Hodgkin lymphoma risk factors

45% of Hodgkin lymphoma cases each year in the UK are linked to major lifestyle and other risk factors.[1]

Hodgkin lymphoma risk is associated with a number of risk factors.

Hodgkin Lymphoma 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)
  • Epstein-Barr virus
  • HIV

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International Agency for Research on Cancer (IARC) classification. World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classification does not include testicular cancer because the evidence is very limited

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Epstein-Barr virus (EBV) infection is classified by the International Agency for Research on Cancer (IARC) as a cause of Hodgkin lymphoma.[1,2] 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).[3]

Infectious mononucleosis (IM, commonly known as glandular fever) is a common manifestation of EBV infection.[4] Hodgkin lymphoma risk is 2.6-6 times higher in people with a history of IM, cohort studies have shown.[4-6] 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.[4,7]

References

  1. 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.
  2. Cogliano VJ, Baan R, Straif K, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst 2011; 103:1827-39.
  3. Parkin DM. Cancers attributable to infection in the UK in 2010. Br J Cancer 2011; 105(S2):S49-S56.
  4. Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 2003;349(14):1324-32.
  5. Goldacre MJ, Wotton CJ, Yeates DG. Associations between infectious mononucleosis and cancer: record-linkage studies. Epidemiol Infect 2009;137(5):672-80.
  6. Hjalgrim H, Askling J, Sørensen P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92(18):1522-8
  7. Hjalgrim H, Smedby KE, Rostgaard K, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res 2007;67(5):2382-8.
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Human immunodeficiency virus (HIV) infection is classified by the International Agency for Research on Cancer (IARC) as a cause of Hodgkin lymphoma.[1,2]

Hodgkin lymphoma risk is 11 times higher in people with HIV compared with the general population, meta-analyses have shown.[3,4]

Among people with HIV, Hodgkin lymphoma risk is nearly 3 times higher in those with AIDS versus those without.[3] Hodgkin lymphoma in HIV may be part of an immune reconstitution syndrome, whereby risk is higher in those who have enough functioning immune cells to ‘recruit’ to Hodgkin lymphoma development, but not enough to halt that development.[5]

The association with HIV may partly reflect increased Epstein-Barr virus (EBV) incidence in the HIV-infected population, though HIV/AIDS-related decreased immune function is thought to also impact Hodgkin lymphoma risk independently.[3]

References

  1. 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.
  2. Cogliano VJ, Baan R, Straif K, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst 2011; 103:1827-39.
  3. Shiels MS, Cole SR, Kirk GD, et al. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr 2009;52(5):611-22.
  4. 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.
  5. Carbone A, Vaccher E, Gloghini A, et al. Diagnosis and management of lymphomas and other cancers in HIV-infected patients.. Nat Rev Clin Oncol 2014;11(4):223-38.
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Hodgkin lymphoma risk is 28% lower in teenagers and young adults with 3 or more siblings, compared with only-children, a cohort study showed.[1] This may indicate that Hodgkin lymphoma risk is reduced by exposure to common childhood infections.

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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.[1-4] Transplant patients receive immunosuppressant medication, increasing their risk of Epstein-Barr virus (EBV) infection; this is thought to the be the mechanism behind their increased Hodgkin lymphoma risk.[2]

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Hodgkin lymphoma risk is increased in a number of autoimmune conditions, compared with the general population: rheumatoid athritis (2-3 times higher),[1-3] systemic lupus erythematosus (3-8 times),[4,5] Sjögren’s syndrome (4-5 times),[2,3] sarcoidosis (4-10 times),[2,3] psoriasis (2 times),[3] and coeliac disease (around doubled risk of Hodgkin lymphoma death).[6] Associations with systemic autoimmune disease may be limited to classical Hodgkin lymphoma.[2,3] Hodgkin lymphoma risk may also be slightly increased in people with a family history of sarcoidosis,[7] and in children with a family history of autoimmune disease or allergy.[8]

References

  1. Smitten AL, Simon TA, Hochberg MC, et al. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 2008;10(2):R45.
  2. Kristinsson SY, Landgren O, Sjöberg J, et al. Autoimmunity and risk for Hodgkin's lymphoma by subtype. Haematologica 2009;94(10):1468-9.
  3. Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K. Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. Ann Oncol. 2014;25(7):1397-404.
  4. Bernatsky S, Ramsey-Goldman R, Isenberg D, et al. Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford) 2007;46(5):830-2.
  5. Apor E, O'Brien J, Stephen M, Castillo JJ. Systemic lupus erythematosus is associated with increased incidence of hematologic malignancies: a meta-analysis of prospective cohort studies. Leuk Res 2014;38(9):1067-71.
  6. Tio M, Cox MR, Eslick GD. Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther 2012;35(5):540-51.
  7. Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst 2006; 98(18):1321-30.
  8. Linabery AM, Erhardt EB, Fonstad RK, et al. Infectious, autoimmune and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children's Oncology Group study. Int J Cancer. 2014 Feb 13.
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Hodgkin lymphoma risk is 7 times higher in survivors of non-Hodgkin lymphoma, compared with the general population, a meta-analysis showed.[1] Hodgkin lymphoma risk is not increased among survivors of childhood cancer, a cohort study showed.[2]

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Hodgkin lymphoma risk is around 3 times higher in first-degree relatives Open a glossary item of Hodgkin lymphoma patients, a pooled analysis showed.[1] Risk is higher when the affected relative is younger, and is higher in siblings of affected relatives (rather than parents), particularly males.[1]

Hodgkin lymphoma risk is not increased with family history of most other haemotological cancers or related disorders,[2] though it may be around doubled in first-degree relatives of diffuse large B-cell lymphoma patients.[3]

References

  1. Goldin LR, Pfeiffer RM, Gridley G, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 2004; 100(9):1902-8.
  2. 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.
  3. 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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Hodgkin lymphoma risk is 41% higher in obese people (body mass index Open a glossary item [BMI] 30+) compared with those of a healthy weight, a meta-analysis showed, though risk does not appear to increase linearly with BMI.[1] The association may vary by sex and age, a case-control study indicates.[2]

Hodgkin lymphoma risk is not associated with birth weight, a meta-analysis showed.[3]

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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.[1] The trend for increased risk with increasing height was weaker in a UK cohort study of older women.[2]

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Hodgkin lymphoma risk is 10-15% higher in ever-smokers, compared with never-smokers, meta- and pooled-analyses have shown.[1-3] The association may be limited to current smokers,[2,3] with a dose-response effect.[1,3] It may be limited to, or stronger in, men and older patients.[2,3] Among current smokers the association may be limited to mixed cellularity and Epstein-Barr virus (EBV)-positive classical subtypes.[2]

Childhood Hodgkin lymphoma risk is not associated with maternal smoking during pregnancy, a meta-analysis showed.[4]

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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.[1] Hodgkin lymphoma risk is lower in people with alcohol use disorders, a cohort study showed.[2]

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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 Epstein-Barr virus (EBV)-positive tumours.[1] Excessive UV exposure increases the risk of skin cancer.

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

  • Being breastfed (childhood Hodgkin lymphoma).[1]
  • Working as a professional hairdresser.[2]
  • Personal hair dye use.[3]
  • Trichloroethylene (occupational exposure).[4]
  • Benzene (occupational exposure).[5]
  • Pentachlorophenol (PCP; occupational exposure).[6]
  • Working in pesticide production.[7]
  • Physical activity.[8,9]
  • Aspirin (though some evidence of risk decrease with longer duration of use).[10]
  • Hepatitis C infection.[11]
  • Measles infection.[12]
  • Asthma.[13]

References

  1. Wang KL, Liu CL, Zhuang Y, et al. Breastfeeding and the risk of childhood Hodgkin lymphoma: a systematic review and meta-analysis. Asian Pac J Cancer Prev 2013;14(8):4733-7.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Zheng R, Zhang Q, Zhang Q, et al. Occupational exposure to pentachlorophenol causing lymphoma and hematopoietic malignancy for two generations. Toxicol Ind Health 2013.
  7. 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.
  8. Vermaete NV, Wolter P, Verhoef GE, et al. Physical activity and risk of lymphoma: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2013;22(7):1173-84.
  9. Jochem C, Leitzmann MF, Keimling M, Schmid D, Behrens G. Physical activity in relation to risk of hematologic cancers: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2014;23(5):833-46.
  10. Chang ET, Frøslev T, Sørensen HT, et al. A nationwide study of aspirin, other non-steroidal anti-inflammatory drugs, and Hodgkin lymphoma risk in Denmark. Br J Cancer 2011;105(11):1776-82.
  11. 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.
  12. Wilson KS, Freeland JM, Gallagher A, et al. Measles virus and classical Hodgkin lymphoma: no evidence for a direct association. Int J Cancer 2007;121(2):442-7.
  13. Dikalioti SK, Chang ET, Dessypris N, et al. Allergy-associated symptoms in relation to childhood non-Hodgkin's as contrasted to Hodgkin's lymphomas: a case-control study in Greece and meta-analysis. Eur J Cancer 2012;48(12):1860-6.
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