Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Azevedo-Silva, Fernanda; Camargo, Beatriz de; Pombo-de-Oliveira, Maria do Socorro

doi:10.1590/s0100-879x2010007500011

Cited by 6 publications

(5 citation statements)

References 15 publications

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“…Schmiegelow et at proposed the hypothalamus-pituitary-adrenal axis hypothesis in which infections at early stage of life may alter plasma cortisol levels 46 . This can result in elimination of leukemic cells and reduce the risk of ALL 46 , 47 . Moreover, there is evidence that vaccines, both viral and bacterial, also have the ability to raise the plasma cortisol 48 – 51 .…”

Section: Discussionmentioning

confidence: 99%

Early vaccination protects against childhood leukemia: A systematic review and meta-analysis

Morra

Kien

Elmaraezy

et al. 2017

Sci Rep

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Leukemia is the most commonly diagnosed childhood cancer, although its etiology is still largely unknown. Growing evidence supports a role for infection in the etiology of acute lymphocytic leukemia (ALL), and the involvement of the immune system suggests that vaccination may also play a role. However, the findings presented in the published literature are inconsistent. Therefore, we conducted a PRISMA systematic review and meta-analysis. 14 studies were identified and meta-analyzed. Vaccinations studied comprised Bacillus Calmette-Guérin (BCG) vaccine, Triple vaccine, Hepatitis B vaccine (HBV), Polio, Measles, Rubella, Mumps, trivalent MMR vaccine and Haemophilus influenza type B (HiB) vaccine. We observed a protective association between any vaccination in the first year of life and risk of childhood leukemia (summary odds ratio (OR) 0.58 [95% confidence interval (CI) 0.36–0.91]). When individual vaccines were analysed, some evidence of an association was seen only for BCG (summary OR 0.73 [95% CI 0.50–1.08]). In conclusion, early vaccination appears to be associated with a reduced risk of childhood leukemia. This finding may be underpinned by the association observed for BCG. Given the relatively imprecise nature of the results of this meta-analysis, our findings should be interpreted cautiously and replicated in future studies.

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Section: Discussionmentioning

confidence: 99%

Early vaccination protects against childhood leukemia: A systematic review and meta-analysis

Morra

Kien

Elmaraezy

et al. 2017

Sci Rep

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“…Furthermore, the immune system can adapt to high infectious loads preventing a more reactive inflammatory response induced by Th1 cytokines in that cortisol favors the production of anti-inflammatory Th2 cytokines. Azevedo-Silva et al 4 show differences in ALL incidence rates across Brazilian regions. Salvador and Aracaju, cities in the Northeast, had the lowest rates, while Curitiba, Southeast, and Goiania, Midwest, had the highest.…”

Section: Discussionmentioning

confidence: 98%

Infection and childhood leukemia: review of evidence

Maia¹,

Filho²

2013

Rev. Saude Publica

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OBJECTIVETo analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia.METHODSA search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia.RESULTSOverall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori.CONCLUSIONSAlthough no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

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“…The state of Amazonas, located in the Amazonian region of Brazil, is known for its tropical climate and a highly heterogeneous population that is exposed to several pathogens. In addition, it has different endemic areas for infectious diseases, which could contribute to the modulation of the immune response and consequently the triggering of physiological, genetic, and hematological changes 30 . The biological pro le of ALL is still little known, and has different patterns according to the geographic and ethnic regions of the world 4,[30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Clinical Implication of SNVs in TLR Genes in Pediatric Patients From the Brazilian Amazon With Acute Lymphoblastic Leukemia

Xabregas

Hanna

Souza

et al. 2022

Preprint

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Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy and the leading cause of childhood mortality. Single-nucleotide variants (SNVs) in key molecules of the immune system, such as Toll-like receptors (TLRs) and CD14 molecule, are associated with the development of several diseases. However, their role in ALL is unknown. A case-control study was performed with 152 ALL patients and 187 healthy individuals to investigate the role of SNVs in TLRs and the CD14 gene in ALL. In this study, TLR6 C > T rs5743810 [95% CI: 3.20, OR: 1.11–9.17, p = 0.003) and TRL9 C/T rs187084 (95% CI: 2.29, OR: 1.23–4.26, p = 0.000) seems to be a risk for development of ALL. In addition, the TLR4 A > G rs4986791 polymorphism was associated with protection from infectious comorbidities (IC 95%adj: 0.18, ORadj:0.02–1.50, p = 0.058) and the TRL1 T > G rs5743618 and TRL6 C > T rs5743810 polymorphisms with protection against death (95% IC: 0.17, OR: 0.04–0.79, p = 0.008; 95% IC: 0.48, OR: 0.24–0.94, p = 0.031, respectively). Our results show that SNVs in TLR genes may be involved in the pathogenesis of ALL and may influence clinical prognosis; however, further studies are necessary to elucidate the role of TLR1, TLR4, TLR5, TLR9 and CD14 polymorphisms in this disease.

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Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Cited by 6 publications

References 15 publications

Early vaccination protects against childhood leukemia: A systematic review and meta-analysis

Early vaccination protects against childhood leukemia: A systematic review and meta-analysis

Infection and childhood leukemia: review of evidence

Clinical Implication of SNVs in TLR Genes in Pediatric Patients From the Brazilian Amazon With Acute Lymphoblastic Leukemia

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