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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals</title><author><name sortKey="Vollset, Stein Emil" sort="Vollset, Stein Emil" uniqKey="Vollset S" first="Stein Emil" last="Vollset">Stein Emil Vollset</name><affiliation><nlm:aff id="A1">Norwegian Institute of Public Health and Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lewington, Sarah" sort="Lewington, Sarah" uniqKey="Lewington S" first="Sarah" last="Lewington">Sarah Lewington</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Ebbing, Marta" sort="Ebbing, Marta" uniqKey="Ebbing M" first="Marta" last="Ebbing">Marta Ebbing</name><affiliation><nlm:aff id="A3">Department of Heart Disease, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Halsey, Jim" sort="Halsey, Jim" uniqKey="Halsey J" first="Jim" last="Halsey">Jim Halsey</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lonn, Eva" sort="Lonn, Eva" uniqKey="Lonn E" first="Eva" last="Lonn">Eva Lonn</name><affiliation><nlm:aff id="A4">Population Health Research Institute and Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Armitage, Jane" sort="Armitage, Jane" uniqKey="Armitage J" first="Jane" last="Armitage">Jane Armitage</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Manson, Joann E" sort="Manson, Joann E" uniqKey="Manson J" first="Joann E" last="Manson">Joann E. Manson</name><affiliation><nlm:aff id="A5">Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Hankey, Graeme J" sort="Hankey, Graeme J" uniqKey="Hankey G" first="Graeme J" last="Hankey">Graeme J. Hankey</name><affiliation><nlm:aff id="A6">Department of Neurology, Royal Perth Hospital, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Spence, J David" sort="Spence, J David" uniqKey="Spence J" first="J David" last="Spence">J David Spence</name><affiliation><nlm:aff id="A7">Department of Neurology, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Galan, Pilar" sort="Galan, Pilar" uniqKey="Galan P" first="Pilar" last="Galan">Pilar Galan</name><affiliation><nlm:aff id="A8">Research Unit on Nutritional Epidemiology, INSERM U557, Inra, CNAM, Université Paris 13, CRNH Idf, Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="B Naa, Kaare H" sort="B Naa, Kaare H" uniqKey="B Naa K" first="Kaare H" last="B Naa">Kaare H. B Naa</name><affiliation><nlm:aff id="A9">Department of Heart Disease, University Hospital of Northern Norway, Tromsö, Norway</nlm:aff></affiliation></author><author><name sortKey="Jamison, Rex" sort="Jamison, Rex" uniqKey="Jamison R" first="Rex" last="Jamison">Rex Jamison</name><affiliation><nlm:aff id="A10">Department of Medicine, Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California, USA</nlm:aff></affiliation></author><author><name sortKey="Gaziano, J Michael" sort="Gaziano, J Michael" uniqKey="Gaziano J" first="J Michael" last="Gaziano">J Michael Gaziano</name><affiliation><nlm:aff id="A11">Massachusetts Veterans Epidemiology Research and Information Centre, VA Boston Healthcare System, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Guarino, Peter" sort="Guarino, Peter" uniqKey="Guarino P" first="Peter" last="Guarino">Peter Guarino</name><affiliation><nlm:aff id="A12">Cooperative Studies Program, Department of Veterans Affairs, Connecticut VA Healthcare System, West Haven, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Baron, John A" sort="Baron, John A" uniqKey="Baron J" first="John A" last="Baron">John A. Baron</name><affiliation><nlm:aff id="A13">Department of Medicine, University of North Carolina, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Logan, Richard Fa" sort="Logan, Richard Fa" uniqKey="Logan R" first="Richard Fa" last="Logan">Richard Fa Logan</name><affiliation><nlm:aff id="A14">Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Giovannucci, Edward L" sort="Giovannucci, Edward L" uniqKey="Giovannucci E" first="Edward L" last="Giovannucci">Edward L. Giovannucci</name><affiliation><nlm:aff id="A15">Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Den Heijer, Martin" sort="Den Heijer, Martin" uniqKey="Den Heijer M" first="Martin" last="Den Heijer">Martin Den Heijer</name><affiliation><nlm:aff id="A16">Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ueland, Per M" sort="Ueland, Per M" uniqKey="Ueland P" first="Per M" last="Ueland">Per M. Ueland</name><affiliation><nlm:aff id="A17">Institute of Medicine, University of Bergen, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Bennett, Derrick" sort="Bennett, Derrick" uniqKey="Bennett D" first="Derrick" last="Bennett">Derrick Bennett</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Collins, Rory" sort="Collins, Rory" uniqKey="Collins R" first="Rory" last="Collins">Rory Collins</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Peto, Richard" sort="Peto, Richard" uniqKey="Peto R" first="Richard" last="Peto">Richard Peto</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23352552</idno><idno type="pmc">3836669</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836669</idno><idno type="RBID">PMC:3836669</idno><idno type="doi">10.1016/S0140-6736(12)62001-7</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001F33</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001F33</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals</title><author><name sortKey="Vollset, Stein Emil" sort="Vollset, Stein Emil" uniqKey="Vollset S" first="Stein Emil" last="Vollset">Stein Emil Vollset</name><affiliation><nlm:aff id="A1">Norwegian Institute of Public Health and Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lewington, Sarah" sort="Lewington, Sarah" uniqKey="Lewington S" first="Sarah" last="Lewington">Sarah Lewington</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Ebbing, Marta" sort="Ebbing, Marta" uniqKey="Ebbing M" first="Marta" last="Ebbing">Marta Ebbing</name><affiliation><nlm:aff id="A3">Department of Heart Disease, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Halsey, Jim" sort="Halsey, Jim" uniqKey="Halsey J" first="Jim" last="Halsey">Jim Halsey</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lonn, Eva" sort="Lonn, Eva" uniqKey="Lonn E" first="Eva" last="Lonn">Eva Lonn</name><affiliation><nlm:aff id="A4">Population Health Research Institute and Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Armitage, Jane" sort="Armitage, Jane" uniqKey="Armitage J" first="Jane" last="Armitage">Jane Armitage</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Manson, Joann E" sort="Manson, Joann E" uniqKey="Manson J" first="Joann E" last="Manson">Joann E. Manson</name><affiliation><nlm:aff id="A5">Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Hankey, Graeme J" sort="Hankey, Graeme J" uniqKey="Hankey G" first="Graeme J" last="Hankey">Graeme J. Hankey</name><affiliation><nlm:aff id="A6">Department of Neurology, Royal Perth Hospital, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Spence, J David" sort="Spence, J David" uniqKey="Spence J" first="J David" last="Spence">J David Spence</name><affiliation><nlm:aff id="A7">Department of Neurology, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Galan, Pilar" sort="Galan, Pilar" uniqKey="Galan P" first="Pilar" last="Galan">Pilar Galan</name><affiliation><nlm:aff id="A8">Research Unit on Nutritional Epidemiology, INSERM U557, Inra, CNAM, Université Paris 13, CRNH Idf, Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="B Naa, Kaare H" sort="B Naa, Kaare H" uniqKey="B Naa K" first="Kaare H" last="B Naa">Kaare H. B Naa</name><affiliation><nlm:aff id="A9">Department of Heart Disease, University Hospital of Northern Norway, Tromsö, Norway</nlm:aff></affiliation></author><author><name sortKey="Jamison, Rex" sort="Jamison, Rex" uniqKey="Jamison R" first="Rex" last="Jamison">Rex Jamison</name><affiliation><nlm:aff id="A10">Department of Medicine, Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California, USA</nlm:aff></affiliation></author><author><name sortKey="Gaziano, J Michael" sort="Gaziano, J Michael" uniqKey="Gaziano J" first="J Michael" last="Gaziano">J Michael Gaziano</name><affiliation><nlm:aff id="A11">Massachusetts Veterans Epidemiology Research and Information Centre, VA Boston Healthcare System, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Guarino, Peter" sort="Guarino, Peter" uniqKey="Guarino P" first="Peter" last="Guarino">Peter Guarino</name><affiliation><nlm:aff id="A12">Cooperative Studies Program, Department of Veterans Affairs, Connecticut VA Healthcare System, West Haven, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Baron, John A" sort="Baron, John A" uniqKey="Baron J" first="John A" last="Baron">John A. Baron</name><affiliation><nlm:aff id="A13">Department of Medicine, University of North Carolina, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Logan, Richard Fa" sort="Logan, Richard Fa" uniqKey="Logan R" first="Richard Fa" last="Logan">Richard Fa Logan</name><affiliation><nlm:aff id="A14">Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Giovannucci, Edward L" sort="Giovannucci, Edward L" uniqKey="Giovannucci E" first="Edward L" last="Giovannucci">Edward L. Giovannucci</name><affiliation><nlm:aff id="A15">Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Den Heijer, Martin" sort="Den Heijer, Martin" uniqKey="Den Heijer M" first="Martin" last="Den Heijer">Martin Den Heijer</name><affiliation><nlm:aff id="A16">Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ueland, Per M" sort="Ueland, Per M" uniqKey="Ueland P" first="Per M" last="Ueland">Per M. Ueland</name><affiliation><nlm:aff id="A17">Institute of Medicine, University of Bergen, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Bennett, Derrick" sort="Bennett, Derrick" uniqKey="Bennett D" first="Derrick" last="Bennett">Derrick Bennett</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Collins, Rory" sort="Collins, Rory" uniqKey="Collins R" first="Rory" last="Collins">Rory Collins</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Peto, Richard" sort="Peto, Richard" uniqKey="Peto R" first="Richard" last="Peto">Richard Peto</name><affiliation><nlm:aff id="A2">Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</nlm:aff></affiliation></author></analytic><series><title level="j">Lancet</title><idno type="ISSN">0140-6736</idno><idno type="eISSN">1474-547X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec id="S1"><title>Background</title><p id="P2">Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials.</p></sec><sec id="S2"><title>Methods</title><p id="P3">Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period.</p></sec><sec id="S3"><title>Findings</title><p id="P4">During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site.</p></sec><sec id="S4"><title>Interpretation</title><p id="P5">Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment.</p></sec><sec id="S5"><title>Funding</title><p id="P6">British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2985213R</journal-id><journal-id journal-id-type="pubmed-jr-id">5470</journal-id><journal-id journal-id-type="nlm-ta">Lancet</journal-id><journal-id journal-id-type="iso-abbrev">Lancet</journal-id><journal-title-group><journal-title>Lancet</journal-title></journal-title-group><issn pub-type="ppub">0140-6736</issn><issn pub-type="epub">1474-547X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23352552</article-id><article-id pub-id-type="pmc">3836669</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(12)62001-7</article-id><article-id pub-id-type="manuscript">NIHMS525893</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vollset</surname><given-names>Stein Emil</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Robert</given-names></name><degrees>FRCP</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lewington</surname><given-names>Sarah</given-names></name><degrees>DPhil</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ebbing</surname><given-names>Marta</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Halsey</surname><given-names>Jim</given-names></name><degrees>BSc</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lonn</surname><given-names>Eva</given-names></name><degrees>FRCPC</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Armitage</surname><given-names>Jane</given-names></name><degrees>FRCP</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Manson</surname><given-names>JoAnn E</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Hankey</surname><given-names>Graeme J</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Spence</surname><given-names>J David</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Galan</surname><given-names>Pilar</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Bønaa</surname><given-names>Kaare H</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Jamison</surname><given-names>Rex</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Gaziano</surname><given-names>J Michael</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Guarino</surname><given-names>Peter</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Baron</surname><given-names>John A</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Logan</surname><given-names>Richard FA</given-names></name><degrees>FRCP</degrees><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Giovannucci</surname><given-names>Edward L</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>den Heijer</surname><given-names>Martin</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Ueland</surname><given-names>Per M</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Bennett</surname><given-names>Derrick</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Collins</surname><given-names>Rory</given-names></name><degrees>FMedSci</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Peto</surname><given-names>Richard</given-names></name><degrees>FRS</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><on-behalf-of>for the B-Vitamin Treatment Trialists’ Collaboration (collaborators listed at end of report)</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Norwegian Institute of Public Health and Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway</aff><aff id="A2"><label>2</label>Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Oxford, UK</aff><aff id="A3"><label>3</label>Department of Heart Disease, Haukeland University Hospital, Bergen, Norway</aff><aff id="A4"><label>4</label>Population Health Research Institute and Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada</aff><aff id="A5"><label>5</label>Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, USA</aff><aff id="A6"><label>6</label>Department of Neurology, Royal Perth Hospital, Perth, Australia</aff><aff id="A7"><label>7</label>Department of Neurology, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada</aff><aff id="A8"><label>8</label>Research Unit on Nutritional Epidemiology, INSERM U557, Inra, CNAM, Université Paris 13, CRNH Idf, Bobigny, France</aff><aff id="A9"><label>9</label>Department of Heart Disease, University Hospital of Northern Norway, Tromsö, Norway</aff><aff id="A10"><label>10</label>Department of Medicine, Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California, USA</aff><aff id="A11"><label>11</label>Massachusetts Veterans Epidemiology Research and Information Centre, VA Boston Healthcare System, Boston, Massachusetts, USA</aff><aff id="A12"><label>12</label>Cooperative Studies Program, Department of Veterans Affairs, Connecticut VA Healthcare System, West Haven, Connecticut, USA</aff><aff id="A13"><label>13</label>Department of Medicine, University of North Carolina, Chapel Hill, NC, USA</aff><aff id="A14"><label>14</label>Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK</aff><aff id="A15"><label>15</label>Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</aff><aff id="A16"><label>16</label>Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands</aff><aff id="A17"><label>17</label>Institute of Medicine, University of Bergen, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway</aff><author-notes><corresp id="FN1">Correspondence to Dr Robert Clarke, CTSU, Richard Doll Building, University of Oxford Old Road Campus, Oxford OX3 7LF, UK: <email>robert.clarke@ctsu.ox.ac.uk</email> or to Prof Stein Emil Vollset, Norwegian Institute of Public Health and University of Bergen, Kalfarveien 31, Bergen 5020, Norway: <email>vollset@uib.no</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>4</day><month>11</month><year>2013</year></pub-date><pub-date pub-type="ppub"><day>23</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>21</day><month>11</month><year>2013</year></pub-date><volume>381</volume><issue>9871</issue><elocation-id>10.1016/S0140-6736(12)62001-7</elocation-id><abstract><title>Summary</title><sec id="S1"><title>Background</title><p id="P2">Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials.</p></sec><sec id="S2"><title>Methods</title><p id="P3">Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period.</p></sec><sec id="S3"><title>Findings</title><p id="P4">During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site.</p></sec><sec id="S4"><title>Interpretation</title><p id="P5">Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment.</p></sec><sec id="S5"><title>Funding</title><p id="P6">British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.</p></sec></abstract><funding-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>R01 CA059005 || CA</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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