A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma

Cozen, Wendy; Hamilton, Ann S.; Zhao, Peng; Salam, Muhammad T.; Deapen, Dennis; Nathwani, Bharat N.; Weiss, Lawrence M.; Mack, Thomas M.

doi:10.1182/blood-2009-03-209601

Cited by 54 publications

(54 citation statements)

References 42 publications

(54 reference statements)

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“…35 Substantial evidence supports the hypothesis that NSHL results from an atypical immune response to a virus 4 or another biologic trigger in the setting of a Th2-skewed immune response. 6,13,15,16 Genetic variation in HLA class II genes may underlie this aberrant response, because such variation results in structural alterations in the HLA molecule-binding pockets, and therefore potentially in binding capacity difference for specific antigens. 36 In addition, HLA class II alleles can influence CD4 ϩ T-cell polarization to either the Th1 or Th2 subtype with subsequent alterations in cytokine responses.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] NSHL is not associated with a history of infectious mononucleosis, whereas MCHL is strongly associated. [5][6] Histologically, most NSHL tumors are EBV Ϫ and contain wide bands of sclerotic tissue; accordingly, the mRNA geneexpression pattern is reminiscent of wound healing and collagen synthesis. [7][8] In contrast, the majority of MCHL tumors are EBV ϩ and the gene-expression pattern of MCHL suggests inflammation.…”

Section: Introductionmentioning

confidence: 99%

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A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Cozen

Best

et al. 2012

Blood

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Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P ‫؍‬ 5.35 ؋ 10 ؊10 ), rs204999 (P ‫؍‬ 1.44 ؋ 10 ؊9 ), and rs2858870 (P ‫؍‬ 1.69 ؋ 10 ؊8 ). We also confirmed a previously reported association in the same region, rs6903608 (P ‫؍‬ 3.52 ؋ 10 ؊10 ). rs204999 and rs2858870 were weakly correlated (r 2 ‫؍‬ 0.257), and the remaining pairs of SNPs were not correlated (r 2 < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR ‫؍‬ 1.7, P ‫؍‬ 1.71 ؋ 10 ؊6 ; GAATC, OR ‫؍‬ 0.4, P ‫؍‬ 1.16 ؋ 10 ؊4 ). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR ‫؍‬ 0.5, 95% confidence interval ‫؍‬ 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology. (Blood. 2012;119(2): 469-475) IntroductionHodgkin lymphoma (HL) is a B-cell lymphoid malignancy defined by the presence of the malignant Hodgkin/Reed-Sternberg cell. It is composed of diverse etiologic and pathologic subtypes distinguished by histology, age at diagnosis, and EBV tumor status. Since the World Health Organization Revised European-American Lymphoma (REAL) classification was introduced in 2000, nodular sclerosing Hodgkin lymphoma (NSHL) has often been combined with mixed-cellularity Hodgkin lymphoma (MCHL) and other subtypes as classic Hodgkin lymphoma (cHL). 1 However, abundant evidence suggests that NSHL is an etiologic entity distinct from other subtypes. NSHL is the most common histologic subtype among adolescents and young adults in industrialized countries. 2 The risk of NSHL increases according to the level of economic development and is associated with childhood isolation. [2][3][4] This suggests a strong childhood environmental influence, a pattern not seen for MCHL. 2-4 NSHL is not associated with a history of infectious mononucleosis, whereas MCHL is strongly associated. [5][6] Histologically, most NSHL tumors are EBV Ϫ and contain wide bands of sclerotic tissue; accordingly, the mRNA geneexpression pattern is reminiscent of wound healing and collagen synthesis. [7][8] In contrast, the majority of MCHL tumors are EBV ϩ and the gene-expression pattern of MCHL suggests inflammation. [7][8] Therefore, NSHL has a morphologic and risk pattern that differs from that of MCHL and should be considered a distinct etiologic entity. 1 NSHL is also among the most heritable of neoplasms, with a 1...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Cozen

Best

et al. 2012

Blood

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“…Thus an advantaged childhood as a risk indicator does not serve to exclude either of the hypotheses that could explain the link to economic development/higher socioeconomic status. Although we could not add to the evidence suggesting that diagnosis follows a deficiency of early acquired immunity (7,65), the major finding of a protected family environment certainly supports that hypothesis.…”

Section: Discussionmentioning

confidence: 78%

“…Affluent parents are likely to be more protective of only children, or children without siblings near in age, and less protective of individual children in large sib-ships. In a study of twins discordant for AYAHL, we found that the twin who reported, and was reported to have, more early oral exposures was five times more likely to be the affected twin (65).…”

Section: Discussionmentioning

confidence: 99%

“…They also had experienced more frequently reported past infectious In contrast with the inverse association between childhood infection and AYAHL, another marker of childhood infection, tonsillectomy, which usually occurs at a later age, has repeatedly been found to be associated with risk (37,60,(79)(80)(81)(82)(83)(84)(85), although often without appropriate adjustment for other determinants. While it actually may act as a measure of better access to care (a surrogate for high social class), it has also been found associated with AYAHL in a study of disease-discordant twins (65), uniquely matched on genome, childhood environment, and presumably access to care. Here, we also found a positive (albeit nonsignificant) association with that operation as well as with appendectomy.…”

Section: Discussionmentioning

confidence: 99%

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Childhood Determination of Hodgkin Lymphoma among U.S. Servicemen

Mack

Norman

Rappaport

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Hodgkin lymphoma in young adults is inexplicably linked to economic development.Methods: We conducted a nested case-control study of the 656 servicemen with Hodgkin lymphoma diagnosed between ages 17 to 32 while on active duty in the U.S. military during 1950-68. Controls, chosen randomly from the servicemen on duty at the time, were matched on service, birth year, and induction date. Information came from preinduction records and military records for the period ending at onset or the equivalent date.

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The microbiome in pediatric oncology

Rotz

Dandoy

2020

Cancer

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The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.

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A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma

Cited by 54 publications

References 42 publications

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Childhood Determination of Hodgkin Lymphoma among U.S. Servicemen

The microbiome in pediatric oncology

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