{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:22:30Z","timestamp":1763036550663},"reference-count":20,"publisher":"American Association for Cancer Research (AACR)","issue":"11","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Vitamin B12, holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A&amp;gt;G and SHMT1 1420C&amp;gt;T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with prostate-specific antigen (PSA) velocity (PSAV) as a proxy measure of prostate cancer progression in men with localized prostate cancer.<\/jats:p>\n               <jats:p>Methods: We measured plasma folate, B12, holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine at diagnosis in 424 men (ages 45-70 years) with localized prostate cancer in a U.K.-wide population-based cohort. Thirteen folate-pathway single-nucleotide polymorphisms were genotyped for 311 of these men. Postdiagnosis PSAV (continuous measure and with a threshold set a priori at 2 ng\/mL\/y) was estimated from repeat PSA measurements.<\/jats:p>\n               <jats:p>Results: Median follow-up time was 2.5 (range, 0.8-5.6) years. Vitamin B12, holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine were not associated with postdiagnosis PSAV. Folate was associated with an increased risk of PSAV &amp;gt;2 ng\/mL\/y [odds ratio (OR) per unit increase in loge concentration, 1.57; 95% confidence interval (95% CI), 0.98-2.51; P = 0.06]. MTRR 66A&amp;gt;G (rs1801394) was associated with a reduced risk (recessive model OR, 0.33; 95% CI, 0.11-0.97; P = 0.04), and SHMT1 1420C&amp;gt;T (rs1979277) with an increased risk (per-allele OR, 1.49; 95% CI, 0.93-2.37; P = 0.09) of PSAV &amp;gt;2 ng\/mL\/y.<\/jats:p>\n               <jats:p>Conclusions: We found weak evidence that higher folate levels may be associated with faster progression of localized prostate cancer.<\/jats:p>\n               <jats:p>Impact: Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication. Cancer Epidemiol Biomarkers Prev; 19(11); 2833\u20138. \u00a92010 AACR.<\/jats:p>","DOI":"10.1158\/1055-9965.epi-10-0582","type":"journal-article","created":{"date-parts":[[2010,11,8]],"date-time":"2010-11-08T14:43:11Z","timestamp":1289227391000},"page":"2833-2838","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Associations of Folate, Vitamin B12, Homocysteine, and Folate-Pathway Polymorphisms with Prostate-Specific Antigen Velocity in Men with Localized Prostate Cancer"],"prefix":"10.1158","volume":"19","author":[{"given":"Simon M.","family":"Collin","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"Refsum","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"},{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"},{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Cox","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Davis","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Marsden","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Johnston","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Athene","family":"Lane","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny L.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Neal","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freddie C.","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. David","family":"Smith","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, Bristol, United Kingdom; 3Department of Pharmacology, University of Oxford; 4Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 5Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; 6Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom; and 7Department of Oncology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081School of Social and Community Medicine and 2MRC Centre for Causal Analysis in School of Social and Community Medicine of Bristol, 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