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Hodgkin lymphoma risk factors

The key risk factors for Hodgkin lymphoma are discussed on this page. Hodgkin lymphoma risk is also linked with age and sex

Overall, the evidence on Hodgkin lymphoma risk factors is limited, mainly because of this cancer's relative rarity and diversity. Studies which group together different morphological subtypes of Hodgkin lymphoma may be confounded if those subtypes have differing aetiologies.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. 

Hodgkin lymphoma 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.2,3 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.4 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. The WCRF/AICR evaluation does not include Hodgkin lymphoma because the evidence is very limited. IARC's conclusions about Hodgkin lymphoma risk factors are shown in Table 4.1.

Table 4.1: IARC Evaluation of Hodgkin Lymphoma Risk Factors

Increases risk ('sufficient' or 'convincing' evidence)2,3 May increase risk ('limited' or 'probable' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)
  • Epstein-Barr virus
  • HIV

-

-

-

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Age and sex

Hodgkin lymphoma is more common in males than females, and shows a clear bimodal age distribution, with the first peak in incidence rates in young adults, and the second peak in older men and women. 

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Infections

Epstein-Barr Virus (EBV)

Epstein-Barr virus (EBV) infection is classified by IARC as a cause of Hodgkin lymphoma (Table 4.1).2,3 An estimated 45% of Hodgkin lymphoma cases in the UK are linked to EBV infection (though this varies by age, with a higher proportion in children and older adults, and a lower proportion in younger adults).5

Infectious mononucleosis (IM, commonly known as glandular fever) is a common manifestation of EBV infection.6 Hodgkin lymphoma risk is 2.6-6 times higher in people with a history of IM, cohort studies have shown.6-8 The association appears to be limited to EBV-positive Hodgkin lymphoma, and Hodgkin lymphoma is diagnosed on average 3-4 years after IM, Nordic studies show.6,9

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Human Immunodeficiency Virus (HIV)

Human immunodeficiency virus (HIV) infection is classified by IARC as a cause of Hodgkin lymphoma (Table 4.1).2,3 Hodgkin lymphoma risk is 11 times higher in people with HIV compared with the general population, meta-analyses have shown.10,11 Among people with HIV, Hodgkin lymphoma risk is nearly 3 times higher in those with AIDS versus those without.10 This may partly reflect increased EBV incidence in the HIV-infected population, though HIV/AIDS-related decreased immune function is thought to also impact Hodgkin lymphoma risk independently.10

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Other infections

Hodgkin lymphoma risk is 28% lower in teenagers and young adults with 3 or more siblings, compared with only-children, a cohort study showed.51 This may indicate that Hodgkin lymphoma risk is reduced by exposure to common childhood infections.

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Immune system

Organ transplant

Hodgkin lymphoma risk is around 2-4 times higher in recipients of solid organ transplants compared with the general population, a meta-analysis and several cohort studies have shown.11-14 Transplant patients receive immunosuppressant medication, increasing their risk of EBV infection; this is thought to the be the mechanism behind their increased Hodgkin lymphoma risk.12

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Autoimmune conditions

Hodgkin lymphoma risk is increased in a number of autoimmune conditions, compared with the general population: rheumatoid athritis (2-3 times higher),15,16,50 systemic lupus erythematosus (3-8 times),16,17,50 Sjögren’s syndrome (4-5 times),16,50 sarcoidosis (4-10 times),16, 50 psoriasis (2 times),50 and coeliac disease (around doubled risk of Hodgkin lymphoma death).18 Associations with systemic autoimmune disease may be limited to classical Hodgkin lymphoma.16,50 Hodgkin lymphoma risk may also be slightly increased in people with a family history of sarcoidosis,19 and in children with a family history of autoimmune disease or allergy.48

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Previous cancer

Hodgkin lymphoma risk is 7 times higher in survivors of non-Hodgkin lymphoma, compared with the general population, a meta-analysis showed.20 Hodgkin lymphoma risk is not increased among survivors of childhood cancer, a cohort study showed.21

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Family history

Hodgkin lymphoma risk is around 3 times higher in first-degree relatives of Hodgkin lymphoma patients, a pooled analysis showed.22 Risk is higher when the affected relative is younger, and is higher in siblings of affected relatives (rather than parents), particularly males.22

Hodgkin lymphoma risk is not increased with family history of most other haemotological cancers or related disorders,23 though it may be around doubled in first-degree relatives of diffuse large B-cell lymphoma patients.24

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Overweight and obesity

Hodgkin lymphoma risk is 41% higher in obese people (body mass index [BMI] 30+) compared with those of a healthy weight, a meta-analysis showed, though risk does not appear to increase linearly with BMI.25 The association may vary by sex and age, a case-control study indicates.26

Hodgkin lymphoma risk is not associated with birth weight, a meta-analysis showed.27

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Height

Hodgkin lymphoma risk may be slightly increased in taller people (in men, 22% higher for 180cm+ versus 170-179cm; in women, 53% higher for 170cm+ versus 160-196cm), a Nordic cohort study showed.28 The trend for increased risk with increasing height was weaker in a UK cohort study of older women.29

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Tobacco

Hodgkin lymphoma risk is 10-15% higher in ever-smokers, compared with never-smokers, meta- and pooled-analyses have shown.30-32 The association may be limited to current smokers,31,32 with a dose-response effect.30,32 It may be limited to, or stronger in, men and older patients.31,32 Among current smokers the association may be limited to mixed cellularity and EBV-positive classical subtypes.31

Childhood Hodgkin lymphoma risk is not associated with maternal smoking during pregnancy, a meta-analysis showed.33

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Factors shown to decrease or have no effect on Hodgkin lymphoma risk

Decrease

Alcohol consumption may reduce risk of Hodgkin lymphoma, a meta-analysis showed, though there was no dose- response effect, and the association was largely limited to case-control studies, calling into question the mechanism and validity of the association.34 Hodgkin lymphoma risk is lower in people with alcohol use disorders, a cohort study showed.52

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Hodgkin lymphoma risk appears to be decreased at higher levels of ultraviolet (UV) radiation exposure, a pooled analysis showed, though dose-response effects were inconsistent and any association may be limited to EBV-positive tumours.35 Excessive UV exposure increases the risk of skin cancer.

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No effect

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

  • Being breastfed (childhood Hodgkin lymphoma).36
  • Working as a professional hairdresser.37 
  • Personal hair dye use.38
  • Trichloroethylene (occupational exposure).39
  • Benzene (occupational exposure).40
  • Pentachlorophenol (PCP; occupational exposure).41
  • Working in pesticide production.42
  • Physical activity.43,49
  • Aspirin (though some evidence of risk decrease with longer duration of use).44 
  • Hepatitis C infection.45
  • Measles infection.46
  • Asthma.47

section reviewed 19/03/14
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References for Hodgkin's lymphoma risk factors

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  2. 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 October 2013.
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  4. 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.
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  7. Goldacre MJ, Wotton CJ, Yeates DG. Associations between infectious mononucleosis and cancer: record-linkage studies. Epidemiol Infect 2009;137(5):672-80.
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  21. Friedman DL, Whitton J, Leisenring W, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 2010;102(14):1083-95.
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  23. Kristinsson SY, Goldin LR, Björkholm M, et al. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica 2009;94(11):1581-9.
  24. Goldin LR, Björkholm M, Kristinsson SY, et al. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol 2009;146(1):91-4.
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  29. Murphy F, Kroll ME, Pirie K, et al. Body size in relation to incidence of subtypes of haematological malignancy in the prospective Million Women Study. Br J Cancer 2013;108(11):2390-8.
  30. Sergentanis TN, Kanavidis P, Michelakos T, et al. Cigarette smoking and risk of lymphoma in adults: a comprehensive meta-analysis on Hodgkin and non-Hodgkin disease. Eur J Cancer Prev 2013;22(2):131-50.
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  37. Takkouche B, Regueira-Méndez C, Montes-Martínez A. Risk of cancer among hairdressers and related workers: a meta-analysis. Int J Epidemiol 2009;38(6):1512-31.
  38. Takkouche B, Etminan M, Montes-Martínez A. Personal use of hair dyes and risk of cancer: a meta-analysis. JAMA.2005;293(20):2516-25.
  39. 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;70(8):591-9.
  40. Vlaanderen J, Lan Q, Kromhout H, et al. Occupational benzene exposure and the risk of lymphoma subtypes: a meta-analysis of cohort studies incorporating three study quality dimensions. Environ Health Perspect 2011;119(2):159-67.
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  45. Dal Maso L, Franceschi S. Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies. Cancer Epidemiol Biomarkers Prev 2006;15(11):2078-85.
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Updated: 1 May 2014