Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Epidemiology

The biomarker-based validity of a food frequency questionnaire to assess the intake status of folate, pyridoxine and cobalamin among Iranian primary breast cancer patients

Abstract

Background/Objectives:

Folate, pyridoxine and cobalamin are coenzymatically essential in one-carbon methyl metabolism, and their deficiencies could explain some alterations during breast carcinogenesis. We aimed to evaluate the validity of folate, pyridoxine and cobalamin estimates from a food frequency questionnaire (FFQ) on the basis of their corresponding fasting plasma biomarkers, in breast cancer (BC) patients.

Subjects/Methods:

In a prospective, consecutive case series, 149 women with primary BC aged between 30 and 69 years as a representative sample of Iranian women with BC were recruited. The 136-item FFQ was used for the validity assay. Fasting plasma folate and cobalamin were tested by automated electrochemiluminescence. The high-pressure liquid chromatography with fluorescence detection was used to determine the plasma levels of pyridoxal-5'-phosphate (PLP) and total homocysteine (tHcy).

Results:

Area under the curve (AUC) for assessing the diagnostic accuracy of folate-related data through an FFQ was 0.74 (P<0.01) in the reference model (folate plasma level<5.9 ng/ml), with sensitivity and specificity of 68% and 63%, respectively. The positive and negative predictive values (PPV and NPV) were 96.9% and 96.8%, respectively. The AUC for cobalamin intake in the reference model (plasma cobalamin<260 pmol/l) was 0.64 (P<0.01), with 60% sensitivity and 61% specificity. Although tHcy10.0 μmol/l was used as reference indicator, the folate intake (AUC=0.71, P<0.01) and cobalamin intake status (AUC=0.67, P<0.05) were also determined appropriately by FFQ.

Conclusions:

Dietary folate and cobalamin estimates from FFQ were significantly correlated with their fasting plasma concentrations. Our data supported the validity of new FFQ to rank individuals by dietary intake status of folate and cobalamin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Chou YC, Wu MH, Yu JC, Lee MS, Yang T, Shih HL et al. Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case–control study in Taiwan. Carcinogenesis 2006; 27: 2295–2300.

    Article  CAS  Google Scholar 

  2. Larsson SC, Giovannucci E, Wolk A . Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 2007; 99: 64–76.

    Article  CAS  Google Scholar 

  3. Johnson IT, Belshaw NJ . Environment, diet and CpG island methylation: epigenetic signals in gastrointestinal neoplasia. Food Chem Toxicol 2008; 46: 1346–1359.

    Article  CAS  Google Scholar 

  4. Verkleij-Hagoort AC, de Vries JH, Stegers MP, Lindemans J, Ursem NT, Steegers-Theunissen RP . Validation of the assessment of folate and vitamin B12 intake in women of reproductive age: the method of triads. Eur J Clin Nutr 2007; 61: 610–615.

    Article  CAS  Google Scholar 

  5. Choi SW . Vitamin B12 deficiency: a new risk factor for breast cancer? Nutr Rev 1999; 57: 250–253.

    CAS  PubMed  Google Scholar 

  6. Stempak JM, Sohn KJ, Chiang EP, Shane B, Kim YI . Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 2005; 26: 981–990.

    Article  CAS  Google Scholar 

  7. Pirouzpanah S, Taleban FA, Abadi AR, Atri M, Mehdipour P . The association of plasma folate, vitamin B12 and homocysteine levels on hypermethylation status of RARβ2 gene in primary breast carcinoma. Iran J Epidemiol 2009; 5: 17–19. (Persian).

    Google Scholar 

  8. Lin J, Lee IM, Cook NR, Selhub J, Manson JAE, Buring JE et al. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr 2008; 87: 734–743.

    Article  CAS  Google Scholar 

  9. Kim YI . Does a high folate intake increase the risk of breast cancer? Nutr Rev 2006; 64: 468–475.

    Article  Google Scholar 

  10. Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K et al. Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 2007; 61: 1435–1441.

    Article  CAS  Google Scholar 

  11. Jackson M, Walker S, Younger N, Bennett F . Use of a food frequency questionnaire to assess diets of Jamaican adults: validation and correlation with biomarkers. Nutr J 2011; 10: 28.

    Article  Google Scholar 

  12. Flood VM, Smith WT, Webb KL, Mitchell P . Issues in assessing the validity of nutrient data obtained from a food-frequency questionnaire: folate and vitamin B12 examples. Public Health Nutr 2004; 7: 751–756.

    Article  Google Scholar 

  13. Carlsen MH, Karlsen A, Lillegaard ITL, Gran JM, Drevon CA, Blomhoff R et al. Relative validity of fruit and vegetable intake estimated from an FFQ, using carotenoid and flavonoid biomarkers and the method of triads. Brit J Nutr 2011; 105: 1530–1538.

    Article  CAS  Google Scholar 

  14. Willett W . Issues in analysis and presentation of dietary data. In Nutritional Epidemiology 2nd edn, Oxford University Press: New York. pp 321–346, 1998.

    Chapter  Google Scholar 

  15. Owens JE, Holstege DM, Clifford AJ . Comparison of two dietary folate intake instruments and their validation by RBC folate. J Agric Food Chem 2007; 55: 3737–3740.

    Article  CAS  Google Scholar 

  16. Signorello LB, Buchowski MS, Cai Q, Munro HM, Hargreaves MK, Blot WJ . Biochemical validation of food frequency questionnaire-estimated carotenoid, alpha-tocopherol and folate intakes among African Americans and non-Hispanic Whites in the Southern Community Cohort Study. Am J Epidemiol 2010; 171: 488–497.

    Article  Google Scholar 

  17. Brunner E, Stallone D, Juneja M, Bingham S, Marmot M . Dietary assessment in Whitehall II: comparison of 7 d diet diary and food-frequency questionnaire and validity against biomarkers. Br J Nutr 2001; 86: 405–414.

    Article  CAS  Google Scholar 

  18. Cheng CH, Tsai TP, Chen WS, Huang YC . Serum folate is a reliable indicator of hyperhomocysteinemia and borderline hyperhomocysteinemia in young adults. Nutr Res 2009; 29: 743–749.

    Article  CAS  Google Scholar 

  19. Baric IC, Satalic Z, Keser I, Cecic I, Sucic M . Validation of the folate food frequency questionnaire with serum and erythrocyte folate and plasma homocysteine. Int J Food Sci Nutr 2009; 60: 10–18.

    Article  CAS  Google Scholar 

  20. Jaffe JP, Schilling RF . Erythrocyte folate levels: a clinical study. Am J Hematol 1991; 36: 116–121.

    Article  CAS  Google Scholar 

  21. Melnyk S, Pogribna M, Pogribny IP, Yi P, James SJ . Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: alterations with plasma homocysteine and pyridoxal 5'-phosphate concentrations. Clin Chem 2000; 46: 265–272.

    CAS  PubMed  Google Scholar 

  22. Yoshino K, Nishide M, Inagawa M, Yokota K, Moriyama Y, Ikeda A et al. Validity of brief food frequency questionnaire for estimation of dietary intakes of folate, vitamins B6 and B12, and their associations with plasma homocysteine concentrations. Int J Food Sci Nutr 2011; 61: 61–67.

    Article  Google Scholar 

  23. Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH et al. Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr 2004; 58: 481–487.

    Article  CAS  Google Scholar 

  24. Da Silva R, Bach-Faig A, Raidio Quintana B, Buckland G, Vaz de Almeida MD, Serra-Majem L . Worldwide variation of adherence to the Mediterranean diet, in 1961–1965 and 2000–2003. Public Health Nutr 2009; 12: 1676–1684.

    Article  Google Scholar 

  25. Fayet F, Flood V, Petocz P, Samman S . Relative and biomarker-based validity of a food frequency questionnaire that measures the intakes of vitamin B(12), folate, iron, and zinc in young women. Nutr Res 2011; 31: 14–20.

    Article  CAS  Google Scholar 

  26. Pirouzpanah S, Taleban FA, Atri M, Abadi AR, Mehdipour P . The effect of modifiable potentials on hypermethylation status of retinoic acid receptor-beta2 and estrogen receptor-alpha genes in primary breast cancer. Cancer Cause Control 2010; 21: 2101–2111.

    Article  Google Scholar 

  27. Goldberg GR, Black AE, Jebb SA, Cole TJ, Murgatroyd PR, Coward WA et al. Critical evaluation of energy intake data using fundamental principles of energy physiology: 1. Derivation of cut-off limits to identify under-recording. Eur J Clin Nutr 1991; 45: 569–581.

    CAS  PubMed  Google Scholar 

  28. Black AE . Physical activity levels from a meta analysis of doubly labeled water studies for validating energy intake as measured by dietary assessment. Nutr Rev 1996; 54: 170–174.

    Article  CAS  Google Scholar 

  29. Schofield WN . Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr 1985; 39: 5–41.

    PubMed  Google Scholar 

  30. Pirouzpanah S, Taleban FA, Sabour S, Mehdipour P, Atri M, Farrin N et al. Validation of food frequency questionnaire to assess folate intake status in breast cancer patients (In Faris). Razi J Med Sci 2012; 18: 31–41.

    Google Scholar 

  31. Ghaffarpour M, Housyar-Rad A, Kianfar T . The Manual for Household Measures, Cooking Yields Factors and Edible Portion of Food. Keshavarzi Press: Tehran, 1999.

    Google Scholar 

  32. Gallagher ML . Intake: the nutrients and their metabolism. In Mahan LK, Escott-Stump S, Raymond JL, (eds) Krause's food and the nutrition care process 13 edn, Elsevier: Missouri, 2012.

    Google Scholar 

  33. Gebhardt SE, Lemar LE, Pehrsson PR, Exler J, Haytowitz DB, Patterson KK et alUSDA National Nutrient Database for Standard Reference, vol. Release 22, 2009.

  34. Willett WC . Invited commentary: a further look at dietary questionnaire validation. Am J Epidemiol 2001; 154: 1100–1102.

    Article  CAS  Google Scholar 

  35. Ihara H, Watanabe T, Aoki Y, Nagamura Y, Totani M, Hashizume N . Dietary folate intake and serum folate status in Japanese women of childbearing age. J Anal Bio-Sci 2009; 32: 181–185.

    CAS  Google Scholar 

  36. Pellis L, Dommels Y, Venema D, Polanen A, Lips E, Baykus H et al. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Brit J Nutr 2008; 99: 703–708.

    Article  CAS  Google Scholar 

  37. Lui A, Lumeng L, Aronoff GR, Ting-Kai LI . Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans. J Lab Clin Med 1985; 106: 491–497.

    CAS  PubMed  Google Scholar 

  38. Van Asselt DZ, de Groot LC, van Staveren WA, Blom HJ, Wevers RA, Biemond I et al. Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. Am J Clin Nutr 1998; 68: 328–334.

    Article  CAS  Google Scholar 

  39. Jekel JF, Katz DL, Elmore JG . Epidemiology, Biostatistics and Preventive Medicine 2nd edn., W.B. Saunders company: Philadelphia, 2001.

    Google Scholar 

  40. Swets JA . Measuring the accuracy of diagnostic systems. Science 1998; 240: 1285–1293.

    Article  Google Scholar 

  41. Iso H, Moriyama Y, Yoshino K, Sasaki S, Ishihara J, Tsugane S . Validity of the self-administered food frequency questionnaire used in the 5-year follow-up survey for the JPHC Study to assess folate, vitamin be and B12 intake: Comparison with dietary records and blood level. J Expo Anal Environ Epidemiol 2003; 13: S98–S101.

    Google Scholar 

  42. Willett WC, Lenart E . Reproducibility and validity of food frequency questionnaire. In: Willett WC, (ed) Nutritional Epidemiology 2nd edn, Oxford University Press: New York. pp 101–147, 1998.

    Chapter  Google Scholar 

  43. Yen J, Zoumas-Morse C, Pakiz B, Rock CL . Folate intake assessment: validation of a new approach. J Am Diet Assoc 2003; 103: 991–1000.

    Article  Google Scholar 

  44. Kipnis V, Subar AF, Midthune D, Freedman LS, Ballard-Barbash R, Troiano RP et al. Structure of dietary measurement error: results of the OPEN biomarker study. Am J Epidemiol 2003; 158: 14–21.

    Article  Google Scholar 

  45. Johansson I, Van Guelpen B, Hultdin J, Johansson M, Hallmans G, Stattin P . Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification. Eur J Clin Nutr 2010; 64: 905–913.

    Article  CAS  Google Scholar 

  46. Mirmiran P, Hosseini-Esfahani F, Mehrabi Y, Hedayati M, Azizi F . Reliability and relative validity of an FFQ for nutrients in the Tehran Lipid and Glucose Study. Public Health Nutr 2009; 13: 654–662.

    Article  Google Scholar 

  47. Nelson M . The Validity of Dietary Questionnaires. In: Margetts B, Nelson M, (eds) Design Concepts in Nutritional Epidemiology. Oxford University Press: New York, USA, 1991.

    Google Scholar 

  48. Liu A, Lumeng L, Aronoff G, Li TK . Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans. J Lab Clin Med 1985; 106: 491–497.

    Google Scholar 

  49. Bates CJ, Thurnham DI, Bingham SA, Margetts BM, Nelson M . Biochemical markers of nutrient intake. In: Margetts BM, Nelson M, (eds) Design concepts in nutritional epidemiology. Oxford University Press: New York, US, 1995.

    Google Scholar 

  50. Morris MS, Sakakeeny L, Jacques PF, Picciano MF, Selhub J . Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr 2010; 140: 103–110.

    Article  CAS  Google Scholar 

  51. Daures JP, Gerber M, Scali J, Astre C, Bonifacj C, Kaaks R . Validation of a food-frequency questionnaire using multiple-day records and biochemical markers: application of the triads method. J Epidemiol Biostat 2000; 5: 109–115.

    CAS  PubMed  Google Scholar 

  52. De Bree A, Verschuren WMM, Bjrke-Monsen AL, van der Put NMJ, Heil SG, Trijbels FJM et al. Effect of the methylenetetrahydrofolate reductase 677C→T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr 2003; 77: 687–693.

    Article  CAS  Google Scholar 

  53. Van Engeland M, Weijenberg MP, Roemen GMJM, Brink M, de Bruïne AP, Goldbohm RA et al. Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands Cohort Study on diet and cancer. Cancer Res 2003; 63: 3133–3137.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all participating patients and our valued colleagues in the Day General Hospital. We are also grateful to research affair of National Nutrition & Food Technology Research Institute, Shaheed Beheshti University of Medical Sciences, Iran, for providing financial support to conduct this study. The financial support for conception, design, data analysis and manuscript drafting comes from Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran. The author’s responsibilities were as follows: SP and FAT, MA and AH: study design; SP, MA and PM: data ollection; SP, AH and SS: laboratory and data analysis; and SP, and SS: writing of manuscript. The authors are grateful to Dr. Mohammad-Amin Tabatabaifar for his valuable reading of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Pirouzpanah.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pirouzpanah, S., Taleban, FA., Mehdipour, P. et al. The biomarker-based validity of a food frequency questionnaire to assess the intake status of folate, pyridoxine and cobalamin among Iranian primary breast cancer patients. Eur J Clin Nutr 68, 316–323 (2014). https://doi.org/10.1038/ejcn.2013.209

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2013.209

Keywords

This article is cited by

Search

Quick links