The familial risk of Hodgkin's lymphoma ranks among the highest in the Swedish Family-Cancer Database

Altieri, Andrea; Hemminki, Kari

doi:10.1038/sj.leu.2404378

Cited by 28 publications

(26 citation statements)

References 10 publications

(16 reference statements)

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“…Excess risk has been reported in siblings 5 and family members 6 of cases, and we found a greater excess risk in identical (monozygotic, MZ) cotwins compared with fraternal (dizygotic, DZ) cotwins of cases. 7 An immune response phenotype associated with altered cytokine levels constitutes a likely candidate for a heritable risk factor since the pathological and clinical hallmark of Hodgkin lymphoma is immune dysregulation.…”

Section: Introductionsupporting

confidence: 62%

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Cozen

Gill

Salam

et al. 2008

Blood

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Young adult Hodgkin lymphoma (YAHL)is associated clinically with altered immunity, including a systemic defect in cellmediated responses. There is strong evidence of a genetic contribution to risk, so we hypothesized that heritable alterations in cytokine production associated with Th1 function may contribute to susceptibility. We identified twin pairs in whom at least one member had YAHL and measured interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-␥ (IFN-␥) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in 90 case-twins, 84 of their disease-free twins (unaffected cotwins), and 90 matched controls. Mean difference and mean percentage difference in cytokine levels between casetwins and controls, and unaffected cotwins and controls were determined using analysis of covariance. YAHL casetwins and their unaffected cotwins had IL-12 levels that were 60.6% (P ‫؍‬ .002) and 49% (P ‫؍‬ .04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in casetwins (P ‫؍‬ .049), but not unaffected cotwins (P ‫؍‬ .57), compared with controls. Differences in IFN-␥ levels were not statistically significant in either comparison. An IL-12 polymorphism known to regulate expression was associated with a 2.8-fold (P ‫؍‬ .03) increase in YAHL risk. Thus, both case-twins and their unaffected cotwins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility. IntroductionHodgkin lymphoma is characterized by 3 distinctive age-specific incidence peaks associated with different demographic factors, probably representing distinct etiologies. 1 Young adult Hodgkin lymphoma (YAHL), diagnosed approximately from ages 13 to 45 years, consists mainly of an Epstein-Barr virus (EBV)-negative, nodular sclerosis subtype, and has been historically strongly (positively) correlated with higher socioeconomic status and low sibship size. 2 These factors suggest an association between early childhood isolation from infection and risk, consistent with delayed exposure to a common childhood infection ("polio model"). 3 Although Epstein-Barr virus infection would be consistent with this set of factors, the best study to date found no increased risk of EBV-negative Hodgkin lymphoma, the most common type of YAHL, among 40 000 persons with laboratory-documented infectious mononucleosis. 4 (The same study did demonstrate a 20-fold risk of EBV-positive Hodgkin lymphoma within 5 years of the infectious mononucleosis diagnosis, but EBV-positive Hodgkin lymphoma accounts for only 10% to 25% of the disease in young adults.)Genetic factors also contribute to YAHL susceptibility. Excess risk has been reported in siblings 5 and family members 6 of cases, and we found a greater excess risk in identical (monozygotic, MZ) cotwins compared with fraternal (dizygotic, DZ) cotwins of cases. 7 An immune response phenotype associated with altered cytokine levels constitutes a likely candidate for a heritable risk factor since the pathological and clinical hallmark of Hodgkin ly...

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Section: Introductionsupporting

confidence: 62%

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Cozen

Gill

Salam

et al. 2008

Blood

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“…Large population-based registry-linked studies have investigated the familial aggregation of Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL) or leukemia. [3][4][5][6][7] In children, few population-based registry-linked studies have been published, [8][9][10][11][12][13] most of them relating to first-degree relatives. [8][9][10][11][12] The estimated relative risks for a positive family history of cancer ranged from 0.8 to 1.0 for childhood leukemia 8,[10][11][12][13] and from 1.0 to 1.8 for childhood lymphoma taken as a whole.…”

Section: ]) Thementioning

confidence: 99%

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non‐Hodgkin's lymphoma: The ESCALE study (SFCE)

Rudant

Ménégaux

Leverger

et al. 2007

Intl Journal of Cancer

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The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population‐based case–control study, was carried out in France over the period, 2003–2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non‐Hodgkin's lymphoma (NHL) and 1,681 population‐based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first‐ and second‐degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0–2.2]) and NHL (OR = 1.8 [1.3–2.5]), but not AL (OR = 1.0 [0.9–1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0–3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3–22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL. © 2007 Wiley‐Liss, Inc.

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“…15,16,20 Few studies have provided familial risks by sex of the patient and the relative, suggesting gender concordance among sibling pairs with HL. 15,21,22 The rarity of familial classical HL has hampered a detailed analysis of familial clustering by relationship, histology, age, and sex, and it has probably contributed to the variation even in risk estimates for first-degree relatives.…”

Section: Introductionmentioning

confidence: 99%

Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries

Kharazmi

Fallah

Pukkala

et al. 2015

Blood

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Key Points• We provide clinically relevant familial risk estimates for classical HL patients by relationship, histology, age at diagnosis, and sex.We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by relationship, histology, age at diagnosis, and sex. A cohort of 57 475 first-degree relatives of 13 922 HL patients diagnosed between 1955 and 2009 in 5 European countries was observed for HL incidence. The overall lifetime cumulative risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence interval [CI], 2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 95% CI, 4.8-to 7.4-fold) was significantly higher than in parents and/or children (2.1-fold; 95% CI, 1.6-to 2.6-fold). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 95% CI, 2.8-to 39-fold) and for same-sex twins (57-fold; 95% CI, 21-to 125-fold). We found high familial risks between some concordant histologic subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30-to 177-fold) and nodular sclerosis (4.6-fold; 95% CI, 2.9-to 7.0-fold) and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9-to 14-fold) was higher than in brothers (4.5-fold; 95% CI, 2.9-to 6.7-fold) or unlike-sex siblings (5.9-fold; 95% CI, 4.3-to 8.1-fold). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30 years). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical HL by oncologists and genetic counselors.

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The familial risk of Hodgkin's lymphoma ranks among the highest in the Swedish Family-Cancer Database

Cited by 28 publications

References 10 publications

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non‐Hodgkin's lymphoma: The ESCALE study (SFCE)

Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries

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