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Myeloma risk factors

The key risk factors for myeloma (sometimes called multiple myeloma) are discussed on this page. Myeloma risk is also strongly linked with age, sex and ethnicity

Overall, the evidence on myeloma risk factors is limited, mainly because of the relative rarity of this cancer type.1

Meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and most take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.

Myeloma risk factors overview

The International Agency for Research on Cancer (IARC) evaluates evidence on the carcinogenic risk to humans of a number of exposures including tobacco, alcohol, infections, radiation, occupational exposures, and medications.10,32 The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) evaluates evidence for other exposures including diet, overweight and obesity, and physical exercise.33 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. IARC's conclusions about myeloma risk factors are shown in Table 4.1. The WCRF/AICR evaluation does not include myeloma because the evidence is very limited.

Table 4.1: IARC Evaluation of Myeloma Risk Factors

Increases risk ('sufficient' or 'convincing' evidence) May increase risk ('limited' or 'probable' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)
-
  • Benzene
  • Ethylene oxide
  • X-radiation, gamma radiation
- -

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Family history and genetic conditions

Family history

Myeloma or MGUS (monoclonal gammopathy of undetermined significance) risk is 2-3 times higher in people with a first-degree relative (parent, sibling or child) with myeloma or MGUS, versus people without such family history, case-control studies have shown.2

This may be due to shared genetic or environmental factors, or a combination of these.

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Genetic conditions

Myeloma risk is higher in people with Gaucher syndrome, a systematic review showed.37

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Immune system

Autoimmune conditions

Myeloma risk is 47-50% higher in people with pernicious anaemia, compared with those without the disease, meta-analyses have shown.6,35 MGUS risk is 67% higher in people with pernicious anaemia.6

Myeloma risk is almost 3 times higher in people with autoimmune haemolytic anaemia, and 77% higher in those with ankylosing spondylitis,35 meta-analyses have shown. Myeloma risk is 11% lower in those with psoriasis, a meta-analysis showed.6 

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Organ transplant

Myeloma risk may be tripled in solid organ transplant recipients, a meta-analysis showed.5 However US data indicate that myeloma risk is only around 40% higher in transplant recipients versus the general population,9 and that overall, post-transplant myeloma develops in less than 1% of organ recipients.4

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Infections

Human immunodeficiency virus (HIV)

Myeloma risk is 2.6 times higher in people with HIV/AIDS, compared with the general population, a meta-analysis showed.11 

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Medical conditions and treatments

Pneumonia

Myeloma risk is higher in people with previous pneumonia, some cohort studies have shown.8,34 However, this may reflect increased pneumonia risk in people with undetected myeloma (rather than pneumonia causing myeloma); the association may only be found quite soon after pneumonia diagnosis.12

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Overweight and obesity

Myeloma risk is 11-14% higher per 5-unit body mass index (BMI) increment, meta-analyses have shown.13-15

Obese people may produce more of the protein interleukin-6 (IL-6), affecting proliferation and development of normal and malignant plasma cells.13

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Ionising radiation

X radiation and gamma radiation are classified by IARC as probable causes of myeloma, based on limited evidence (Table 4.1).10 However, the evidence is not strong.18

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Occupational exposures

Benzene and ethylene oxide are classified by IARC as probable causes of myeloma, based on limited evidence (Table 4.1).10

Myeloma risk is doubled in people with occupational exposure to methylene chloride, compared with unexposed people, a meta-analysis showed.36 Myeloma risk is not associated with benzene or trichloroethylene exposure, meta-analyses have shown.19-22,30

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Factors shown to have no effect on myeloma risk

Myeloma risk is not associated with the following factors, meta- and pooled analyses or systematic reviews have shown:

  • Tobacco smoking.29
  • Alcohol31 (though some evidence of risk decreaase at high intake levels31,40).
  • Physical activity.16
  • Rheumatoid arthritis.35
  • Diabetes.39
  • Pesticide/herbicide exposure.23,24,38
  • Diet.1
  • Working with livestock.25
  • Working in the meat industry.26
  • Working as a metal processor, cleaner, or with high exposure to organic solvents.38
  • Hair dyes.27,28

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section updated 29/08/14

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References for myeloma risk factors

  1. Alexander DD, Mink PJ, Adami HO, et al. Multiple myeloma: a review of the epidemiologic literature. Int J Cancer 2007;120 Suppl 12:40-61.
  2. Kristinsson SY, Goldin LR, Bjorkholm M, et al. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica 2009;94(11):1581-9.
  3. Parker A, Bowles K, Bradley JA, et al. Brit J Haematol 2010;149(5):675-92.
  4. Caillard S, Agodoa LY, Bohen EM, et al. Myeloma, Hodgkin disease, and lymphoid leukemia after renal transplantation: characteristics, risk factors and prognosis. Transplantation 2006;81(6):888-95.
  5. Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007;370(9581):59-67.
  6. McShane CM, Murray LJ, Landgren O, et al. Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: a systematic review. Cancer Epidemiol Biomarkers Prev. 2014 Feb;23(2):332-42.
  7. Goldin LR, Landgren O. Autoimmunity and lymphomagenesis. Int J Cancer 2009;124(7):1497-502.
  8. Brown LM, Gridley G, Check D, et al. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood 2008;111(7):3388-94.
  9. Engels EA, Clarke CA, Pfeiffer RM, et al. Plasma cell neoplasms in US solid organ transplant recipients. Am J Transplant. 2013;13(6):1523-32.
  10. Cogliano VJ, Baan R, Straif K, et al. Preventable Exposures Associated With Human Cancers. Journal of the National Cancer Institute 2011;103(24):1827-39.
  11. Shiels MS, Cole SR, Kirk GD, et al. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acq Immun Def Synd 2009;52(5):611-22.
  12. Landgren O, Rapkin JS, Mellemkjaer L, et al. Respiratory tract infections in the pathway to multiple myeloma: a population-based study in Scandinavia. Haematologica 2006;91(12):1697-700
  13. Larsson SC, Wolk A. Body mass index and risk of multiple myeloma: A meta-analysis. Int J Cancer 2007.
  14. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371(9612):569-78.
  15. Wallin A, Larsson SC. Body mass index and risk of multiple myeloma: a meta-analysis of prospective studies. Eur J Cancer. 2011;47(11):1606-15.
  16. Jochem C, Leitzmann MF, Keimling M, et al. Physical activity in relation to risk of hematologic cancers: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(5):833-46.
  17. Parkin DM, Boyd L. 8. Cancers attributable to overweight and obesity in the UK in 2010. Br J Cancer 2011;105(S2):S34-S37.
  18. United Nations Scientific Committee on the Effects of Atomic Radiation 2009. UNSCEAR 2006 Report to the General Assembly, with scientific annexes. Annex A.
  19. Galbraith D, Gross SA, Paustenbach D. Benzene and human health: A historical review and appraisal of associations with various diseases. Crit Rev Toxicol 2010;40 Suppl 2:1-46.
  20. Bergsagel DE, Wong O, Bergsagel PL, et al. Benzene and multiple myeloma: appraisal of the scientific evidence. Blood 1999;94(4):1174-82.
  21. Sonoda T, Nagata Y, Mori M, et al. Meta-analysis of multiple myeloma and benzene exposure. J Epidemiol 2001;11(6):249-54.
  22. Alexander DD, Mink PJ, Mandel JH, et al. A meta-analysis of occupational trichloroethylene exposure and multiple myeloma or leukaemia. Occup Med - C 2006;56(7):485-93.
  23. Jones DR, Sutton AJ, Abrams KR, et al. Systematic review and meta-analysis of mortality in crop protection product manufacturing workers. Occup Environ Med 2009;66(1):7-15.
  24. Merhi M, Raynal H, Cahuzac E, et al. Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies. Cancer Cause Control 2007;18(10):1209-26.
  25. Perrotta C, Staines A, Cocco P. Multiple myeloma and farming. A systematic review of 30 years of research. Where next? J Occup Med Toxicol 2008;3:27.
  26. Moore T, Brennan P, Becker N, et al. Occupational exposure to meat and risk of lymphoma: a multicenter case-control study from Europe. Int J Cancer 2007;121(12):2761-6.
  27. Takkouche B, Regueira-Mendez C, Montes-Martinez A. Risk of cancer among hairdressers and related workers: a meta-analysis. Int J Epidemiol 2009;38(6):1512-31.
  28. Rollison DE, Helzlsouer KJ, Pinney SM. Personal hair dye use and cancer: a systematic literature review and evaluation of exposure assessment in studies published since 1992. J Toxicol Env Heal B 2006;9(5):413-39.
  29. Psaltopoulou T, Sergentanis TN, Kanellias N, et al. Tobacco smoking and risk of multiple myeloma: a meta-analysis of 40 observational studies. Int J Cancer. 2013 May 15;132(10):2413-31.
  30. Karami S, Bassig B, Stewart PA, et al. Occupational trichloroethylene exposure and risk of lymphatic and haematopoietic cancers: a meta-analysis. Occup Environ Med. 2013 Aug;70(8):591-9.
  31. Rota M, Porta L, Pelucchi C, et al. Alcohol drinking and multiple myeloma risk--a systematic review and meta-analysis of the dose-risk relationship. Eur J Cancer Prev. 2014 Mar;23(2):113-21.
  32. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 105*. Available from http://monographs.iarc.fr/ENG/Classification/index.php. Accessed May 2014.
  33. 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.
  34. Søgaard KK, Farkas DK, Pedersen L, et al. Pneumonia and the incidence of cancer: a Danish nationwide cohort study. J Intern Med. 2014.
  35. Shen K, Xu G, Wu Q, et al. Risk of multiple myeloma in rheumatoid arthritis: a meta-analysis of case-control and cohort studies. PLoS One. 2014;9(3):e91461
  36. Liu T, Xu QE, Zhang CH, et al. Occupational exposure to methylene chloride and risk of cancer: a meta-analysis. Cancer Causes Control. 2013;24(12):2037-49.
  37. Arends M, van Dussen L, Biegstraaten M, et al. Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature. Br J Haematol. 2013;161(6):832-42.
  38. Perrotta C, Kleefeld S, Staines A, et al. Multiple myeloma and occupation: a pooled analysis by the International Multiple Myeloma Consortium. Cancer Epidemiol. 2013;37(3):300-5.
  39. Castillo JJ, Mull N, Reagan JL, et al. Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies. Blood. 2012;119(21):4845-50.
  40. Ji J, Sundquist J, Sundquist K. Alcohol consumption has a protective effect against hematological malignancies: a population-based study in sweden including 420,489 individuals with alcohol use disorders. Neoplasia 2014;16(3):229-34.
Updated: 18 June 2014