Skip to main content
SpringerLink
Log in

Serum B6 vitamers (pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid) and pancreatic cancer risk: two nested case–control studies in Asian populations

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Background

Vitamin B6 is an important enzymatic cofactor in pathways relevant for the development of pancreatic cancer. In order to evaluate vitamin B6 as a preventive factor for pancreatic cancer, a biomarker approach is needed to overcome the limitations inherent in self-reported dietary information.

Methods

To determine whether levels of serum B6 vitamers, including pyridoxal 5′-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), and the PA/(PLP + PL) ratio (PAr), were associated with risk of pancreatic cancer, two nested case–control studies of 187 incident pancreatic cancer cases and 258 individually matched controls were conducted within two prospective cohorts of 81,501 participants in Shanghai, China, and Singapore. PLP, PL, and PA were quantified in pre-diagnostic serum samples. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for potential confounders.

Results

The median (5th–95th percentiles) concentrations of serum PLP among control subjects of the Shanghai and Singapore cohorts were 25.7 (10.0–91.7) nmol/L and 58.1 (20.8–563.0) nmol/L, respectively. In pooled analyses, high serum PLP was associated with a reduced risk of pancreatic cancer (P for trend = 0.048); the adjusted odds ratio for the highest category of PLP (>52.4 nmol/L) was 0.46 (95% CI 0.23, 0.92) compared to vitamin B6 deficiency (<20 nmol/L). No associations were found for serum PL, PA, or PAr with pancreatic cancer risk.

Conclusions

Higher concentrations of PLP may protect against the development of pancreatic cancer. The protective effect may be more apparent in populations with low concentrations of circulating vitamin B6.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386

    Article  CAS  PubMed  Google Scholar 

  2. Lynch SM, Vrieling A, Lubin JH et al (2009) Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol 170:403–413

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bracci PM (2012) Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms. Mol Carcinog 51:53–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jansen RJ, Robinson DP, Stolzenberg-Solomon RZ et al (2011) Fruit and vegetable consumption is inversely associated with having pancreatic cancer. Cancer Causes Control 22:1613–1625

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chan JM, Wang F, Holly EA (2005) Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area. Cancer Epidemiol Biomarkers Prev 14:2093–2097

    Article  PubMed  Google Scholar 

  6. US Department of Agriculture, Agricultural Research Service, Nutrient Data Laboratory (2016) USDA National Nutrient Database for Standard Reference, Release 28 (Slightly revised). Version Current: May 2016. http://www.ars.usda.gov/sp2UserFiles/Place/80400525/Data/SR/SR28/sr28_doc.pdf

  7. Huang JY, Butler LM, Wang R, Jin A, Koh WP, Yuan JM (2016) Dietary intake of one-carbon metabolism-related nutrients and pancreatic cancer risk: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 25:417–424

    Article  CAS  PubMed  Google Scholar 

  8. Larsson SC, Giovannucci E, Wolk A (2007) Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men. Gastroenterology 132:113–118

    Article  CAS  PubMed  Google Scholar 

  9. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D (2001) Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 153:680–687

    Article  CAS  PubMed  Google Scholar 

  10. Gong Z, Holly EA, Bracci PM (2009) Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control 20:1317–1325

    Article  PubMed  PubMed Central  Google Scholar 

  11. Choi SW, Friso S (2012) Vitamins B6 and cancer. Subcell Biochem 56:247–264

    Article  CAS  PubMed  Google Scholar 

  12. Albersen M, Bosma M, Luykx JJ et al (2014) Vitamin B-6 vitamers in human plasma and cerebrospinal fluid. Am J Clin Nutr 100:587–592

    Article  CAS  PubMed  Google Scholar 

  13. Ueland PM, Ulvik A, Rios-Avila L, Midttun O, Gregory JF (2015) Direct and functional biomarkers of vitamin B6 status. Annu Rev Nutr 35:33–70

    Article  CAS  PubMed  Google Scholar 

  14. Ulvik A, Midttun O, Pedersen ER, Eussen SJ, Nygard O, Ueland PM (2014) Evidence for increased catabolism of vitamin B-6 during systemic inflammation. Am J Clin Nutr 100:250–255

    Article  CAS  PubMed  Google Scholar 

  15. Greer JB, Whitcomb DC (2009) Inflammation and pancreatic cancer: an evidence-based review. Curr Opin Pharmacol 9:411–418

    Article  CAS  PubMed  Google Scholar 

  16. Schernhammer E, Wolpin B, Rifai N et al (2007) Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res 67:5553–5560

    Article  CAS  PubMed  Google Scholar 

  17. Chuang SC, Stolzenberg-Solomon R, Ueland PM et al (2011) A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer 47:1808–1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Stolzenberg-Solomon RZ, Albanes D, Nieto FJ et al (1999) Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst 91:535–541

    Article  CAS  PubMed  Google Scholar 

  19. Yuan JM, Ross RK, Wang XL, Gao YT, Henderson BE, Yu MC (1996) Morbidity and mortality in relation to cigarette smoking in Shanghai, China. A prospective male cohort study. JAMA 275:1646–1650

    Article  CAS  PubMed  Google Scholar 

  20. Yuan JM, Stram DO, Arakawa K, Lee HP, Yu MC (2003) Dietary cryptoxanthin and reduced risk of lung cancer: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 12:890–898

    CAS  PubMed  Google Scholar 

  21. Hankin JH, Stram DO, Arakawa K et al (2001) Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire. Nutr Cancer 39:187–195

    Article  CAS  PubMed  Google Scholar 

  22. Odegaard AO, Pereira MA, Koh WP, Arakawa K, Lee HP, Yu MC (2008) Coffee, tea, and incident type 2 diabetes: the Singapore Chinese Health Study. Am J Clin Nutr 88:979–985

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Odegaard AO, Koh WP, Arakawa K, Yu MC, Pereira MA (2010) Soft drink and juice consumption and risk of physician-diagnosed incident type 2 diabetes: the Singapore Chinese Health Study. Am J Epidemiol 171:701–708

    Article  PubMed  PubMed Central  Google Scholar 

  24. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB (eds) (2002) Cancer incidence in five continents vol. VIII. IARC Publication No. 155. https://www.iarc.fr/en/publications/pdfs-online/epi/sp155/CI5V8.pdf. Accessed Nov 2016

  25. Yuan JM, Koh WP, Murphy SE et al (2009) Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers. Cancer Res 69:2990–2995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Midttun O, Kvalheim G, Ueland PM (2013) High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405:2009–2017

    Article  CAS  PubMed  Google Scholar 

  27. Breslow N, Day N (1980) Statistical methods in cancer research, vol 1: the analysis of case–control studies. IARC: IARC Scientific Pub No. 32, Lyon

  28. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate OBV, and Choline (1998) Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington (DC)

  29. Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shin-Buehring Y, Rasshofer R, Endres W (1981) A new enzymatic method for pyridoxal 5′-phosphate determination. J Inherit Metab Disord 4:123–124

    Article  CAS  Google Scholar 

  31. Kannan K, Jain SK (2004) Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med 36:423–428

    Article  CAS  PubMed  Google Scholar 

  32. Kuwahara K, Nanri A, Pham NM et al (2013) Serum vitamin B6, folate, and homocysteine concentrations and oxidative DNA damage in Japanese men and women. Nutrition 29:1219–1223

    Article  CAS  PubMed  Google Scholar 

  33. Marzio A, Merigliano C, Gatti M, Verni F (2014) Sugar and chromosome stability: clastogenic effects of sugars in vitamin B6-deficient cells. PLoS Genet 10:e1004199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jiao L, Weinstein SJ, Albanes D et al (2011) Evidence that serum levels of the soluble receptor for advanced glycation end products are inversely associated with pancreatic cancer risk: a prospective study. Cancer Res 71:3582–3589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jiao L, Taylor PR, Weinstein SJ et al (2011) Advanced glycation end products, soluble receptor for advanced glycation end products, and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 20:1430–1438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Leklem JE (1990) Vitamin B-6: a status report. J Nutr 120(Suppl 11):1503–1507

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Xue-Li Wang of the Shanghai Cancer Institute for assistance with data collection and management and the staff of the Shanghai Cancer Registry for their assistance in verifying cancer diagnoses in study participants. We thank Siew-Hong Low of the National University of Singapore for supervising the fieldwork in the Singapore Chinese Health Study. We also thank The Singapore Cancer Registry for the identification of cancer and mortality outcomes via database linkages. Finally, we acknowledge the founding Principal Investigator of the Singapore Chinese Health Study, Mimi C. Yu.

Funding

The work was supported by the National Institutes of Health (NCI R01 CA144034 and UM1 CA182876).

Author information

Authors and Affiliations

  1. Division of Cancer Control and Population Science, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue – Suite 4C, Pittsburgh, PA, 15232, USA

    Joyce Y. Huang, Lesley M. Butler, Renwei Wang & Jian-Min Yuan

  2. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    Joyce Y. Huang, Lesley M. Butler & Jian-Min Yuan

  3. Bevital A/S, Bergen, Norway

    Øivind Midttun

  4. Duke-NUS Medical School, National University of Singapore, Singapore, Singapore

    Woon-Puay Koh

  5. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

    Woon-Puay Koh

  6. Department of Clinical Science, University of Bergen, Bergen, Norway

    Per M. Ueland

  7. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway

    Per M. Ueland

  8. National Registry of Diseases Office, Health Promotion Board, Singapore, Singapore

    Aizhen Jin

  9. Shanghai Jiaotong University, Shanghai, China

    Yu-Tang Gao

Authors
  1. Joyce Y. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley M. Butler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Øivind Midttun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Woon-Puay Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Per M. Ueland
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Renwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aizhen Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu-Tang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jian-Min Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesley M. Butler.

Ethics declarations

Conflict of interest

None declared.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 32 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, J.Y., Butler, L.M., Midttun, Ø. et al. Serum B6 vitamers (pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid) and pancreatic cancer risk: two nested case–control studies in Asian populations. Cancer Causes Control 27, 1447–1456 (2016). https://doi.org/10.1007/s10552-016-0822-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-016-0822-6

Keywords

Search

Navigation