Low-density lipoprotein cholesterol and the risk of cancer: A mendelian randomization study

Journal of the National Cancer Institute

Volumn 103, Issue 6, 2011, Pages 508-519

  Benn, Marianne ^a,d   Tybjærg Hansen, Anne ^a,b,c,d   Stender, Stefan ^b,d   Frikke Schmidt, Ruth ^a,b,d   Nordestgaard, Børge G ^a,c,d  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b Rigshospitalet   (Denmark)

^c BISPEBJERG HOSPITAL   (Denmark)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; ABC TRANSPORTER G8; ANTIDIABETIC AGENT; ANTIHYPERTENSIVE AGENT; ANTILIPEMIC AGENT; APOLIPOPROTEIN E; ARGININE; ASPARTIC ACID; CYSTEINE; HISTIDINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LEUCINE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PROTEIN PCSK9; SERINE PROTEINASE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ADULT; AGED; AMINO ACID SUBSTITUTION; ANTIHYPERTENSIVE THERAPY; ANUS CANCER; ARTICLE; BILIARY TRACT CANCER; BLADDER CANCER; BODY MASS; BREAST CANCER; CANCER DIAGNOSIS; CANCER RISK; CHOLESTEROL BLOOD LEVEL; COLON CANCER; COLORIMETRY; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DIABETES MELLITUS; DIGESTIVE SYSTEM CANCER; ESOPHAGUS CANCER; FEMALE; GENETIC ASSOCIATION; GENOTYPE; HAZARD RATIO; HEMATOLOGIC MALIGNANCY; HISTOPATHOLOGY; HODGKIN DISEASE; HUMAN; HYPERTENSION; ISCHEMIC HEART DISEASE; KIDNEY CANCER; LARYNX CANCER; LEUKEMIA; LIVER CANCER; LUNG CANCER; MAJOR CLINICAL STUDY; MALE; MENDELIAN RANDOMIZATION ANALYSIS; MOUTH CANCER; MULTIPLE MYELOMA; NEOPLASM; NONHODGKIN LYMPHOMA; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; RECTUM CANCER; RESPIRATORY TRACT CANCER; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; SMALL INTESTINE CANCER; STOMACH CANCER; TESTIS CANCER; TRIACYLGLYCEROL BLOOD LEVEL; UTERINE CERVIX CANCER; VAGINA CANCER;

ADULT; AGED; APOLIPOPROTEINS E; ATP-BINDING CASSETTE TRANSPORTERS; CHOLESTEROL, LDL; DENMARK; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENOTYPE; HUMANS; MALE; MENDELIAN RANDOMIZATION ANALYSIS; MIDDLE AGED; NEOPLASMS; ODDS RATIO; POLYMORPHISM, SINGLE NUCLEOTIDE; PROPORTIONAL HAZARDS MODELS; PROSPECTIVE STUDIES; RISK ASSESSMENT; RISK FACTORS; SERINE ENDOPEPTIDASES; TUMOR MARKERS, BIOLOGICAL;

EID: 79952843139     PISSN: 00278874     EISSN: 14602105     Source Type: Journal    
DOI: 10.1093/jnci/djr008     Document Type: Article

References (46)

1. Rose G, Blackburn H, Keys A, et al. Colon cancer and blood-cholesterol. Lancet. 1974;1(7850):181-183.
2. Strasak AM, Pfeiffer RM, Brant LJ, et al. Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol. 2009; 20(6):1113-1120.
3. Jacobs D, Blackburn H, Higgins M, et al. Report of the conference on low blood cholesterol: mortality associations. Circulation. 1992;86(3): 1046-1060.
4. Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control. 1991;2(4):253-261.
5. Sherwin RW, Wentworth DN, Cutler JA, et al. Serum cholesterol levels and cancer mortality in 361662 men screened for the multiple risk factor intervention trial. JAMA. 1987;257(7):943-948. (Pubitemid 17024387)
6. Neaton JD, Blackburn H, Jacobs D, et al. Serum cholesterol level and mortality fndings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152(7):1490-1500.
7. Kritchevsky SB, Wilcosky TC, Morris DL, Truong KN, Tyroler HA. Changes in plasma lipid and lipoprotein cholesterol and weight prior to the diagnosis of cancer. Cancer Res. 1991;51(12):3198-3203.
8. Peto R, Emberson J, Landray M, et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008;359(13):1357-1366.
9. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA. 1996;275(1):55-60. (Pubitemid 26004257)
10. Oliver MF, Heady JA, Morris JN, Cooper J. A co-operative trial in the primary prevention of ischaemic heart disease using clofbrate. Report from the Committee of Principal Investigators. Br Heart J. 1978;40(10):1069-1118.
11. Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008; 359(13):1343-1356.
12. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133-1163. (Pubitemid 351395448)
13. Burgess S, Thompson SG, Burgess S, et al. Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables. Stat Med. 2010;29(12):1298-1311.
14. Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33(1):30-42. (Pubitemid 38528650)
15. Palmer TM, Thompson JR, Tobin MD, Sheehan NA, Burton PR. Adjusting for bias and unmeasured confounding in Mendelian randomization studies with binary responses. Int J Epidemiol. 2008;37(5): 1161-1168.
16. Thanassoulis G, O'Donnell CJ. Mendelian randomization: nature's randomized trial in the post-genome era. JAMA. 2009;301(22):2386-2388.
17. Tobin MD, Minelli C, Burton PR, Thompson JR. Commentary: development of Mendelian randomization: from hypothesis test to 'Mendelian deconfounding'. Int J Epidemiol. 2004;33(1):26-29. (Pubitemid 38500151)
18. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299-308. (Pubitemid 47080484)
19. Zacho J, Tybjaerg-Hansen A, Jensen JS, et al. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008; 359(18):1897-1908.
20. Storm HH, Michelsen EV, Clemmensen IH, Pihl J. The Danish Cancer Registry-history, content, quality and use. Dan Med Bull. 1997;44(5): 535-539.
21. Storm HH. Completeness of cancer registration in Denmark 1943-1966 and effcacy of record linkage procedures. Int J Epidemiol. 1988;17(1):44-49.
22. World Health Organization. Third Report of the Expert Committee on Health Statistics. 53. Geneva, Switzerland: World Health Organization; 1952.
23. World Health Organization. International Classifcation of Diseases and Related Health Problems, 10th Revision. Geneva, Switzerland: World Health Organization; 2004.
24. Benn M, Nordestgaard BG, Grande P, Schnohr P, Tybjaerg-Hansen A. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol. 2010;55(25):2833-2842.
25. Stender S, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A. Sterol transporter ABCG8, gallstones, and biliary cancer in 62,000 individuals from the general population. Hepatology. 2010. doi: 10.1002/ hep.24046.
26. Frikke-Schmidt R, Tybjaerg-Hansen A, Steffensen R, Jensen G, Nordestgaard BG. Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease: the Copenhagen City Heart Study. J Am Coll Cardiol. 2000; 35(5):1192-1199. (Pubitemid 30206894)
27. 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(6):499-502.
28. Whitworth JA. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21(11):1983-1992. (Pubitemid 38296854)
29. World Health Organization. Defnition, Diagnosis and Classifcation of Diabetes Mellitus and its Complications. Report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 1999.
30. World Health Organization. International Classifcation of Diseases and Related Health Problems, 8th Revision. Geneva, Switzerland: World Health Organization; 1965.
31. Frikke-Schmidt R, Nordestgaard BG, Agerholm-Larsen B, Schnohr P, Tybjaerg-Hansen A. Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype. J Lipid Res. 2000;41(11):1812-1822.
32. Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69(1):239-241.
33. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation 2002; 106 (25): 3143.
34. Clarke R, Shipley M, Lewington S, et al. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol. 1999;150(4):341-353. (Pubitemid 29383482)
35. Cuzick J. A Wilcoxon-type test for trend. Stat Med. 1985;4(1):87-90. (Pubitemid 15142530)
36. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326(7382):219. (Pubitemid 36143396)
37. Hamilton-Craig I, Kostner K, Colquhoun D, Woodhouse S. At sea with SEAS: the frst clinical endpoint trial for ezetimibe, treatment of patients with mild to moderate aortic stenosis, ends with mixed results and more controversy. Heart Lung Circ. 2009;18(5):343-346.
38. Folsom AR, Peacock JM, Boerwinkle E. Sequence variation in proprotein convertase subtilisin/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2455-2458. (Pubitemid 351196380)
39. Trompet S, Jukema JW, Katan MB, et al. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study. Am J Epidemiol. 2009;170(11):1415-1421.
40. Gilbert HS, Ginsberg H, Fagerstrom R, Brown WV. Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity. Am J Med. 1981;71(4):595-602. (Pubitemid 12140427)
41. Vitols S, Gahrton G, Bjorkholm M, Peterson C. Hypocholesterolaemia in malignancy due to elevated low-density-lipoprotein-receptor activity in tumour cells: evidence from studies in patients with leukaemia. Lancet. 1985;2(8465):1150-1154.
42. Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466(7307):707- 713.
43. Tybjærg-Hansen A, Steffensen R, Meinertz H, Schnohr P, Nordestgaard BG. Association of mutations in the apolipoprotein B gene with hypercho-lesterolemia and the risk of ischemic heart disease. N Engl J Med. 1998; 338(22):1577-1584. (Pubitemid 28243987)
44. Tybjærg-Hansen A, Jensen HK, Benn M, et al. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identifed in different background populations. Arterioscler Thromb Vasc Biol. 2005;25(1):211-215. (Pubitemid 40054278)
45. Angelopoulos TJ, Lowndes J. ApoE genotype: impact on health, ftness and nutrition. World Rev Nutr Diet. 2008;98:77-93.
46. Frikke-Schmidt R, Nordestgaard BG, Thudium D, Moes Gronholdt ML, Tybjaerg-Hansen A. APOE genotype predicts AD and other dementia but not ischemic cerebrovascular disease. Neurology. 2001;56(2):194-200. (Pubitemid 32095360)