European Journal of Epidemiology

, Volume 29, Issue 2, pp 119–132 | Cite as

Prospective associations between serum biomarkers of lipid metabolism and overall, breast and prostate cancer risk

  • Mathilde His
  • Laurent Zelek
  • Mélanie Deschasaux
  • Camille Pouchieu
  • Emmanuelle Kesse-Guyot
  • Serge Hercberg
  • Pilar Galan
  • Paule Latino-Martel
  • Jacques Blacher
  • Mathilde Touvier


Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994–2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR1mmol/L increment = 0.91, 95 % CI 0.82–1.00; P = 0.04) and breast (HR1mmol/L increment = 0.83, 95 % CI 0.69–0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR1mmol/L increment = 0.61, 95 % CI 0.46–0.82; P = 0.0008) and breast (HR1mmol/L increment = 0.48, 95 % CI 0.28–0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR1g/L increment = 0.56, 95 % CI 0.39–0.82; P = 0.003) and breast (HR1g/L increment = 0.36, 95 % CI 0.18–0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention.


Prospective study Neoplasms Breast neoplasms Cholesterol High-density lipoprotein Apolipoprotein A1 



Apolipoprotein A1


Apolipoprotein B


Body mass index


Confidence interval


High density lipoprotein cholesterol


Hazard ratio


Low density lipoprotein cholesterol




Supplémentation en Vitamines et Minéraux Antioxydants


Total cholesterol



The authors thank Gwenael Monot, Younes Esseddik, Paul Flanzy, Mohand Ait Oufella, Yasmina Chelghoum, and Than Duong Van (computer scientists), Florence Charpentier (dietitian), Nathalie Arnault, Véronique Gourlet, Fabien Szabo, Laurent Bourhis, and Stephen Besseau (statisticians), and Rachida Mehroug (logistics assistant) for their technical contribution to the SU.VI.MAX study. This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM U557); the Institut National de la Recherche Agronomique (INRA U1125); and the Université Paris 13.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Huxley R, Lewington S, Clarke R. Cholesterol, coronary heart disease and stroke: a review of published evidence from observational studies and randomized controlled trials. Semin Vasc Med. 2002;2:315–23.PubMedCrossRefGoogle Scholar
  2. 2.
    Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control. 1991;2:253–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Melvin JC, Holmberg L, Rohrmann S, et al. Serum lipid profiles and cancer risk in the context of obesity: four meta-analyses. J Cancer Epidemiol. 2013;2013:823849.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Bjorge T, Lukanova A, Tretli S, et al. Metabolic risk factors and ovarian cancer in the metabolic syndrome and cancer project. Int J Epidemiol. 2011;40:1667–77.PubMedCrossRefGoogle Scholar
  5. 5.
    Eichholzer M, Stahelin HB, Gutzwiller F, et al. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study. Am J Clin Nutr. 2000;71:569–74.PubMedGoogle Scholar
  6. 6.
    Nago N, Ishikawa S, Goto T, et al. Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study. J Epidemiol. 2011;21:67–74.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Strohmaier S, Edlinger M, Manjer J, et al. Total serum cholesterol and cancer incidence in the metabolic syndrome and cancer project (Me-Can). PLoS One. 2013;8:e54242.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Kitahara CM, de Berrington GA, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol. 2011;29:1592–8.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Iso H, Ikeda A, Inoue M, et al. Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts. Int J Cancer. 2009;125:2679–86.PubMedCrossRefGoogle Scholar
  10. 10.
    Jacobs EJ, Gapstur SM. Cholesterol and cancer: answers and new questions. Cancer Epidemiol Biomarkers Prev. 2009;18:2805–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Henriksson P, Eriksson M, Ericsson S, et al. Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate. Lancet. 1989;2:1178–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Vitols S, Gahrton G, Bjorkholm M, et al. Hypocholesterolaemia in malignancy due to elevated low-density-lipoprotein-receptor activity in tumour cells: evidence from studies in patients with leukaemia. Lancet. 1985;2:1150–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Dessi S, Batetta B, Pulisci D, et al. Altered pattern of lipid metabolism in patients with lung cancer. Oncology. 1992;49:436–41.PubMedCrossRefGoogle Scholar
  14. 14.
    Ahn J, Lim U, Weinstein SJ, et al. Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2814–21.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Soran H, Hama S, Yadav R, et al. HDL functionality. Curr Opin Lipidol. 2012;23:353–66.PubMedCrossRefGoogle Scholar
  16. 16.
    von Eckardstein A, Hersberger M, Rohrer L. Current understanding of the metabolism and biological actions of HDL. Curr Opin Clin Nutr Metab Care. 2005;8:147–52.CrossRefGoogle Scholar
  17. 17.
    Agnoli C, Berrino F, Abagnato CA, et al. Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: a nested case–control study. Nutr Metab Cardiovasc Dis. 2010;20:41–8.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Furberg AS, Veierod MB, Wilsgaard T, et al. Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk. J Natl Cancer Inst. 2004;96:1152–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Gaard M, Tretli S, Urdal P. Risk of breast cancer in relation to blood lipids: a prospective study of 31,209 Norwegian women. Cancer Causes Control. 1994;5:501–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Hoyer AP, Engholm G. Serum lipids and breast cancer risk: a cohort study of 5,207 Danish women. Cancer Causes Control. 1992;3:403–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Inoue M, Noda M, Kurahashi N, et al. Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan. Eur J Cancer Prev. 2009;18:240–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kucharska-Newton AM, Rosamond WD, Mink PJ, et al. HDL-cholesterol and incidence of breast cancer in the ARIC cohort study. Ann Epidemiol. 2008;18:671–7.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Melvin JC, Seth D, Holmberg L, et al. Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study. Cancer Epidemiol Biomarkers Prev. 2012;21:1381–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Moorman PG, Hulka BS, Hiatt RA, et al. Association between high-density lipoprotein cholesterol and breast cancer varies by menopausal status. Cancer Epidemiol Biomarkers Prev. 1998;7:483–8.PubMedGoogle Scholar
  25. 25.
    Esposito K, Chiodini P, Capuano A, et al. Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause. 2013;20:1301–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Mondul AM, Weinstein SJ, Virtamo J, et al. Serum total and HDL cholesterol and risk of prostate cancer. Cancer Causes Control. 2011;22:1545–52.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Van Hemelrijck M, Walldius G, Jungner I, et al. Low levels of apolipoprotein A-I and HDL are associated with risk of prostate cancer in the Swedish AMORIS study. Cancer Causes Control. 2011;22:1011–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Esposito K, Chiodini P, Capuano A, et al. Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis. J Endocrinol Invest. 2013;36:132–9.PubMedGoogle Scholar
  29. 29.
    Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Stamey TA. Second Stanford conference on international standardization of prostate-specific antigen immunoassays: September 1 and 2, 1994. Urology. 1995;45:173–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Le Moullec N, Deheeger M, Preziosi P, et al. Validation du manuel photos utilisé pour l’enquête alimentaire de l’étude SU.VI.MAX. Cah Nutr Diet. 1996;31:158–64.Google Scholar
  32. 32.
    Hercberg S. Table de composition SU.VI.MAX des aliments. Paris: Les éditions INSERM/Economica; 2005.Google Scholar
  33. 33.
    Kritchevsky SB, Wilcosky TC, Morris DL, et al. Changes in plasma lipid and lipoprotein cholesterol and weight prior to the diagnosis of cancer. Cancer Res. 1991;51:3198–203.PubMedGoogle Scholar
  34. 34.
    Planella T, Cortes M, Martinez-Bru C, et al. Calculation of LDL-cholesterol by using apolipoprotein B for classification of nonchylomicronemic dyslipemia. Clin Chem. 1997;43:808–15.PubMedGoogle Scholar
  35. 35.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMedGoogle Scholar
  36. 36.
    Huang R, Silva RA, Jerome WG, et al. Apolipoprotein A–I structural organization in high-density lipoproteins isolated from human plasma. Nat Struct Mol Biol. 2011;18:416–22.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Aleksandrova K, Boeing H, Jenab M, et al. Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study. Cancer Prev Res (Phila). 2011;4:1873–83.CrossRefGoogle Scholar
  38. 38.
    Esposito K, Chiodini P, Capuano A, et al. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine. 2013;. doi: 10.1007/s12020-013-9973-3.Google Scholar
  39. 39.
    Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Schatzkin A, Hoover RN, Taylor PR, et al. Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. Lancet. 1987;2:298–301.PubMedCrossRefGoogle Scholar
  41. 41.
    Cleeman JI, Grundy SM, Becker D, Clark LT. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III). Jama. 2001;285:2486–97.Google Scholar
  42. 42.
    Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc. 2001;33:S502–15.PubMedCrossRefGoogle Scholar
  43. 43.
    World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington, DC: AICR; 2007.Google Scholar
  44. 44.
    Kraus WE, Houmard JA, Duscha BD, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347:1483–92.PubMedCrossRefGoogle Scholar
  45. 45.
    Esteve E, Ricart W, Fernandez-Real JM. Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutr. 2005;24:16–31.PubMedCrossRefGoogle Scholar
  46. 46.
    Beynen AC, Katan MB, Van Zutphen LF. Hypo- and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in diet. Adv Lipid Res. 1987;22:115–71.PubMedGoogle Scholar
  47. 47.
    Ordovas JM, Lopez-Miranda J, Mata P, et al. Gene-diet interaction in determining plasma lipid response to dietary intervention. Atherosclerosis. 1995;118(Suppl.):S11–27.PubMedCrossRefGoogle Scholar
  48. 48.
    Al-Delaimy WK, Jansen EH, Peeters PH, et al. Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts. Biomarkers. 2006;11:370–82.PubMedCrossRefGoogle Scholar
  49. 49.
    Bairaktari E, Hatzidimou K, Tzallas C, et al. Estimation of LDL cholesterol based on the Friedewald formula and on apo B levels. Clin Biochem. 2000;33:549–55.PubMedCrossRefGoogle Scholar
  50. 50.
    Binder-Foucard F, Belot A, Delafosse P, et al. National estimate of the incidence and mortality from cancer in France between 1980 and 2012. Part 1—solid tumors. Saint-Maurice: Institut de veille sanitaire; 2013.Google Scholar
  51. 51.
    Anderson KM, Odell PM, Wilson PW, et al. Cardiovascular disease risk profiles. Am Heart J. 1991;121:293–8.PubMedCrossRefGoogle Scholar
  52. 52.
    World Health Organization. Cardiovascular diseases (CVDs). Fact sheet no. 317. In: Media centre. World Health Organization; 2013. Accessed 12 July 2013.
  53. 53.
    World Health Organization. Cancer. Fact sheet no. 297. In: Media centre. World Health Organization. 2013. Accessed July 12 2013.

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Mathilde His
    • 1
  • Laurent Zelek
    • 1
    • 2
  • Mélanie Deschasaux
    • 1
  • Camille Pouchieu
    • 1
  • Emmanuelle Kesse-Guyot
    • 1
  • Serge Hercberg
    • 1
    • 3
  • Pilar Galan
    • 1
  • Paule Latino-Martel
    • 1
  • Jacques Blacher
    • 1
    • 4
  • Mathilde Touvier
    • 1
  1. 1.EREN, SMBH Paris 13Sorbonne Paris Cité Research Center, Nutritional Epidemiology Research Team, Inserm (U1153), Inra, Cnam, Paris 13 UniversityBobigny CedexFrance
  2. 2.Oncology DepartmentAvicenne HospitalBobigny CedexFrance
  3. 3.Public Health DepartmentAvicenne HospitalBobigny CedexFrance
  4. 4.Diagnosis and Therapeutic CenterHôtel-Dieu HospitalParisFrance

Personalised recommendations