamins</subject><subject>Vitamins - administration & dosage</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkc1qFTEUxwdRbK0ufAEJuKmLafM5udkIl-snFF2o65DJnNybmpnUJLflggsfwWf0Sczt1KKCYDYJyS8_zjn_pnlM8Amp69SafEIoJuxOc0gYV63EuLt7fZatwoweNA9yPseYdVzx-80BpUrIrlOHzddlztF6U3ycUHRo8FBM2iEzDWgNExRvkTO2xJRRgmAKDKhEFCf48e27Namv38b6pY_B5xFd-bJB6xB7E_bXm12YzQEuIez9Abafo90VQC_eLR8295wJGR7d7EfNp1cvP67etGfvX79dLc9aK2rNLRcGD4OQPTYDVY4sBO8YdJ3lhg6OGmeZ6pQTmC4kGSh3RLqe8V5YJwgsGDtqns_ei20_wmBhKskEfZH8WHvV0Xj958vkN3odL7XshGJ8UQXHN4IUv2whFz36bCEEM0HcZk2okFLyOtL_QCnjDEuqKvr0L_Q8btNUJ6EpU0pUFO-LfzZTNsWcE7jbugnW-_h1jV9fx1_ZJ783ekv-yrsCpzNw5QPs_m3Sq-WHWfkT_9676g</recordid><startdate>201212</startdate><enddate>201212</enddate><creator>Ono, Hiroe</creator><creator>Iwasaki, Motoki</creator><creator>Kuchiba, Aya</creator><creator>Kasuga, Yoshio</creator><creator>Yokoyama, Shiro</creator><creator>Onuma, Hiroshi</creator><creator>Nishimura, Hideki</creator><creator>Kusama, Ritsu</creator><creator>Ohnami, Sumiko</creator><creator>Sakamoto, Hiromi</creator><creator>Yoshida, Teruhiko</creator><creator>Tsugane, Shoichiro</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>5PM</scope></search><sort><creationdate>201212</creationdate><title>Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA</title><author>Ono, Hiroe ; Iwasaki, Motoki ; Kuchiba, Aya ; Kasuga, Yoshio ; Yokoyama, Shiro ; Onuma, Hiroshi ; Nishimura, Hideki ; Kusama, Ritsu ; Ohnami, Sumiko ; Sakamoto, Hiromi ; Yoshida, Teruhiko ; Tsugane, Shoichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5003-45a0dd57b0ad29f185463e66c4a2df2afc3969f502871d24f17fb34b5cf51e833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>5-Methyltetrahydrofolate-homocysteine S-methyltransferase</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Alcohol use</topic><topic>Blood</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Carbon</topic><topic>Carbon - metabolism</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Deoxyribonucleic acid</topic><topic>Diet</topic><topic>Dietary intake</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA Methylation</topic><topic>Drinking behavior</topic><topic>Enzymes</topic><topic>Epigenetics</topic><topic>Ethanol</topic><topic>Female</topic><topic>Folic acid</topic><topic>Folic Acid - administration & dosage</topic><topic>Food</topic><topic>Genetic factors</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic testing</topic><topic>Health care</topic><topic>Humans</topic><topic>Inventories</topic><topic>Leukocytes</topic><topic>Leukocytes - metabolism</topic><topic>Metabolism</topic><topic>Methionine</topic><topic>Methylenetetrahydrofolate reductase</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - metabolism</topic><topic>Original</topic><topic>Peripheral blood</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Questionnaires</topic><topic>Regression analysis</topic><topic>Single-nucleotide polymorphism</topic><topic>Standard deviation</topic><topic>Statistical analysis</topic><topic>Studies</topic><topic>Vitamin B</topic><topic>Vitamin B 12 - administration & dosage</topic><topic>Vitamin B 6 - administration & dosage</topic><topic>Vitamin B12</topic><topic>Vitamin B6</topic><topic>Vitamins</topic><topic>Vitamins - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ono, Hiroe</creatorcontrib><creatorcontrib>Iwasaki, Motoki</creatorcontrib><creatorcontrib>Kuchiba, Aya</creatorcontrib><creatorcontrib>Kasuga, Yoshio</creatorcontrib><creatorcontrib>Yokoyama, Shiro</creatorcontrib><creatorcontrib>Onuma, Hiroshi</creatorcontrib><creatorcontrib>Nishimura, Hideki</creatorcontrib><creatorcontrib>Kusama, Ritsu</creatorcontrib><creatorcontrib>Ohnami, Sumiko</creatorcontrib><creatorcontrib>Sakamoto, Hiromi</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Tsugane, Shoichiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Ono, Hiroe</au><au>Iwasaki, Motoki</au><au>Kuchiba, Aya</au><au>Kasuga, Yoshio</au><au>Yokoyama, Shiro</au><au>Onuma, Hiroshi</au><au>Nishimura, Hideki</au><au>Kusama, Ritsu</au><au>Ohnami, Sumiko</au><au>Sakamoto, Hiromi</au><au>Yoshida, Teruhiko</au><au>Tsugane, Shoichiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2012-12</date><risdate>2012</risdate><volume>103</volume><issue>12</issue><spage>2159</spage><epage>2164</epage><pages>2159-2164</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross‐sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03–0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>22957669</pmid><doi>10.1111/cas.12013</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2012-12, Vol.103 (12), p.2159-2164 |
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| source | Wiley-Blackwell Open Access Titles |
| subjects | 5-Methyltetrahydrofolate-homocysteine S-methyltransferase Adult Age Aged Alcohol use Blood Breast cancer Cancer Carbon Carbon - metabolism Case-Control Studies Cross-Sectional Studies Deoxyribonucleic acid Diet Dietary intake DNA DNA biosynthesis DNA Methylation Drinking behavior Enzymes Epigenetics Ethanol Female Folic acid Folic Acid - administration & dosage Food Genetic factors Genetic Predisposition to Disease Genetic testing Health care Humans Inventories Leukocytes Leukocytes - metabolism Metabolism Methionine Methylenetetrahydrofolate reductase Methylenetetrahydrofolate Reductase (NADPH2) - genetics Methylenetetrahydrofolate Reductase (NADPH2) - metabolism Original Peripheral blood Polymorphism, Single Nucleotide Questionnaires Regression analysis Single-nucleotide polymorphism Standard deviation Statistical analysis Studies Vitamin B Vitamin B 12 - administration & dosage Vitamin B 6 - administration & dosage Vitamin B12 Vitamin B6 Vitamins Vitamins - administration & dosage |
| title | Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA |
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