Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?

Vajdic, Claire M.; Mao, Limin; Leeuwen, Marina T. van; Kirkpatrick, Philippa; Grulich, Andrew E.; Riminton, Sean

doi:10.1182/blood-2010-03-272351

Cited by 112 publications

(97 citation statements)

References 42 publications

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“…Confounding by these conditions, although not the objective of this report, can be easily assessed by assigning the condition to one of the cells in Table 2. For example, common variable immune deficiency has a prevalence of approximately 1 in 30,000 live births (42) and an increased risk of leukemia (43), although the magnitude is not known. Based on our results, even if leukemia risk was substantially increased, confounding bias would be negligible given the low prevalence.…”

Section: Discussionmentioning

confidence: 99%

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes

Meulepas¹,

Ronckers²,

Merks³

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children.Methods: We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients.

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Section: Discussionmentioning

confidence: 99%

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes

Meulepas¹,

Ronckers²,

Merks³

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…HIV infection [13] and other immunodeficiency disorders [14,15] are associated with a higher risk of infection-related cancer. According to recent estimates, up to 40% of cancer cases among HIV-infected persons in the United States are infection related [16], an attributable fraction 10 times as high as in the general population.…”

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confidence: 99%

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

et al. 2016

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Background. In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.Methods. Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.Results. There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low-to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.Conclusions. Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.

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“…Numerous examples show that a reduced V(D)J recombinase activity affects the extent of antigenic diversity of immune receptors in mice and humans. The resulting immune deregulation may then lead to autoimmunity, increased susceptibility to infections, or the development of various forms of cancer (12).…”

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confidence: 99%

Cernunnos Deficiency Reduces Thymocyte Life Span and Alters the T Cell Repertoire in Mice and Humans

Vera

Rivera-Munoz

Abramowski

et al. 2013

Molecular and Cellular Biology

122

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f Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected. In particular, Cernunnos is dispensable during V(D)J recombination in lymphoid cells. Nevertheless, the viability of thymocytes is reduced in Cernunnos KO mice, owing to the chronic activation of a P53-dependent DNA damage response. This translates into a qualitative alteration of the T cell repertoire to one in which the most distal V␣ and J␣ segments are missing. This results in the contraction of discrete T cell populations, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, in both humans and mice.T he immune system is the site of intense genome dynamics, in particular during the development and maturation of B and T lymphocytes in bone marrow and the thymus, when antigen receptor genes are rearranged through V(D)J recombination prior to their expression. DNA damages are also likely to occur during the several phases of intense proliferation which accompany the development of B and T cells.V(D)J recombination is the prototypical example of the generation of a programmed DNA double-strand break (DNA-dsb) during lymphoid development through the activity of recombination activating genes 1 and 2 (Rag1/2) on immunoglobulin (Ig) and T cell receptor (TCR) genes (see the work of Helmink and Sleckman [1] for a recent review). The resulting DNA-dsb is resolved by the nonhomologous end-joining (NHEJ) DNA repair pathway, composed of seven core components (see the work of Lieber [2] for a recent review). The Cernunnos-Xrcc4-DNA ligase IV complex ultimately reseals the DNA-dsb. Cernunnos, also known as Xrcc4-like factor (XLF), was the last NHEJ factor that was independently identified, through a survey of RS-SCID patients (3) and a yeast two-hybrid screen with Xrcc4 as a bait (4). Cernunnos and Xrcc4 adopt the same overall three-dimensional crystal structure (5, 6) and, together with DNA ligase IV, are parts of the same complex (4, 7). Cernunnos stimulates the DNA-joining activity of the Xrcc4-DNA ligase IV complex (8, 9). V(D)J recombination constitutes a central checkpoint in the development of the immune system, as its defect leads to abortive B and T cell maturation in vivo, resulting in severe combined immune deficiency (SCID) (10), but its first recognized function was the generation of a diverse antigenic repertoire through the combinatorial association of variable, diversity, and joining segments that encode the variable domains of both Ig and TCRs (11). Numerous examples show that a reduced V(D)J recombinase activity affects the extent of antigenic diversity of immune receptors in mice and humans. The resulting immune deregulation may then lead to autoimmunity, increased susceptibility to infections, or the development of vario...

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Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?

Abstract: Analysis of cancer risk in primary im

Cited by 112 publications

References 42 publications

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

Cernunnos Deficiency Reduces Thymocyte Life Span and Alters the T Cell Repertoire in Mice and Humans

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