Folate, vitamin B6, vitamin B12, and methionine are involved in DNA synthesis and methylation and thus may modulate pancreatic cancer risk. We investigated these associations in a population-based case-control study conducted in 1994–1998.
Cases (n = 150) were identified from all hospitals in the metropolitan areas of the Twin Cities and the Mayo Clinic, Minnesota. Controls (n = 459) were selected randomly from the general population and were frequency matched to cases by age, sex, and race. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for risk of pancreatic cancer in relation to intake of nutrients considered.
Dietary intake of folate was associated with a reduced pancreatic cancer risk [OR (95% CI) for quartile (Q) 4 vs. Q1: 0.31 (0.12–0.78)]. A composite score (range from 2 to 8), reflecting combined dietary intake of folate and vitamin B6, was also inversely associated with pancreatic cancer risk [OR (95% CI) for Q4 vs. Q1: 0.24 (0.08–0.70)]. Null associations were found for intake of vitamin B12 and methionine.
Dietary folate intake was associated with a reduced pancreatic cancer risk, and this association became stronger when dietary intake of folate and vitamin B6 was combined in analysis.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis
Nutrition Journal Open Access 04 October 2020
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363:1049–57.
Shin EJ, Canto MI. Pancreatic cancer screening. Gastroenterol Clin North Am. 2012;41:143.
O’leary B, Du J, Heer C, Van Beek H, Sptiz DR, Cullen JJ. Inhibition of peroxide removal enhances pharmacological ascorbate and ionizing radiation-induced cytotoxicity of pancreatic ductal adenocarcinoma. Free Radic Biol Med. 2017;112:97.
American Cancer Society. Cancer Facts & Figures 2017. Atlanta, GA: American Cancer Society; 2017.
Lucas AL, Malvezzi M, Carioli G, Negri E, La Vecchia C, Boffetta P, et al. Global trends in pancreatic cancer mortality from 1980 through 2013 and predictions for 2017. Clin Gastroenterol Hepatol. 2016;14:1452–62. e4.
Zhang J, Dhakal IB, Gross MD, Lang NP, Kadlubar FF, Harnack LJ, et al. Physical activity, diet, and pancreatic cancer: a population-based, case-control study in Minnesota. Nutr Cancer. 2009;61:457–65.
Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Prospective study of diet and pancreatic cancer in male smokers. Am J Epidemiol. 2002;155:783–92.
Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, et al. Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 2007;67:5553–60.
Stolzenberg-Solomon RZ, Albanes D, Nieto FJ, Hartman TJ, Tangrea JA, Rautalahti M, et al. Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst. 1999;91:535–41.
Mocellin S, Briarava M, Pilati P. Vitamin B6 and cancer risk: a field synopsis and meta-analysis. J Natl Cancer Inst. 2017;109:1–9.
Bailey LB, Gregory JF. Folate metabolism and requirements. J Nutr. 1999;129:779–82.
Tan AC, Jimeno A, Lin SH, Wheelhouse J, Chan F, Solomon A, et al. Characterizing DNA methylation patterns in pancreatic cancer genome. Mol Oncol. 2009;3:425–38.
Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, et al. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res. 2003;63:3735–42.
Gong Z, Holly EA, Bracci PM. Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case–control study. Cancer Causes Control. 2009;20:1317–25.
Larsson SC, Håkansson N, Giovannucci E, Wolk A. Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst. 2006;98:407–13.
Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol. 2001;153:680–7.
Bao Y, Michaud DS, Spiegelman D, Albanes D, Anderson KE, Bernstein L, et al. Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies. J Natl Cancer Inst. 2011;103:1840–50.
Huang JY, Butler LM, Wang R, Jin A, Koh WP, Yuan JM. Dietary intake of one-carbon metabolism-related nutrients and pancreatic cancer risk: The Singapore Chinese Health Study. Cancer Epidemiol Biomark Prev. 2016;25:417–24.
Anderson KE, Sinha R, Kulldorff M, Gross M, Lang NP, Barber C, et al. Meat intake and cooking techniques: associations with pancreatic cancer. Mutat Res. 2002;506:225–31.
Gross M, Kruisselbrink T, Anderson K, Lang N, McGovern P, Delongchamp R, et al. Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population. Cancer Epidemiol Biomark Prev. 1999;8:683–92.
Willett W, Reynolds R, Cottrell-Hoehner S, Sampson L, Browne M. Validation of a semi-quantitative food frequency questionnaire: comparison with a 1-year diet record. J Am Diet Assoc. 1987;87:43–7.
Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ, Litin LB, et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc. 1993;93:790–6.
Fratoni V, Brandi ML. B vitamins, homocysteine and bone health. Nutrients. 2015;7:2176–92.
Skinner HG, Michaud DS, Giovannucci EL, Rimm EB, Stampfer MJ, Willett WC, et al. A prospective study of folate intake and the risk of pancreatic cancer in men and women. Am J Epidemiol. 2004;160:248–58.
Marques-Vidal P, Pecoud A, Hayoz D, Paccaud F, Mooser V, Waeber G, et al. Prevalence and characteristics of vitamin or dietary supplement users in Lausanne, Switzerland: the CoLaus study. Eur J Clin Nutr. 2009;63:273.
Klipstein-Grobusch K, Kroke A, Voss S, Boeing H. [Influence of lifestyle on the use of supplements in the Brandenburg nutrition and cancer study]. Z Ernahr. 1998;37:38–46.
Harrison RA, Holt D, Pattison DJ, Elton PJ. Are those in need taking dietary supplements? A survey of 21 923 adults. Br J Nutr. 2004;91:617–23.
Chuang S-C, Stolzenberg-Solomon R, Ueland PM, Vollset SE, Midttun Ø, Olsen A, et al. A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer. 2011;47:1808–16.
Larsson SC, Giovannucci E, Wolk A. Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men. Gastroenterology. 2007;132:113–8.
Balaghi M, Wagner C. Methyl group metabolism in the pancreas of folate-deficient rats. J Nutr. 1992;122:1391–6.
Kim YI, Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer?. Cancer Epidemiol Biomark Prev. 2004;13:511–9.
Chen RZ, Pettersson U, Beard C, Jackson-Grusby L, Jaenisch R. DNA hypomethylation leads to elevated mutation rates. Nature. 1998;395:89–93.
Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natil Acad Sci USA. 1997;94:3290–5.
Fenech M,Dreosti I,Rinaldi J, Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis. 1997;18:1329–36.
Baghurst PA, McMichael AJ, Slavotinek AH, Baghurst KI, Boyle P, Walker AM. A case-control study of diet and cancer of the pancreas. Am J Epidemiol. 1991;134:167–79.
Howe G, Jain M, Miller A. Dietary factors and risk of pancreatic cancer: results of a Canadian population‐based case‐control study. Int J Cancer. 1990;45:604–8.
De Mesquita HB, Maisonneuve P, Runia S, Moerman C. Intake of foods and nutrients and cancer of the exocrine pancreas: a population‐based case‐control study in the Netherlands. Int J Cancer. 1991;48:540–9.
Howe G, Ghadirian P, de Mesquita H, Zatonski W, Baghurst P, Miller A, et al. A collaborative case‐control study of nutrient intake and pancreatic cancer within the search programme. Int J Cancer. 1992;51:365–72.
Ghadirian P, Simard A, Baillargeon J, Maisonneuve P, Boyle P. Nutritional factors and pancreatic cancer in the francophone community in Montreal, Canada. Int J Cancer. 1991;47:1–6.
Nkondjock A, Krewski D, Johnson KC, Ghadirian P. Dietary patterns and risk of pancreatic cancer. Int J Cancer. 2005;114:817–23.
Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;122:51–65.
Yuan C, Spiegelman D, Rimm EB, Rosner BA, Stampfer MJ, Barnett JB, et al. Relative validity of nutrient intakes assessed by questionnaire, 24-hour recalls, and diet records compared with urinary recovery and plasma concentration biomarkers: findings for women. Am J Epidemiol. 2017;187:1051–63.
Larsson SC, Orsini N, Wolk A. Body mass index and pancreatic cancer risk: a meta‐analysis of prospective studies. Int J Cancer. 2007;120:1993–8.
Research reported in this publication was supported by the National Institutes of Health (R01CA58697 to Dr. Kristin Anderson and T32CA117865 to Dr. Victoria Champion). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Marley, A.R., Fan, H., Hoyt, M.L. et al. Intake of methyl-related nutrients and risk of pancreatic cancer in a population-based case-control study in Minnesota. Eur J Clin Nutr 72, 1128–1135 (2018). https://doi.org/10.1038/s41430-018-0228-5
This article is cited by
Folate Intake and Risk of Pancreatic Cancer: A Systematic Review and Updated Meta-Analysis of Epidemiological Studies
Digestive Diseases and Sciences (2021)
Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis
Nutrition Journal (2020)