Cancer Causes & Control

, Volume 21, Issue 7, pp 1061–1069 | Cite as

A prospective study of one-carbon metabolism biomarkers and risk of renal cell carcinoma

  • Todd M. Gibson
  • Stephanie J. Weinstein
  • Susan T. Mayne
  • Ruth M. Pfeiffer
  • Jacob Selhub
  • Philip R. Taylor
  • Jarmo Virtamo
  • Demetrius Albanes
  • Rachael Stolzenberg-Solomon
Original paper

Abstract

Objective

Previous studies have found associations between one-carbon metabolism factors and risk of several cancers, but little is known regarding renal cell carcinoma (RCC). We conducted a nested case–control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a prospective study of Finnish male smokers aged 50–69 at baseline.

Methods

Prediagnostic folate, vitamin B6, vitamin B12, cysteine, riboflavin, and homocysteine concentrations were measured in fasting serum from 224 incident RCC cases and 224 controls (matched on age and date of serum collection). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders.

Results

Serum folate tended to be inversely associated with RCC, compared to the first quartile, the odds ratios (95% CI) for subsequent quartiles were 0.62 (0.35–1.08), 0.52 (0.29–0.93), and 0.67 (0.37–1.20) (P-trend = 0.19). When modeled as a threshold effect, subjects in the lowest serum folate quartile (≤6.64 nmol/l), which corresponds to deficient folate status, had a significant increased RCC risk (OR = 1.68, 95% CI 1.06–2.65) compared to those with higher serum folate. The other one-carbon metabolism biomarkers were not associated with RCC.

Conclusions

This study in male smokers suggests that deficient folate status may increase risk of RCC, but confirmation is needed in other epidemiologic studies that include women and non-smokers.

Keywords

Folate Renal cell carcinoma Biological markers Nested case–control study B vitamins 

References

  1. 1.
    Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr (1999) Rising incidence of renal cell cancer in the United States. JAMA 281:1628–1631CrossRefPubMedGoogle Scholar
  2. 2.
    Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Eisner MP, Horner MJ, Howlader N, Hayat M, Hankey BF, Edwards BK (eds) (http://seer.cancer.gov/csr/1975_2004/ based on November 2006 SEER data submission, posted to the SEER web site 2007) SEER Cancer Statistics Review, 1975-2004. Bethesda, MD: National Cancer Institute
  3. 3.
    Lipworth L, Tarone RE, McLaughlin JK (2006) The epidemiology of renal cell carcinoma. J Urol 176:2353–2358CrossRefPubMedGoogle Scholar
  4. 4.
    McLaughlin JK, Lindblad P, Mellemgaard A et al (1995) International renal-cell cancer study I. Tobacco use. Int J Cancer 60:194–198Google Scholar
  5. 5.
    McLaughlin JK, Lipworth L (2000) Epidemiologic aspects of renal cell cancer. Semin Oncol 27:115–123PubMedGoogle Scholar
  6. 6.
    Moore LE, Wilson RT, Campleman SL (2005) Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest 23:240–255CrossRefPubMedGoogle Scholar
  7. 7.
    Lee JE, Giovannucci E, Smith-Warner SA, Spiegelman D, Willett WC, Curhan GC (2006) Intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer. Cancer Epidemiol Biomarkers Prev 15:2445–2452CrossRefPubMedGoogle Scholar
  8. 8.
    Rashidkhani B, Lindblad P, Wolk A (2005) Fruits, vegetables and risk of renal cell carcinoma: a prospective study of Swedish women. Int J Cancer 113:451–455CrossRefPubMedGoogle Scholar
  9. 9.
    van Dijk BA, Schouten LJ, Kiemeney LA, Goldbohm RA, van den Brandt PA (2005) Vegetable and fruit consumption and risk of renal cell carcinoma: results from the Netherlands Cohort Study. Int J Cancer 117:648–654CrossRefPubMedGoogle Scholar
  10. 10.
    Weikert S, Boeing H, Pischon T, Olsen A, Tjonneland A et al (2006) Fruits and vegetables and renal cell carcinoma: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 118:3133–3139CrossRefPubMedGoogle Scholar
  11. 11.
    Bertoia M, Albanes D, Mayne ST, Mannisto S, Virtamo J, Wright ME (2009) No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma. Int J CancerGoogle Scholar
  12. 12.
    Lee JE, Mannisto S, Spiegelman D et al (2009) Intakes of fruit, vegetables, and carotenoids and renal cell cancer risk: a pooled analysis of 13 prospective studies. Cancer Epidemiol Biomarkers Prev 18:1730–1739CrossRefPubMedGoogle Scholar
  13. 13.
    Stover PJ (2004) Physiology of folate and vitamin B12 in health and disease. Nutr Rev 62:12 (discussion S13)CrossRefGoogle Scholar
  14. 14.
    Friso S, Choi SW (2005) Gene-nutrient interactions in one-carbon metabolism. Curr Drug Metab 6:37–46CrossRefPubMedGoogle Scholar
  15. 15.
    Bailey LB, Gregory JF III (1999) Folate metabolism and requirements. J Nutr 129:779–782PubMedGoogle Scholar
  16. 16.
    Clarke S, Banfield K (2001) S-adenosylmethionine-dependent methyltransferases. In: Carmel R, Jacobson DW (eds) Homocysteine in health and disease. Cambridge Press, CambridgeGoogle Scholar
  17. 17.
    Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI (2007) The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 113:234–258CrossRefPubMedGoogle Scholar
  18. 18.
    Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132PubMedGoogle Scholar
  19. 19.
    Kim Y-I (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88CrossRefPubMedGoogle Scholar
  20. 20.
    Kim Y-I (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292CrossRefPubMedGoogle Scholar
  21. 21.
    Larsson SC, Giovannucci E, Wolk A (2006) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131:1271–1283CrossRefPubMedGoogle Scholar
  22. 22.
    World Cancer Research/Fund/American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. AICR, Washington, DCGoogle Scholar
  23. 23.
    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 91:535–541CrossRefPubMedGoogle Scholar
  24. 24.
    Moore LE, Hung R, Karami S, Boffetta P, Berndt S, Hsu CC (2008) Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer 122:1710–1715CrossRefPubMedGoogle Scholar
  25. 25.
    The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group (1994) The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol 4:1–10CrossRefGoogle Scholar
  26. 26.
    Korhonen P, Malila N, Pukkala E, Teppo L, Albanes D, Virtamo J (2002) The Finnish cancer registry as follow-up source of a large trial cohort—accuracy and delay. Acta Oncol 41:381–388CrossRefPubMedGoogle Scholar
  27. 27.
    Shin-Buehring Y, Rasshofer R, Endres WA (1981) A new enzymatic method for pyridoxal-5′ phosphate determination. J Inherit Metab Disorders 4:123–124CrossRefGoogle Scholar
  28. 28.
    Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422:43–52CrossRefPubMedGoogle Scholar
  29. 29.
    Zempleni J, Link G, Kübler W (1992) The transport of thiamine, riboflavin and pyridoxal 5′-phosphate by human placenta. Int J Vitam Nutr Res 62:165–172PubMedGoogle Scholar
  30. 30.
    Fears TR, Ziegler RG, Donaldson JL et al (2002) Reproducibility studies and interlaboratory concordance for androgen assays of male plasma hormone levels. Cancer Epidemiol Biomarkers Prev 11:785–789PubMedGoogle Scholar
  31. 31.
    Pietinen P, Hartman AM, Haapa E et al (1988) Reproducibility and validity of dietary assessment instruments: I. A self-administered food use questionnaire with a portion size picture booklet. Am. J. Epidemiol. 128:655–666Google Scholar
  32. 32.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27PubMedGoogle Scholar
  33. 33.
    Mason JB (2003) Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr 133:941S–947SPubMedGoogle Scholar
  34. 34.
    Kim Y-I (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17:2220–2225CrossRefPubMedGoogle Scholar
  35. 35.
    Ulrich CM (2008) Folate and cancer prevention—where to next? Counterpoint. Cancer Epidemiol Biomarkers Prev 17:2226–2230CrossRefPubMedGoogle Scholar
  36. 36.
    Alfthan G, Laurinen MS, Valsta LM, Pastinen T, Aro A (2003) Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur J Clin Nutr 57:81–88CrossRefPubMedGoogle Scholar
  37. 37.
    Brevik A, Vollset SE, Tell GS et al (2005) Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: The Hordaland Homocysteine Study. Am J Clin Nutr 81:434–439PubMedGoogle Scholar
  38. 38.
    Dietrich M, Brown CJ, Block G (2005) The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J Am Coll Nutr 24:266–274PubMedGoogle Scholar
  39. 39.
    Frosst P, Blom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113CrossRefPubMedGoogle Scholar
  40. 40.
    Herbert V (1998) Folic acid. In: Shils M, Olson J, Shike M, Ross AC (eds) Modern nutrition in health and disease, 9th edn. Williams, Wilkins, Baltimore, pp 443–446Google Scholar
  41. 41.
    Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698CrossRefPubMedGoogle Scholar
  42. 42.
    Mannino DM, Mulinare J, Ford ES, Schwartz J (2003) Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey. Nicotine Tob Res 5:357–362CrossRefPubMedGoogle Scholar
  43. 43.
    Gabriel HE, Crott JW, Ghandour H et al (2006) Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. Am J Clin Nutr 83:835–841PubMedGoogle Scholar
  44. 44.
    Piyathilake CJ, Macaluso M, Hine RJ, Richards EW, Krumdieck CL (1994) Local and systemic effects of cigarette smoking on folate and vitamin B-12. Am J Clin Nutr 60:559–566PubMedGoogle Scholar
  45. 45.
    Pfeiffer CM, Johnson CL, Jain RB et al (2007) Trends in blood folate and vitamin B-12 concentrations in the United States, 1988 2004. Am J Clin Nutr 86:718–727PubMedGoogle Scholar

Copyright information

© US Government 2010

Authors and Affiliations

  • Todd M. Gibson
    • 1
    • 2
  • Stephanie J. Weinstein
    • 2
  • Susan T. Mayne
    • 1
  • Ruth M. Pfeiffer
    • 2
  • Jacob Selhub
    • 3
  • Philip R. Taylor
    • 2
  • Jarmo Virtamo
    • 4
  • Demetrius Albanes
    • 2
  • Rachael Stolzenberg-Solomon
    • 2
  1. 1.Yale School of Public HealthNew HavenUSA
  2. 2.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of Health, Department of Health and Human ServicesRockvilleUSA
  3. 3.Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  4. 4.Department of Health Promotion and Chronic Disease PreventionNational Public Health InstituteHelsinkiFinland

Personalised recommendations