ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Hodgkin lymphoma: Epidemiology and risk factors

Hodgkin lymphoma: Epidemiology and risk factors
Literature review current through: Jan 2024.
This topic last updated: Jan 31, 2022.

INTRODUCTION — Hodgkin lymphomas (HL; formerly called Hodgkin's disease) are lymphoid neoplasms in which the malignant cells are admixed with a heterogeneous population of non-neoplastic inflammatory cells.

HL is divided into two major subgroups, based on morphology and immunophenotype [1] (table 1):

Classic HL (cHL), which is further categorized according to histology:

Nodular sclerosis cHL (NSCHL)

Mixed cellularity cHL (MCCHL)

Lymphocyte rich cHL (LRCHL)

Lymphocyte depleted cHL (LDCHL)

Nodular lymphocyte predominant HL (NLPHL)

This topic will review the epidemiology and risk factors for cHL and NLPHL.

Clinical presentation and diagnosis, and pretreatment evaluation, staging, and prognosis of cHL are discussed separately.

(See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

(See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)

Clinical manifestations, diagnosis, and treatment of NLPHL are presented separately. (See "Nodular lymphocyte-predominant Hodgkin lymphoma: Clinical manifestations, diagnosis, and staging" and "Treatment of nodular lymphocyte-predominant Hodgkin lymphoma".)

The pathogenesis of HL and the role of Epstein-Barr virus in HL are discussed separately. (See "Pathogenesis of Hodgkin lymphoma".)

EPIDEMIOLOGY

Subtypes — Classic HL (cHL) accounts for approximately 90 percent of Hodgkin lymphoma, while nodular lymphocyte-predominant HL (NLPHL) accounts for the remainder of cases [2]. However, the distribution of histologic subtypes of cHL varies based on geography, socioeconomic factors, race/ethnicity, and age.

In the United States, Europe, and other economically developed regions, HL accounts for approximately 10 percent of all lymphomas (the remainder being non-Hodgkin lymphomas), 0.5 percent of all cancers, and 0.2 percent of all cancer deaths [3-5]. The incidence of HL in such settings has been stable at 2 to 3 cases per 100,000 persons for decades; in the United States, this corresponds to approximately 8500 new cases of HL annually, but the approximately 1000 annual deaths indicates a decreasing mortality rate.

The distribution of cHL subtypes in economically developed settings is [1]:

Nodular sclerosis cHL (NSCHL): 70 percent

Mixed cellularity cHL (MCCHL): 20 to 25 percent

Lymphocyte rich cHL (LRCHL): 5 percent

Lymphocyte depleted cHL (LDCHL): <1 percent

The distribution of cHL subtypes differs in other settings, and contributing factors include socioeconomic factors, age of exposure to Epstein-Barr virus (EBV), and prevalence of HIV/AIDS, as described below. (See 'Risk factors' below.)

Age and race — HL is most common among young adults (20 to 34 years); the median age at diagnosis is 39 years in the United States [6]. There is a bimodal age distribution with some histologic subtypes or geography (figure 1). The age distribution of patient ages varies with the histologic subtype:

Nodular lymphocyte-predominant HL (NLPHL) has a peak incidence in the fourth and fifth decades of life, but is also seen in children [2]. NLPHL is more common in males than in females. Other aspects of the epidemiology of NLPHL are discussed separately. (See "Nodular lymphocyte-predominant Hodgkin lymphoma: Clinical manifestations, diagnosis, and staging", section on 'Epidemiology'.)

Classic Hodgkin lymphoma (cHL) – The age and sex distribution varies with the cHL subtype. NSCHL has a peak incidence between ages 15 and 35 years, whereas MCCHL has a bimodal distribution with the peak in young adults and a second peak in older adults [1]. For NSCHL the incidence is comparable between males and females, but there is a male predominance for other subtypes of cHL [7,8].

The incidence of HL varies by race. As an example, from the SEER database, the incidence is equal in White and Black Americans in the United States (3.1 cases per 100,000 males), but it is lower in Hispanic Americans (2.6), Asians/Pacific Islanders, Native Americans, and Alaska natives [9]. In one population-based study (also using SEER), the peak incidence was in young adulthood among White and Black Americans and Asian/Pacific Islanders, but the peak in Hispanic Americans was in older individuals [10]. Compared to non-Hispanic White children, Hispanic children had an increased risk of HL (OR 2.43; 95% CI 1.14-5.17) and, in particular, were more often diagnosed with MCCHL [11].

RISK FACTORS

Overview — The incidence and distribution of HL histologic subtypes is influenced by geography, socioeconomic factors, HIV infection, and family history. Although Epstein-Barr virus (EBV) has been linked to the pathogenesis of HL, the virus is detected in only a subset of cases, and the absolute risk for HL after EBV infection is very small. (See 'Epstein-Barr virus' below.)

Importantly, there is an association between several of the risk factors for HL. As an example, compared with economically developed regions, there are higher rates of mixed cellularity classic HL (MCCHL) and lymphocyte-depleted classic HL (LDCHL) in geographic regions with lower socioeconomic development; these subtypes are more commonly associated with EBV-positive HL and higher rates of HIV infection [12-17].

Epstein-Barr virus — Detection of EBV in Hodgkin/Reed-Sternberg (HRS) cells varies with the histologic subtype, geography, and immunocompetence of the patient. EBV is most often associated with MCCHL and LDCHL subtypes, is more common in resource-limited settings, and is nearly always detected in HL of HIV-infected patients. The biology of EBV and mechanisms by which it may contribute to the pathogenesis of HL are discussed separately. (See "Virology of Epstein-Barr virus" and "Pathogenesis of Hodgkin lymphoma", section on 'Epstein-Barr virus'.)

Only a very small minority of patients infected with EBV will develop HL. Approximately 90 to 95 percent of adults worldwide are EBV seropositive, but the age of infection varies with socioeconomic conditions [18]. EBV is the cause of infectious mononucleosis (IM), and one study estimated that the absolute risk of developing HL after IM was approximately 1 in 1000 [19]. In this case-control study, there was an increased relative risk (RR) of developing EBV-positive HL after IM (RR 4.0; 95% CI 3.4-4.5), but no increased risk for EBV-negative HL [19]. There may be at higher risk of developing EBV-positive cHL in patients with certain genetic features. (See 'Genetic features' below.)

Epidemiologic, serologic, and pathologic data have identified the following associations of EBV with HL:

Histologic subtype – EBV positivity varies among the various histological categories of cHL: approximately 10 to 25 percent of NSCHL, 40 percent of LRCHL, 70 percent of MCCHL, and close to 100 percent of LDCHL [20,21]. EBV is rarely, if ever, found in NLPHL. Most cases of HL that carry inactivating mutations of immunoglobulin genes are EBV positive [22].

Geography – EBV is detected in the malignant cells of 20 to 50 percent of cases of classic HL (cHL) in North America and Europe, but nearly all cases of cHL are EBV positive in tropical and economically developing regions [12-17].

HIV/AIDS and other immunosuppressive conditions – Almost all HL cases occurring in patients with HIV infection or other immunosuppressive conditions are EBV positive, as discussed below. (See 'Immunosuppression' below.)

Other infections — There is controversy regarding a possible role for human herpesvirus 6 (HHV6) in HL pathogenesis, but there is currently no persuasive evidence that other types of infections play a causal role in HL [23].

HHV6 was detected in HRS cells of approximately half of NSCHL specimens in one study, based on immunodetection and molecular techniques on microdissected cells; HHV6 was more commonly found in younger patients with EBV-negative disease [24]. Other studies have also reported associations with HHV6 based on serologic and other techniques, but its contribution to the pathogenesis of HL is unclear [25-27].

There is no evidence that cytomegalovirus, human herpesviruses 7 and 8, polyoma JC virus, adenovirus types 5 and 12, human T cell lymphotropic virus 1 and 2, and human retrovirus 5 are present in HRS [28,29]. Certain childhood infectious illnesses, including chickenpox, measles, mumps, rubella, and pertussis, are negatively associated with the risk of HL [30]. A large population-based case-control study from Sweden reported an association between HL and certain infections (eg, sinusitis, tuberculosis, encephalitis, herpes zoster), but this may reflect an underlying immunodeficiency related to HL rather than a causal role for these infections [31]. (See 'Immunosuppression' below.)

Geography and socioeconomic status — The distribution of HL subtypes varies with geography and certain socioeconomic factors.

The distribution of histologic subtypes and age appears to parallel the level of industrial development in various geographic locales:

In the United States, Europe, and other economically advantaged countries, the highest incidence of HL is in older adolescents/young adults and there is a smaller peak in older adults (approximately age 65 years) (figure 1) [32]. Lymphomas are the most common cancer in adolescents (21 percent of new cancer diagnoses in those 15 to 19 years old) in such settings, and HL comprises approximately two-thirds of those cases [3].

In contrast, in economically disadvantaged areas, there is an initial peak in childhood for boys, relatively low rates in young adults, and a prominent peak in older adults [16,17,33].

An intermediate pattern with peaks of incidence both in childhood and in the second decade of life has been described in early industrialized or transitional economies [33-35].

In the developing world, MCCHL and LDCHL are relatively common HL subtypes whereas, in economically advantaged settings, NSCHL is the predominant subtype and LDCHL is rare [36,37]. The risk for MCCHL is inversely related to socioeconomic factors that are indicative of a higher standard of living, such as single family housing and small family size [38-40]. Among lower socioeconomic groups in economically advantaged settings, the predominant subtypes are MCCHL and LDCHL [41]. In Brazil, MCCHL is more common in rural regions, whereas NSCHL is more common in urban areas [42]. A population-based study in Israel reported a higher risk for NSCHL in Israeli-born individuals compared with immigrants (HR 1.59; 95% CI 1.32-1.92), which may reflect socioeconomic factors [43].

The associations between socioeconomic factors and disease incidence are generally taken to suggest that the development of HL is related to exposure to a common environmental or infectious agent, but the specific agent and/or exposure is not clear [28,44-49].

Other environmental factors — Although other environmental factors have been associated with the incidence of HL, no causal relationship has been proven and some of these factors may be associated with socioeconomic status. (See 'Geography and socioeconomic status' above.)

Diet, body weight: There is an increased risk of HL in association with obesity, based on population-based studies and a meta-analysis [50-52]. High intake of meat or sweets has been associated with an increased risk of cHL [53]. A positive association between physical inactivity and risk of HL was reported in 87 patients with HL compared with cancer-free controls [54].

Aspirin: A protective effect of aspirin for HL development has been reported, but results have varied across studies. In a case-control study of 565 patients with HL and 679 control subjects regular use of aspirin, but not other nonsteroidal anti-inflammatory drugs (NSAID), was associated with a lower risk of HL (odds ratio 0.60; 95% CI 0.42-0.85) [55]. A population-based study from northern Denmark reported a more modest, but not statistically significant, protective effect of aspirin [56]. The inverse association with aspirin consumption may reflect its effect on inhibiting NF-kB signaling, which is thought to play a key role in HL pathogenesis. (See "Pathogenesis of Hodgkin lymphoma", section on 'Pathogenesis of cHL'.)

Birth weight/breast feeding: High birthweight (after adjusting for birth order, maternal age at the age of the time of delivery, and paternal age) was associated with an increased risk of pediatric HL (OR 1.23; 95% CI 1.02-1.48) [57]. A protective effect of breastfeeding has been shown in multiple studies, but it is not known if this is related to transmitted maternal antibodies [58,59].

Cigarette smoking: A meta-analysis that analyzed 50 studies with nearly 5000 cases of HL reported that a history of ever-smoking was associated with increased risk for HL (pooled-effect estimate = 1.15, 95% CI 1.02-1.30); sizeable associations were observed regarding both NSCHL and MCCHL subtypes [60]. Several individual studies using various methodologies have reported an association between smoking and HL incidence [61-65].

Immunosuppression — The incidence of HL is increased in patients infected with HIV and in other settings associated with immunodeficiency. HL in these populations is almost universally positive for EBV. Although there is an increased incidence of HL in people infected with AIDS, HL is not considered an AIDS-defining malignancy. (See "HIV infection and malignancy: Epidemiology and pathogenesis", section on 'Non-AIDS-defining cancers'.)

The relative risk of HL has been reported to be increased 5- to 25-fold among patients infected with HIV [66-70]. In the United States, HIV infection is present in a substantial proportion of non-Hispanic Black, Hispanic, and middle-aged men with LDCHL and MCCHL [71]. The risk for HL is also increased in patients after solid organ transplantation, hematopoietic cell transplantation, and treatment with immunosuppressive drugs (eg, for autoimmune diseases) [72-76]. Rarely, cHL can arise as a Richter's transformation of chronic lymphocytic leukemia, and this occurrence may be related to immunosuppressive therapy (eg, fludarabine) or EBV [77]. Almost all HL cases occurring in the setting of HIV infection are EBV positive and many cases are LDCHL [78].

The risk for HL in immunosuppressed individuals is less striking than the risk for non-Hodgkin lymphomas (NHLs) [73,75]. The peak incidence of HL is four or more years after transplantation, in contrast to NHL, which most commonly occurs in the first year after transplantation. The CD4 T cell count associated with HIV-associated HL is typically higher than in other EBV-associated lymphomas. Further discussion of the association of immunosuppression and lymphomas is presented separately. (See "HIV-related lymphomas: Epidemiology, risk factors, and pathobiology" and "Malignancy after solid organ transplantation" and "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders".)

Autoimmune disorders — Patients with a history of autoimmune disorders are at increased risk for the development of HL, but it is unclear if this is directly related to these conditions or if it increased by the immunosuppressive agents used to treat them.

A population-based study of nearly 900,000 Swedes reported an increased standardized incidence ratio (SIR) for all subtypes of cHL (SIR 2.0; 95% CI 1.8-2.0) among patients with autoimmune illnesses, including polyarteritis nodosa, polymyositis/dermatomyositis, Behçet's disease, Sjögren's disease, polymyalgia rheumatica, and psoriasis [79]. A large population-based registry data study from Sweden and Denmark reported a strong association of HL with a personal or family history of autoimmune conditions [80]. Another population-based study reported an increased risk for HL in Danish patients with rheumatoid arthritis, but not with atopic diseases [81].

Familial risk — There is a familial predisposition to HL, but it is unclear how much of this effect is genetic versus environmental. The increased risk in close relatives of patients with HL is approximately three- to fivefold greater than the expected rate overall, but the risk may vary with the subtype [82-85]. In a registry-based study, the SIR for cHL was 5.3 (95% CI, 3.0 to 8.8) and SIR for NLPHL was 19 (95% CI, 8.8 to 36) in first-degree relatives of patients with HL [86]. The risk is stronger for HL in siblings than in parents [82,87-89].

Studies that reported increased familial risk for HL have used a variety of methodologies:

Case-control studies – A large Scandinavian case-control study reported a 3.3 odds ratio (OR) for HL in individuals of family history of HL [90]. Some smaller studies have reported larger ORs for HL [91,92].

Cohort studies – A cohort study of 3.5 million people in Sweden family history was associated with 7.2 and 8.5-fold increased risk of HL in children and young adults, respectively [87]. Another cohort study reported a sixfold increase for siblings [93].

Registry-based studies – A registry study from Sweden and Denmark reported a 3.1-fold increased risk (95% CI 1.8-5.3) [82,83]. In other registry-based studies, the risk of HL in first-degree relatives of HL probands ranged from 1.2 to 5.8-fold [88,89,94].

Monozygotic twins – In one study, compared to background rates, the SIR for HL in monozygotic twins was 99 (95% CI 48-182) [95]. Another study reported a 57-fold increased risk for HL in same sex twins [85].

Genetic features — The most consistent genetic association with risk for HL is variation at major histocompatibility complex (MHC)/human leukocyte antigen (HLA) loci. However, the increased risk for HL is most likely due to co-inheritance of multiple risk alleles, some which are likely to be common, rather than a single genetic determinant [96].

Variations at specific MHC/HLA loci are associated with an increased risk of developing HL. There is a consistent association with HLA-A1, and to a lesser extent, HLA-B5, HLA-B8, and HLA-B18 [97-103]. Genome-wide association studies (GWAS) identified specific MHC variants that were independently associated with both EBV-negative and EBV-positive cHL, while certain MHC variants that were independently associated with only EBV-positive cHL and other variants were only associated with EBV-negative cHL [103,104].

There has not been consistent identification of other genetic loci as risk factors for HL. A systematic review and meta-analysis of 21 studies identified some associations with various HLA loci, but no reproducible associations with candidate genes such as immune function/response, carcinogen metabolism enzymes, folate metabolism enzymes, DNA repair proteins, and others [96]. Some genes that have been reported to increase the risk for HL include REL, EOMES, ERAP1, IL13, PVT1, GATA3 and TCF3 [104-110].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Hodgkin lymphoma".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

Basics topics (see "Patient education: Hodgkin lymphoma in adults (The Basics)")

Beyond the Basics topics (see "Patient education: Hodgkin lymphoma in adults (Beyond the Basics)")

SUMMARY

Hodgkin lymphomas (HL), formerly called Hodgkin's disease, are lymphoid neoplasms in which malignant cells are admixed with a large, heterogeneous population of non-neoplastic inflammatory cells. HL is divided into two major subgroups, based on morphology and immunophenotype:

-Classic HL (cHL), which accounts for approximately 90 percent of HL:

-Nodular sclerosis cHL (NSCHL)

-Mixed cellularity cHL (MCCHL)

-Lymphocyte rich cHL (LRCHL)

-Lymphocyte depleted cHL (LDCHL)

Nodular lymphocyte-predominant HL (NLPHL) accounts for the remainder of HL

Epidemiology – The distribution of HL subtypes varies with geography and the level of economic development. In economically developed settings, NSCHL is the predominant subtype, followed by MCCHL, while LRCHL and LDCHL are uncommon. (See 'Subtypes' above.)

Age distribution – HL is most common among young adults (20 to 34 years) with a median of 39 years. HL has a bimodal age distribution with some histologic subtypes or geography (figure 1). (See 'Age and race' above.)

Epstein-Barr virus (EBV) is associated with the development of HL, but EBV is found in only a subset of cases of HL; involvement by EBV varies by age, geography, ethnicity, and histologic subtype. EBV infection is more common in resource-poor settings and is almost universally associated with HL in immunodeficient individuals (eg, HIV/AIDS). (See 'Epstein-Barr virus' above.)

Other risk factors that have been associated with HL include socioeconomic status, immunosuppression, and familial/genetic risks, as discussed above. (See 'Risk factors' above.)

  1. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition, Swerdlow SH, Campo E, Harris NL, et al. (Eds), International Agency for Research on Cancer (IARC), Lyon 2017.
  2. Laurent C, Do C, Gourraud PA, et al. Prevalence of Common Non-Hodgkin Lymphomas and Subtypes of Hodgkin Lymphoma by Nodal Site of Involvement: A Systematic Retrospective Review of 938 Cases. Medicine (Baltimore) 2015; 94:e987.
  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69:7.
  4. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
  5. Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105:1684.
  6. https://seer.cancer.gov/statfacts/html/hodg.html (Accessed on January 28, 2022).
  7. Au WY, Gascoyne RD, Gallagher RE, et al. Hodgkin's lymphoma in Chinese migrants to British Columbia: a 25-year survey. Ann Oncol 2004; 15:626.
  8. Morton LM, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 2006; 107:265.
  9. https://seer.cancer.gov/archive/csr/1975_2014/results_merged/sect_09_hodgkins.pdf (Accessed on April 17, 2019).
  10. Evens AM, Antillón M, Aschebrook-Kilfoy B, Chiu BC. Racial disparities in Hodgkin's lymphoma: a comprehensive population-based analysis. Ann Oncol 2012; 23:2128.
  11. Marcotte EL, Ritz B, Cockburn M, et al. Birth characteristics and risk of lymphoma in young children. Cancer Epidemiol 2014; 38:48.
  12. Araujo I, Bittencourt AL, Barbosa HS, et al. The high frequency of EBV infection in pediatric Hodgkin lymphoma is related to the classical type in Bahia, Brazil. Virchows Arch 2006; 449:315.
  13. Leoncini L, Spina D, Nyong'o A, et al. Neoplastic cells of Hodgkin's disease show differences in EBV expression between Kenya and Italy. Int J Cancer 1996; 65:781.
  14. Weinreb M, Day PJ, Niggli F, et al. The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya. Blood 1996; 87:3828.
  15. Weinreb M, Day PJ, Niggli F, et al. The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. Arch Dis Child 1996; 74:27.
  16. Barros MH, Hassan R, Niedobitek G. Disease patterns in pediatric classical Hodgkin lymphoma: a report from a developing area in Brazil. Hematol Oncol 2011; 29:190.
  17. Ferreira JM, Klumb CE, de Souza Reis R, et al. Lymphoma subtype incidence rates in children and adolescents: first report from Brazil. Cancer Epidemiol 2012; 36:e221.
  18. Gares V, Panico L, Castagne R, et al. The role of the early social environment on Epstein Barr virus infection: a prospective observational design using the Millennium Cohort Study. Epidemiol Infect 2017; 145:3405.
  19. Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 2003; 349:1324.
  20. Hummel M, Anagnostopoulos I, Dallenbach F, et al. EBV infection patterns in Hodgkin's disease and normal lymphoid tissue: expression and cellular localization of EBV gene products. Br J Haematol 1992; 82:689.
  21. Huppmann AR, Nicolae A, Slack GW, et al. EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults. Am J Surg Pathol 2014; 38:316.
  22. Bräuninger A, Schmitz R, Bechtel D, et al. Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma. Int J Cancer 2006; 118:1853.
  23. Wells MJ, Jacobson S, Levine PH. An evaluation of HHV-6 as an etiologic agent in Hodgkin lymphoma and brain cancer using IARC criteria for oncogenicity. Infect Agent Cancer 2019; 14:31.
  24. Siddon A, Lozovatsky L, Mohamed A, Hudnall SD. Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma. Br J Haematol 2012; 158:635.
  25. Lacroix A, Collot-Teixeira S, Mardivirin L, et al. Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein. Clin Cancer Res 2010; 16:4711.
  26. Levine PH, Ebbesen P, Ablashi DV, et al. Antibodies to human herpes virus-6 and clinical course in patients with Hodgkin's disease. Int J Cancer 1992; 51:53.
  27. Kashanchi F, Araujo J, Doniger J, et al. Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53. Oncogene 1997; 14:359.
  28. Jarrett RF, MacKenzie J. Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin's disease. Semin Hematol 1999; 36:260.
  29. Armstrong AA, Shield L, Gallagher A, Jarrett RF. Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin's disease. Br J Cancer 1998; 77:1045.
  30. Alexander FE, Jarrett RF, Lawrence D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
  31. Kristinsson SY, Gao Y, Björkholm M, et al. Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden. Int J Hematol 2015; 101:563.
  32. Ries LA, Kosary CL, Hankey BF, et al. (Eds). SEER cancer statistics review: 1973-1994, NIH publ no. 97-2789, National Cancer Institute, Bethesda 1997.
  33. Correa P, O'Conor GT. Epidemiologic patterns of Hodgkin's disease. Int J Cancer 1971; 8:192.
  34. Correa P, O'Conor GT. Geographic pathology of lymphoreticular tumors: summary of survey from the geographic pathology committee of the international union against cancer. J Natl Cancer Inst 1973; 50:1609.
  35. Gutensohn N, Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med 1981; 304:135.
  36. Biggar RJ, Jaffe ES, Goedert JJ, et al. Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. Blood 2006; 108:3786.
  37. Benharroch D, Levy A, Gopas J, Sacks M. Lymphocyte-depleted classic Hodgkin lymphoma-a neglected entity? Virchows Arch 2008; 453:611.
  38. Cozen W, Katz J, Mack TM. Risk patterns of Hodgkin's disease in Los Angeles vary by cell type. Cancer Epidemiol Biomarkers Prev 1992; 1:261.
  39. Glaser SL. Regional variation in Hodgkin's disease incidence by histologic subtype in the US. Cancer 1987; 60:2841.
  40. McNally RJ, Alston RD, Cairns DP, et al. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England. Br J Haematol 2003; 123:60.
  41. Hu E, Hufford S, Lukes R, et al. Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center. J Clin Oncol 1988; 6:1285.
  42. Elgui de Oliveira D, Bacchi MM, Abreu ES, et al. Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: characterization of clinicopathologic aspects and relationship with Epstein-Barr virus infection. Am J Clin Pathol 2002; 118:25.
  43. Levine H, Leiba M, Bar Zeev Y, et al. Risk of Hodgkin lymphoma according to immigration status and origin: a migrant cohort study of 2.3 million Jewish Israelis. Leuk Lymphoma 2017; 58:959.
  44. Flavell KJ, Biddulph JP, Powell JE, et al. South Asian ethnicity and material deprivation increase the risk of Epstein-Barr virus infection in childhood Hodgkin's disease. Br J Cancer 2001; 85:350.
  45. Vianna NJ, Greenwald P, Brady J, et al. Hodgkin's disease: cases with features of a community outbreak. Ann Intern Med 1972; 77:169.
  46. Vianna NJ, Polan AK. Epidemiologic evidence for transmission of Hodgkin's disease. N Engl J Med 1973; 289:499.
  47. Grufferman S, Cole P, Levitan TR. Evidence against transmission of Hodgkin's disease in high schools. N Engl J Med 1979; 300:1006.
  48. 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; 135:1454.
  49. Cozen W, Yu G, Gail MH, et al. Fecal microbiota diversity in survivors of adolescent/young adult Hodgkin lymphoma: a study of twins. Br J Cancer 2013; 108:1163.
  50. Strongman H, Brown A, Smeeth L, Bhaskaran K. Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individuals. Br J Cancer 2019; 120:768.
  51. 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; 108:2390.
  52. Larsson SC, Wolk A. Body mass index and risk of non-Hodgkin's and Hodgkin's lymphoma: a meta-analysis of prospective studies. Eur J Cancer 2011; 47:2422.
  53. Epstein MM, Chang ET, Zhang Y, et al. Dietary pattern and risk of hodgkin lymphoma in a population-based case-control study. Am J Epidemiol 2015; 182:405.
  54. Etter JL, Cannioto R, Soh KT, et al. Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study. Leuk Res 2018; 69:7.
  55. Chang ET, Zheng T, Weir EG, et al. Aspirin and the risk of Hodgkin's lymphoma in a population-based case-control study. J Natl Cancer Inst 2004; 96:305.
  56. Chang ET, Cronin-Fenton DP, Friis S, et al. Aspirin and other nonsteroidal anti-inflammatory drugs in relation to Hodgkin lymphoma risk in northern Denmark. Cancer Epidemiol Biomarkers Prev 2010; 19:59.
  57. Triebwasser C, Wang R, DeWan AT, et al. Birth weight and risk of paediatric Hodgkin lymphoma: Findings from a population-based record linkage study in California. Eur J Cancer 2016; 69:19.
  58. Grufferman S, Davis MK, Ambinder RF, et al. A protective effect of breast-feeding on risk of Hodgkin's disease in children. Paediatr Perinat Epidemiol 1998; 12:13.
  59. Davis MK, Savitz DA, Graubard BI. Infant feeding and childhood cancer. Lancet 1988; 2:365.
  60. Sergentanis TN, Kanavidis P, Michelakos T, Petridou ET. Cigarette smoking and risk of lymphoma in adults: a comprehensive meta-analysis on Hodgkin and non-Hodgkin disease. Eur J Cancer Prev 2013; 22:131.
  61. Nieters A, Rohrmann S, Becker N, et al. Smoking and lymphoma risk in the European prospective investigation into cancer and nutrition. Am J Epidemiol 2008; 167:1081.
  62. Castillo JJ, Dalia S, Shum H. Meta-analysis of the association between cigarette smoking and incidence of Hodgkin's Lymphoma. J Clin Oncol 2011; 29:3900.
  63. Kroll ME, Murphy F, Pirie K, et al. Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study. Br J Cancer 2012; 107:879.
  64. Kamper-Jørgensen M, Rostgaard K, Glaser SL, et al. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph). Ann Oncol 2013; 24:2245.
  65. Taborelli M, Montella M, Libra M, et al. The dose-response relationship between tobacco smoking and the risk of lymphomas: a case-control study. BMC Cancer 2017; 17:421.
  66. Grulich AE, Li Y, McDonald A, et al. Rates of non-AIDS-defining cancers in people with HIV infection before and after AIDS diagnosis. AIDS 2002; 16:1155.
  67. Dal Maso L, Franceschi S, Polesel J, et al. Risk of cancer in persons with AIDS in Italy, 1985-1998. Br J Cancer 2003; 89:94.
  68. Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol 2003; 21:3447.
  69. Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 2005; 97:425.
  70. Spina M, Berretta M, Tirelli U. Hodgkin's disease in HIV. Hematol Oncol Clin North Am 2003; 17:843.
  71. Shiels MS, Koritzinsky EH, Clarke CA, et al. Prevalence of HIV Infection among U.S. Hodgkin lymphoma cases. Cancer Epidemiol Biomarkers Prev 2014; 23:274.
  72. Goedert JJ, Coté TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351:1833.
  73. Tinguely M, Vonlanthen R, Müller E, et al. Hodgkin's disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states. Mod Pathol 1998; 11:307.
  74. Glaser SL, Clarke CA, Gulley ML, et al. Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greater San Francisco Bay Area, 1988-1998. Cancer 2003; 98:300.
  75. Garnier JL, Lebranchu Y, Dantal J, et al. Hodgkin's disease after transplantation. Transplantation 1996; 61:71.
  76. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med 2008; 148:728.
  77. Janjetovic S, Bernd HW, Bokemeyer C, Fiedler W. Hodgkin's lymphoma as a rare variant of Richter's transformation in chronic lymphocytic leukemia: A case report and review of the literature. Mol Clin Oncol 2016; 4:390.
  78. IARC monograph on the evaluation of carcinogenic risk to humans. A review of human carcinogens. Part B: Biological agents, vol 100; Lyon, France. IARC, 2012. (Available online at: https://monographs.iarc.fr/wp-content/uploads/2018/06/mono100B.pdf).
  79. Fallah M, Liu X, Ji J, et al. Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. Ann Oncol 2014; 25:1397.
  80. 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; 98:1321.
  81. Hollander P, Rostgaard K, Smedby KE, et al. Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma. Am J Epidemiol 2015; 182:624.
  82. Goldin LR, Pfeiffer RM, Gridley G, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 2004; 100:1902.
  83. Goldin LR, Björkholm M, Kristinsson SY, et al. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol 2009; 146:91.
  84. Hjalgrim H, Rasmussen S, Rostgaard K, et al. Familial clustering of Hodgkin lymphoma and multiple sclerosis. J Natl Cancer Inst 2004; 96:780.
  85. Kharazmi E, Fallah M, Pukkala E, et al. Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries. Blood 2015; 126:1990.
  86. Saarinen S, Pukkala E, Vahteristo P, et al. High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol 2013; 31:938.
  87. Crump C, Sundquist K, Sieh W, et al. Perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood. Am J Epidemiol 2012; 176:1147.
  88. Paltiel O, Schmit T, Adler B, et al. The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study. Cancer 2000; 88:2357.
  89. Altieri A, Hemminki K. The familial risk of Hodgkin's lymphoma ranks among the highest in the Swedish Family-Cancer Database. Leukemia 2006; 20:2062.
  90. Chang ET, Smedby KE, Hjalgrim H, et al. Family history of hematopoietic malignancy and risk of lymphoma. J Natl Cancer Inst 2005; 97:1466.
  91. Rudant J, Menegaux F, Leverger G, et al. Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE). Int J Cancer 2007; 121:119.
  92. Villeneuve S, Orsi L, Monnereau A, et al. Increased frequency of hematopoietic malignancies in relatives of patients with lymphoid neoplasms: a French case-control study. Int J Cancer 2009; 124:1188.
  93. Friedman DL, Kadan-Lottick NS, Whitton J, et al. Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev 2005; 14:1922.
  94. Pang D, Alston RD, Eden TO, Birch JM. Cancer risks among relatives of children with Hodgkin and non-Hodgkin lymphoma. Int J Cancer 2008; 123:1407.
  95. Mack TM, Cozen W, Shibata DK, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med 1995; 332:413.
  96. Sud A, Hemminki K, Houlston RS. Candidate gene association studies and risk of Hodgkin lymphoma: a systematic review and meta-analysis. Hematol Oncol 2017; 35:34.
  97. Oza AM, Tonks S, Lim J, et al. A clinical and epidemiological study of human leukocyte antigen-DPB alleles in Hodgkin's disease. Cancer Res 1994; 54:5101.
  98. Harty LC, Lin AY, Goldstein AM, et al. HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease. Blood 2002; 99:690.
  99. Kamper PM, Kjeldsen E, Clausen N, et al. Epstein-Barr virus-associated familial Hodgkin lymphoma: paediatric onset in three of five siblings. Br J Haematol 2005; 129:615.
  100. Diepstra A, Niens M, Vellenga E, et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma. Lancet 2005; 365:2216.
  101. Huang X, Kushekhar K, Nolte I, et al. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups. Blood 2011; 118:5211.
  102. Cozen W, Li D, Best T, et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood 2012; 119:469.
  103. Huang X, Kushekhar K, Nolte I, et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7:e39986.
  104. Urayama KY, Jarrett RF, Hjalgrim H, et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104:240.
  105. Sud A, Thomsen H, Law PJ, et al. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. Nat Commun 2017; 8:1892.
  106. Cerhan JR, Slager SL. Familial predisposition and genetic risk factors for lymphoma. Blood 2015; 126:2265.
  107. Hindorff LA, Sethupathy P, Junkins HA, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 2009; 106:9362.
  108. Frampton M, da Silva Filho MI, Broderick P, et al. Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma. Nat Commun 2013; 4:2549.
  109. Enciso-Mora V, Broderick P, Ma Y, et al. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Nat Genet 2010; 42:1126.
  110. Cozen W, Timofeeva MN, Li D, et al. A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus. Nat Commun 2014; 5:3856.
Topic 4691 Version 48.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟