Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Causes & Control
Published in: Cancer Causes & Control 7/2010

01-07-2010 | Original paper

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

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

Published in: Cancer Causes & Control | Issue 7/2010

Login to get access

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.
Literature
1.
Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr (1999) Rising incidence of renal cell cancer in the United States. JAMA 281:1628–1631CrossRefPubMed
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.
Lipworth L, Tarone RE, McLaughlin JK (2006) The epidemiology of renal cell carcinoma. J Urol 176:2353–2358CrossRefPubMed
4.
McLaughlin JK, Lindblad P, Mellemgaard A et al (1995) International renal-cell cancer study I. Tobacco use. Int J Cancer 60:194–198
5.
McLaughlin JK, Lipworth L (2000) Epidemiologic aspects of renal cell cancer. Semin Oncol 27:115–123PubMed
6.
Moore LE, Wilson RT, Campleman SL (2005) Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest 23:240–255CrossRefPubMed
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 15:2445–2452CrossRefPubMed
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 113:451–455CrossRefPubMed
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 117:648–654CrossRefPubMed
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 118:3133–3139CrossRefPubMed
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 Cancer
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 18:1730–1739CrossRefPubMed
13.
Stover PJ (2004) Physiology of folate and vitamin B12 in health and disease. Nutr Rev 62:12 (discussion S13)CrossRef
14.
Friso S, Choi SW (2005) Gene-nutrient interactions in one-carbon metabolism. Curr Drug Metab 6:37–46CrossRefPubMed
15.
Bailey LB, Gregory JF III (1999) Folate metabolism and requirements. J Nutr 129:779–782PubMed
16.
Clarke S, Banfield K (2001) S-adenosylmethionine-dependent methyltransferases. In: Carmel R, Jacobson DW (eds) Homocysteine in health and disease. Cambridge Press, Cambridge
17.
Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI (2007) The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 113:234–258CrossRefPubMed
18.
Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132PubMed
19.
Kim Y-I (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88CrossRefPubMed
20.
Kim Y-I (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292CrossRefPubMed
21.
Larsson SC, Giovannucci E, Wolk A (2006) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131:1271–1283CrossRefPubMed
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, DC
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 91:535–541CrossRefPubMed
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 122:1710–1715CrossRefPubMed
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 4:1–10CrossRef
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 41:381–388CrossRefPubMed
27.
Shin-Buehring Y, Rasshofer R, Endres WA (1981) A new enzymatic method for pyridoxal-5′ phosphate determination. J Inherit Metab Disorders 4:123–124CrossRef
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 422:43–52CrossRefPubMed
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 62:165–172PubMed
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 11:785–789PubMed
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. 128:655–666
32.
Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27PubMed
33.
Mason JB (2003) Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr 133:941S–947SPubMed
34.
Kim Y-I (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17:2220–2225CrossRefPubMed
35.
Ulrich CM (2008) Folate and cancer prevention—where to next? Counterpoint. Cancer Epidemiol Biomarkers Prev 17:2226–2230CrossRefPubMed
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 57:81–88CrossRefPubMed
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 81:434–439PubMed
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 24:266–274PubMed
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 10:111–113CrossRefPubMed
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 443–446
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 270:2693–2698CrossRefPubMed
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 5:357–362CrossRefPubMed
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 83:835–841PubMed
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 60:559–566PubMed
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 86:718–727PubMed
Metadata
Title
A prospective study of one-carbon metabolism biomarkers and risk of renal cell carcinoma
Authors
Todd M. Gibson
Stephanie J. Weinstein
Susan T. Mayne
Ruth M. Pfeiffer
Jacob Selhub
Philip R. Taylor
Jarmo Virtamo
Demetrius Albanes
Rachael Stolzenberg-Solomon
Publication date
01-07-2010
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 7/2010
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-010-9534-5

Other articles of this Issue 7/2010

Cancer Causes & Control 7/2010 Go to the issue

Original paper

History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study

Original paper

Racial differences in PSA screening interval and stage at diagnosis

Brief report

A case–control study of tobacco use and other non-occupational risk factors for lymphoma subtypes defined by t(14; 18) translocations and bcl-2 expression

Original paper

Dietary patterns and risk of advanced prostate cancer: a principal component analysis in Uruguay

Original paper

Cancer risk in DES daughters

Original paper

Meeting the cervical cancer screening needs of underserved women: The National Breast and Cervical Cancer Early Detection Program, 2004–2006
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits