Abstract
Background/Objectives:
Evidence on the role of diet in relation to prostate cancer progression is sparse. Foods rich in lignans have shown beneficial effects on prostate cancer progression in both animal studies and small human intervention studies, including beneficial effects on prostate-specific antigen levels and tumour growth. The lignan metabolite, enterolactone, has further shown to slow prostate cancer cell growth in vitro. The aim was to investigate the association between prediagnostic enterolactone concentrations and mortality among men with prostate cancer.
Subljects/Methods:
Prediagnostic plasma concentrations of enterolactone from 1390 men diagnosed with prostate cancer from the Danish Diet, Cancer and Health cohort were related to all-cause or prostate cancer-specific death, using Cox proportional hazards models with follow-up time (from the date of diagnose until the date of death, emigration or end of follow-up by December 2013) as the underlying time axis.
Results:
The hazard ratios for enterolactone concentrations assessed linearly by 20 nmol/l increments was 0.95 (0.90, 1.02) for all-cause mortality and 0.98 (0.92, 1.05) for prostate cancer-specific mortality. Categorisation of enterolactone concentrations into quartiles did not reveal a different pattern. No effect modifications by smoking, body mass index or sport were observed, and the associations did not differ by prostate cancer aggressiveness.
Conclusions:
We found no association between enterolactone concentrations and mortality among men diagnosed with prostate cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
NORDCAN: Cancer Incidence, Mortality, Prevalence and Survival in the Nordic Countries [Internet]. Association of the Nordic Cancer Registries. Danish Cancer Society, 2014 [cited 09.04.2015].
Abbas F, Scardino PT . The natural history of clinical prostate carcinoma. Cancer 1997; 80: 827–833.
Popiolek M, Rider JR, Andren O, Andersson SO, Holmberg L, Adami HO et al. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur Urol 2013; 63: 428–435.
Borre M, Nerstrom B, Overgaard J . The natural history of prostate carcinoma based on a Danish population treated with no intent to cure. Cancer 1997; 80: 917–928.
Adlercreutz H . Lignans and human health. Crit Rev Clin Lab Sci 2007; 44: 483–525.
Wang LQ . Mammalian phytoestrogens: enterodiol and enterolactone. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 777: 289–309.
Chen LH, Fang J, Sun Z, Li H, Wu Y, Demark-Wahnefried W et al. Enterolactone inhibits insulin-like growth factor-1 receptor signaling in human prostatic carcinoma PC-3 cells. J Nutr 2009; 139: 653–659.
McCann MJ, Rowland IR, Roy NC . Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis. Mol Nutr Food Res 2013; 57: 212–224.
Smeds AI, Eklund PC, Sjoholm RE, Willfor SM, Nishibe S, Deyama T et al. Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts. J Agric Food Chem 2007; 55: 1337–1346.
Bylund A, Lundin E, Zhang JX, Nordin A, Kaaks R, Stenman UH et al. Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer. Eur J Cancer Prev 2003; 12: 407–415.
Landberg R, Andersson SO, Zhang JX, Johansson JE, Stenman UH, Adlercreutz H et al. Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with prostate cancer. J Nutr 2010; 140: 2180–2186.
Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev 2008; 17: 3577–3587.
Tjonneland A, Olsen A, Boll K, Stripp C, Christensen J, Engholm G et al. Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: a population-based prospective cohort study of 57,053 men and women in Denmark. Scand J Public Health 2007; 35: 432–441.
Pedersen CB . The Danish Civil Registration System. Scand J Public Health 2011; 39: 22–25.
Gjerstorff ML . The Danish Cancer Registry. Scand J Public Health 2011; 39: 42–45.
Helweg-Larsen K . The Danish Register of Causes of Death. Scand J Public Health 2011; 39: 26–29.
Larsen SB, Brasso K, Iversen P, Christensen J, Christiansen M, Carlsson S et al. Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort. Eur J Cancer 2013; 49: 3041–3048.
Kilkkinen A, Pietinen P, Klaukka T, Virtamo J, Korhonen P, Adlercreutz H . Use of oral antimicrobials decreases serum enterolactone concentration. Am J Epidemiol 2002; 155: 472–477.
Kildemoes HW, Sorensen HT, Hallas J . The Danish National Prescription Registry. Scand J Public Health 2011; 39(7 Suppl): 38–41.
Norskov NP, Kyro C, Olsen A, Tjonneland A, Bach Knudsen KE . High-throughput LC-MS/MS method for direct quantification of glucuronidated, sulfated, and free enterolactone in human plasma. J Proteome Res 2016; 15: 1051–1058.
Kilkkinen A, Stumpf K, Pietinen P, Valsta LM, Tapanainen H, Adlercreutz H . Determinants of serum enterolactone concentration. Am J Clin Nutr 2001; 73: 1094–1100.
Storm HH, Michelsen EV, Clemmensen IH, Pihl J . The Danish Cancer Registry—history, content, quality and use. Dan Med Bull 1997; 44: 535–539.
Hedelin M, Klint A, Chang ET, Bellocco R, Johansson JE, Andersson SO et al. Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden). Cancer Causes Control 2006; 17: 169–180.
Stattin P, Bylund A, Biessy C, Kaaks R, Hallmans G, Adlercreutz H . Prospective study of plasma enterolactone and prostate cancer risk (Sweden). Cancer Causes Control 2004; 15: 1095–1102.
Heald CL, Ritchie MR, Bolton-Smith C, Morton MS, Alexander FE . Phyto-oestrogens and risk of prostate cancer in Scottish men. Br J Nutr 2007; 98: 388–396.
Peeters PH, Slimani N, van der Schouw YT, Grace PB, Navarro C, Tjonneland A et al. Variations in plasma phytoestrogen concentrations in European adults. J Nutr 2007; 137: 1294–1300.
Clavel T, Borrmann D, Braune A, Dore J, Blaut M . Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 2006; 12: 140–147.
Hullar MA, Lancaster SM, Li F, Tseng E, Beer K, Atkinson C et al. Enterolignan-producing phenotypes are associated with increased gut microbial diversity and altered composition in premenopausal women in the United States. Cancer Epidemiol Biomarkers Prev 2015; 24: 546–554.
Adgent MA, Rogan WJ . Triclosan and prescription antibiotic exposures and enterolactone production in adults. Environ Res 2015; 142: 66–71.
Zeleniuch-Jacquotte A, Adlercreutz H, Akhmedkhanov A, Toniolo P . Reliability of serum measurements of lignans and isoflavonoid phytoestrogens over a two-year period. Cancer Epidemiol Biomarkers Prev 1998; 7: 885–889.
Preston SH, Stokes A . Obesity paradox: conditioning on disease enhances biases in estimating the mortality risks of obesity. Epidemiology 2014; 25: 454–461.
Bylund A, Saarinen N, Zhang JX, Bergh A, Widmark A, Johansson A et al. Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo. Exp Biol Med (Maywood) 2005; 230: 217–223.
Bylund A, Zhang JX, Bergh A, Damber JE, Widmark A, Johansson A et al. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. Prostate 2000; 42: 304–314.
Wikstrom P, Bylund A, Zhang JX, Hallmans G, Stattin P, Bergh A . Rye bran diet increases epithelial cell apoptosis and decreases epithelial cell volume in TRAMP (transgenic adenocarcinoma of the mouse prostate) tumors. Nutr Cancer 2005; 53: 111–116.
Buck K, Zaineddin AK, Vrieling A, Linseisen J, Chang-Claude J . Meta-analyses of lignans and enterolignans in relation to breast cancer risk. Am J Clin Nutr 2010; 92: 141–153.
Seibold P, Vrieling A, Johnson TS, Buck K, Behrens S, Kaaks R et al. Enterolactone concentrations and prognosis after postmenopausal breast cancer: assessment of effect modification and meta-analysis. Int J Cancer 2014; 135: 923–933.
Acknowledgements
We thank Data Managers Katja Boll and Nick Martinussen for assistance with data preparation and Jytte Fogh Larsen for her administrative assistance. This study was funded by Innovation Fund Denmark, project ‘The effects of enterolignans in chronic diseases – ELIN’ (0603-00580B).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website
Supplementary information
Rights and permissions
About this article
Cite this article
Eriksen, A., Kyrø, C., Nørskov, N. et al. Prediagnostic enterolactone concentrations and mortality among Danish men diagnosed with prostate cancer. Eur J Clin Nutr 71, 1235–1240 (2017). https://doi.org/10.1038/ejcn.2017.42
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ejcn.2017.42