Advertisement

Cancer Causes & Control

, Volume 2, Issue 4, pp 253–261 | Cite as

Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies

  • M. R. Law
  • S. G. Thompson
Review

Data were analyzed from 33 prospective studies to assess the evidence for a long-term association of low serum cholesterol with cancer. In subjects with cancer diagnosed within two years of the cholesterol measurement or causing death within five years (n=4,661), the level of serum cholesterol was on average lower than in controls by 0.18 (SE=0.02) mmol/l in men and 0.11 (SE=0.04) mmol/l in women; this effect can be attributed to preclinical cancer. For cancers presenting after these intervals (n=22,030), the average differences were smaller but statistically significant (0.04 [SE=0.01] mmol/1 [P<0.001] in men, and 0.03 [SE=0.01] mmol/1 [P=0.005] in women), equivalent to about a 15 percent increase in cancer incidence in the lowest cholesterol quintile. This cannot be attributed entirely to preclinical cancer. In men, there was significant (P=0.01) heterogeneity between studies as to the extent of a long-term association. The heterogeneity could be substantially explained by socioeconomic status, the association being pronounced in studies of manual workers but absent in studies of professional men. The overall long-term association was attributable mainly to lung cancer in men, and partly to hemopoietic cancers (representing prolongation of survival by treatment). Colon cancer and other cancers unrelated to smoking showed no long-term association with low cholesterol. The data collectively do not justify concern that lowering serum cholesterol to reduce ischemic heart-disease risk might cause cancer. The long-term association with lung cancer is probably caused by smoking and we propose a mechanism.

Keywords

Public Health Cholesterol Lung Cancer Colon Cancer Socioeconomic Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sherwin RW, Wentworth DN, Cutler JA, Hulley SB, Kuller LH, Stamler J. Serum cholesterol levels and cancer mortality in 361662 men screened for the Multiple Risk Factor Intervention Trial. JAMA 1987; 257: 943–8.Google Scholar
  2. 2.
    Stemmermann GN, Chyou P-H, Kagan A, Nomura AMY, Yano K. Serum cholesterol and mortality among Japanese-American men: The Honolulu Heart Program. Arch Intern Med 1991; 151: 969–72Google Scholar
  3. 3.
    International Collaborative Group. Circulating cholesterol level and risk of death from cancer in men aged 40 to 69 years: experience of an international collaborative group. JAMA 1982; 248: 2853–9.Google Scholar
  4. 4.
    Keys A, Aravanis C, Blackburn H, et al. Serum cholesterol and cancer mortality in the Seven Countries Study. Am J Epidemiol 1985; 121: 870–83.Google Scholar
  5. 5.
    Yaari S, Goldbourt U, Evan-Zohar S, Neufeld HN. Associations of serum high density lipoprotein and total cholesterol with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10,000 men. Lancet 1981; i: 1011–5.Google Scholar
  6. 6.
    Shaper AG, Phillips AN, Pocock SJ. Plasma cholesterol, coronary heart disease and cancer. BMJ 1989; 298: 1381.Google Scholar
  7. 7.
    Dyer AR, Stamler J, Paul O, et al. Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J Chronic Dis 1981; 34: 249–60.Google Scholar
  8. 8.
    Davis CE, Knowles M, Kark J, Heyden S, Hames CG, Tyroler HA. Serum cholesterol levels and cancer mortality: Evans County twenty year follow-up study. In: Perkins EG, Visek WJ, eds. Dietary Fats and Health. Champaign, Illinois: American Oil Chemist's Society Monograph No. 10, 1982.Google Scholar
  9. 9.
    Garcia-Palmieri MR, Sorlie PD, Costas R, Havlik RJ. An apparent inverse relationship between serum cholesterol and cancer mortality in Puerto Rico. Am J Epidemiol 1981; 114: 29–40.Google Scholar
  10. 10.
    Salmond CE, Beaglehole R, Prior IAM. Are low cholesterol values associated with excess mortality? BMJ 1985 290: 422–4.Google Scholar
  11. 11.
    Tornberg SA, Holm LE, Carstensen JM. Eklund GA. Cancer incidence and cancer mortality in relation to serum cholesterol. JNCI 1989; 81: 1917–21.Google Scholar
  12. 12.
    Hiatt RA, Fireman BH. Serum cholesterol and the incidence of cancer in a large cohort. J Chronic Dis 1986; 39: 861–70.Google Scholar
  13. 13.
    Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF. Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley survey. BMJ 1989; 298: 920–4.Google Scholar
  14. 14.
    Knekt P, Reunanen A, Aromaa A, Heliovaara M, Hakulinen T, Hakama M. Serum cholesterol and risk of cancer in a cohort of 39,000 men and women. J Clin Epidemiol 1988; 41: 519–30.Google Scholar
  15. 15.
    Schatzkin A, Hoover RN, Taylor PR, et al. Serum cholesterol and cancer in the NHANES 1 epidemiologic follow-up study. Lancet 1987; ii: 298–301.Google Scholar
  16. 16.
    Wald NJ, Thompson SG, Law MR, Densem JW, Bailey A. Serum cholesterol and subsequent risk of cancer: results from the BUPA study. Br J Cancer 1989; 59: 936–8.Google Scholar
  17. 17.
    Wingard DL, Criqui MH, Holdbrook MJ, Barrett-Connor E. Plasma cholesterol and cancer morbidity and mortality in an adult community. J Chronic Dis 1984; 37: 401–6.Google Scholar
  18. 18.
    Sorlie PD, Feinleib M. The serum cholesterol-cancer relationship: an analysis of time trends in the Framingham Study. JNCI 1982; 69: 989–96.Google Scholar
  19. 19.
    Morris DL, Borhani NO, Fitzsimons E, et al. Serum cholesterol and cancer in the Hypertension Detection and Follow-up Program. Cancer 1983; 52: 1754–9.Google Scholar
  20. 20.
    Wallace RB, Rost C, Burmeister LF, Pomrehn PR. Cancer incidence in humans: relationship to plasma lipids and relative weight. JNCI 1982; 68: 915–8.Google Scholar
  21. 21.
    Thomas CB, Duszynski KR, Shaffer JW. Cholesterol levels in young adulthood and subsequent cancer: a preliminary note. Johns Hopkins Med J 1982; 150: 89–94.Google Scholar
  22. 22.
    Cowan LD, O'Connell DL, Criqui MH, Barrett-Connor E, Bush TL, Wallace RB. Cancer mortality and lipid and lipoprotein levels. Am J Epidemiol 1990; 131: 468–82.Google Scholar
  23. 23.
    Kozarevic DJ, McGee D, Vojvodic N, et al. Serum cholesterol and mortality: The Yugoslavia Cardiovascular Disease Study. Am J Epidemiol 1981; 114: 21–8.Google Scholar
  24. 24.
    Westlund K, Nicholaysen R. Ten-year mortality and morbidity related to serum cholesterol. Scand J Clin Lab Invest 1972; 30 (suppl 127): 3–24.Google Scholar
  25. 25.
    Salonen JT. Risk of cancer and death in relation to serum cholesterol: a longitudinal study in an Eastern Finnish population with high overall cholesterol level. Am J Epidemiol 1982; 116: 622–30.Google Scholar
  26. 26.
    Böttiger LE, Carlson LA. Risk factors for death for males and females: a study of the death pattern in the Stockholm Prospective Study. Acta Med Scand 1982; 221: 437–42.Google Scholar
  27. 27.
    Gerhardsson M, Rosengvist U, Ahlbom A, Carlson LA. Serum cholesterol and cancer—a retrospective case-control study. Int J Epidemiol 1986; 15: 155–9.Google Scholar
  28. 28.
    Peterson B, Trell E. Premature mortality in middle-aged men: serum cholesterol as risk factor. Klin Wochenschr 1983; 63: 795–801.Google Scholar
  29. 29.
    Rose G, Blackburn H, Keys A, et al. Colon cancer and blood cholesterol. Lancet 1974; i: 181–3.Google Scholar
  30. 30.
    Rose G, Shipley MJ. Plasma lipids and mortality: A source of error. Lancet 1980; i: 523–6.Google Scholar
  31. 31.
    Cambien F, Ducimetiere P, Richard J. Total serum cholesterol and cancer mortality in a middle-aged male population. Am J Epidemiol 1980; 112: 388–94.Google Scholar
  32. 32.
    Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987; 9: 1–30.Google Scholar
  33. 33.
    Armitage P, Berry G. Statistical Methods in Medical Research. Oxford, England: Blackwell Scientific Publications, 1987: 194–5.Google Scholar
  34. 34.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin Trials 1986; 7: 177–88.Google Scholar
  35. 35.
    Tornberg SA, Holm LE, Cartensen JM, Eklund GA Odont D. Risks of cancer of the colon and rectum in relation to serum cholesterol and beta-lipoprotein. N Engl J Med 1986; 315: 1629–33.Google Scholar
  36. 36.
    Schatzkin A, Hoover RN, Taylor PR, et al. Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Cancer Res 1988; 48: 452–8.Google Scholar
  37. 37.
    Stemmerman GN, Nomura AMY, Heilbrun LK, Pollack ES, Kagan A. Serum cholesterol and colon cancer incidence in Hawaiian Japanese men. JNCI 1981; 67: 1179–82.Google Scholar
  38. 38.
    Winawer SJ, Flehinger BJ, Buchalter J, Herbert E, Shike M. Declining serum cholesterol levels prior to diagnosis of colon cancer: a time-trend, case-control study. JAMA 1990; 263: 2083–5.Google Scholar
  39. 39.
    Neugut AI, Johnsen CM, Fink DJ. Serum cholesterol levels in adenomatous polyps and cancer of the colon. JAMA 186; 255: 365–7.Google Scholar
  40. 40.
    Miller SR, Tartter PI, Papatestas AE, Slater G, Aufses AH. Serum cholesterol and human colon cancer. JNCI 1981: 67: 297–300.Google Scholar
  41. 41.
    Abeatici S, Castagno PL, Palestini N, Nieddu L. La colesterolemia nei soggetti affetti da neoplasia. Minerva Med 1989; 80: 1085–90.Google Scholar
  42. 42.
    Gilbert HS, Ginsberg H, Fagerstrom R, Brown WV. Characterization of hypocholesterolemia in myeloproliferative disease. Am J Med 1981; 71: 595–602.Google Scholar
  43. 43.
    Budd D, Ginsberg H. Hypocholesterolemia and acute myelogenous leukaemia. Cancer 1986; 58: 1361–5.Google Scholar
  44. 44.
    Venkatanarayanan S, Nagarajan B. Association between tumour status and serum lipoprotein cholesterol in hemopoietic malignancy. Biochem Int 1988; 17: 499–507.Google Scholar
  45. 45.
    Törnberg SA, Holm LE, Carstensen JM. Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressure. Acta Oncol 1988; 27: 31–7.Google Scholar
  46. 46.
    Vatten LJ, Foss OP. Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women. Cancer Res 1990; 50: 2341–6.Google Scholar
  47. 47.
    Abramson ZH, Kark JD. Serum cholesterol and primary brain tumours: A case-control study. Br J Cancer 1985; 52: 93–8.Google Scholar
  48. 48.
    Davey Smith G, Shipley MJ. Plasma cholesterol concentration and primary brain tumours. Br Med J 1989; 299: 26–7.Google Scholar
  49. 49.
    Neuget AI, Fink DJ, Radin D. Serum cholesterol and primary brain tumours: A case-control study. Int J Epidemiol 1989; 18: 798–801.Google Scholar
  50. 50.
    Knekt P, Reunanen A, Teppo L. Serum cholesterol concentration and risk of primary brain tumours. Br Med J 1991; 302: 90.Google Scholar
  51. 51.
    Vitols S, Gahrton G, Bjorkholm M, Peterson C. Hypocholesterolaemia in malignancy due to elevated lowdensity-lipoprotein-receptor activity in tumour cells: evidence from studies in patients with leukaemia. Lancet 1985; 2: 1150–4.Google Scholar
  52. 52.
    Henrlksson 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.Google Scholar
  53. 53.
    Reverter JC, Sierra J, Marti-Tutusaus JM, Montserrat E, Granena A, Rozman C. Hypocholesterolemia in acute myelogenous leukemia. Eur J Haematol 1988; 41: 317–20.Google Scholar
  54. 54.
    Peto R, Boreham J, Chen J, Li J, Campbell TC, Brun T. Plasma cholesterol, coronary heart disease, and cancer. BMJ 1989; 298: 1249.Google Scholar
  55. 55.
    Wynder EL, Hebert JR, Kabat GC. Association of dietary fat and lung cancer. JNCI 1987; 79: 631–7.Google Scholar
  56. 56.
    Goodman MT, Kolonel LN, Yoshizawa CN, Hankin JH. The effect of dietary cholesterol and fat on the risk of lung cancer in Hawaii. Am J Epidemiol 1988; 128: 1241–55.Google Scholar
  57. 57.
    Freedman DS, Srinivasan SR, Shear CL, et al. Cigarette smoking initiation and longitudinal changes in serum lipids and lipoproteins in early adulthood: the Bogalusa Heart Study. Am J Epidemiol 1986; 124: 207–19.Google Scholar
  58. 58.
    Dwyer JH, Rieger-Ndakorerwa GE, Semmer NK, Fuchs R, Lippert P. Low-level cigarette smoking and longitudinal change in serum cholesterol among adolescents. JAMA 1988; 259: 2857–62.Google Scholar
  59. 59.
    Stubbe I, Eskilsson J, Nilsson-Ehle P. High-density lipoprotein concentrations increase after stopping smoking. Br Med J 1982; 284: 1511–3.Google Scholar
  60. 60.
    de Parscau L, Fielding CJ. Abnormal plasma cholesterol metabolism in cigarette smokers. Metabolism 1986; 35: 1070–3.Google Scholar
  61. 61.
    Rigotti NA. Cigarette smoking and body weight. N Engl J Med 1989; 320: 931–3.Google Scholar
  62. 62.
    Williamson DF, Madans J, Anda RF, Kleinman JC, Giovino GA, Byers T. Smoking cessation and severity of weight gain in a national cohort. N Engl J Med 1991; 324: 739–45.Google Scholar
  63. 63.
    Marti B, Tuomilehto J, Korhonen HJ, et al. Smoking and leanness: evidence for change in Finland. Br Med J 1989; 298: 1287–90.Google Scholar
  64. 64.
    Whichelow MJ, Golding JF, Treasure FP. Comparison of some dietary habits of smokers and non-smokers. Br J Addict 1988; 83: 295–304.Google Scholar
  65. 65.
    Cade J, Margetts B. Cigarette smoking and serum lipid and lipoprotein concentrations. Br Med J 1989; 298: 1312.Google Scholar
  66. 66.
    Fulton M, Thomson M, Elton RA, Brown S, Wood DA, Oliver MF. Cigarette smoking, social class and nutrient intake: relevance to coronary heart disease. Eur J Clin Nutr 1988; 42: 797–803.Google Scholar
  67. 67.
    Craig WY, Palomaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. Br Med J 1989; 298: 784–8.Google Scholar
  68. 68.
    Mjos OD. Lipid effects of smoking. Am Heart J 1988; 115: 272–5.Google Scholar
  69. 69.
    Stuart A, Ord JK. Kendall's Advanced Theory of Statistics, 5th Edition, Vol 1. London: Griffin, 1987: 330–1.Google Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1991

Authors and Affiliations

  • M. R. Law
  • S. G. Thompson

There are no affiliations available

Personalised recommendations