Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls

Vasconcelos, Gisele M.; Kang, Michelle; Pombo‐de‐Oliveira, Maria S.; Schiffman, J. D.; Lorey, Fred; Buffler, Patricia A.

doi:10.1038/sj.bjc.6604714

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…These results lead us to conclude that adenovirus DNA is not readily detected in the archived neonatal blood spots, irrespective of whether the subject subsequently develops leukaemia. Although the findings reported here fail to support our previously reported preliminary results (Gustafsson et al, 2007), these findings agree with those reported subsequently (Vasconcelos et al, 2008).…”

Section: Discussionsupporting

confidence: 79%

“…We recently reported that adenovirus DNA was detected in 13 of 51 Guthrie cards from ALL patients, but in only 6 of 47 healthy controls (P ¼ 0.0122, Fisher's exact test), indicating that adenovirus may be such a causative agent (Gustafsson et al, 2007). However, a subsequent study of twice as many paediatric ALL patients in California failed to find adenovirus DNA in the corresponding neonatal blood spots (Vasconcelos et al, 2008). This study sought to further examine the possibility of an association between prenatal adenovirus infection and ALL using a larger number of archived Swedish samples from children who later developed ALL and controls without the disease.…”

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confidence: 99%

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Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL)

et al. 2010

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BACKGROUND: In search of a proposed viral aetiology of childhood acute lymphoblastic leukaemia (ALL), the common species C adenoviruses were analysed in Guthrie cards. METHODS: Guthrie cards from 243 children who later developed ALL and from 486 matched controls were collected and analysed by nested polymerase chain reaction for the presence of adenovirus DNA. RESULTS: Adenovirus DNA was reliably detected from only two subjects, both of whom developed ALL. CONCLUSION: Adenovirus DNA is detected in Guthrie card samples at too low a frequency to reveal an association between adenovirus and the development of leukaemia.

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Section: Discussionsupporting

confidence: 79%

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confidence: 99%

Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL)

et al. 2010

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“…In contrast to the study of cord blood lymphocytes described here, most studies evaluating neonatal blood spots have failed to detect a variety of viruses [36] including adenovirus [11,12]. The detection of adenoviral DNA in dried blood spots faces several limitations.…”

Section: Discussionmentioning

confidence: 91%

Neonatal Infection with Species C Adenoviruses Confirmed in Viable Cord Blood Lymphocytes

2015

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Credible but conflicting reports address the frequency of prenatal infection by species C adenovirus. This question is important because these viruses persist in lymphoid cells and suppress double-stranded DNA-break repair. Consequently, prenatal adenovirus infections may generate the aberrant clones of lymphocytes that precede development of childhood acute lymphoblastic leukemia (ALL). The present study was designed to overcome technical limitations of prior work by processing cord blood lymphocytes within a day of collection, and by analyzing sufficient numbers of lymphocytes to detect adenovirus-containing cells at the lower limits determined by our previous studies of tonsil lymphocytes. By this approach, adenoviral DNA was identified in 19 of 517 (3.7%) samples, providing definitive evidence for the occurrence of prenatal infection with species C adenoviruses in a significant fraction of neonates predominantly of African American and Hispanic ancestry. Cord blood samples were also tested for the presence of the ETV6-RUNX1 translocation, the most common genetic abnormality in childhood ALL. Using a nested PCR assay, the ETV6-RUNX1 transcript was detected in four of 196 adenovirus-negative samples and one of 14 adenovirus-positive cord blood samples. These findings indicate that this method will be suitable for determining concordance between adenovirus infection and the leukemia-associated translocations in newborns.

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“…Despite the fact that environmental triggers have been proposed as part of the etiology for childhood leukemia for quite sometime, limited supportive data exist [44]. Investigations of viral infection in sporadic, unclustered childhood leukemia cases have not implicated any specific infections in such populations [45–49], but specific infections have not been adequately addressed in any leukemia cluster investigation. The spike in incident military childhood ALL cases during the same time period as the Fallon cluster support the hypothesis that a specific virus was introduced into the community by the large yearly influx of military personnel training at the base that was then transmitted/amplified by the mosquito population.…”

Section: Discussionmentioning

confidence: 99%

Unusual space-time patterning of the Fallon, Nevada leukemia cluster: Evidence of an infectious etiology

Francis

Selvin

Yang

et al. 2012

Chemico-Biological Interactions

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The town of Fallon within Churchill County, Nevada exhibited an unusually high incidence of childhood leukemia during the years 1997–2003. We examined the temporal and spatial patterning of the leukemia case homes in comparison to the distribution of the general population at risk, other cancer incidence, and features of land use. Leukemia cases were predominantly diagnosed during the early to mid summer, exhibiting a seasonal bias. Leukemia cases lived outside of the “developed/urban” area of Fallon, predominantly in the “agriculture/pasture” region of Churchill County, circumscribing downtown Fallon. This pattern was different from the distribution of the underlying population (p-value < 0.01) and different from the distribution of other cancers, which were evenly distributed when compared to the population (p-value = 0.74). The unusual space-time patterning of childhood leukemia is consistent with the involvement of an infectious disease. A possible mode of transmission for such an infectious disease is by means of a vector, and mosquitoes are abundant in Churchill County outside of the urban area of Fallon. This region harbors a US Navy base, and a temporally concordant increase in military wide childhood leukemia rates suggests the base a possible source of the virus. Taken together, our current understanding of the etiology of childhood leukemia, the rural structure combined with temporal and geospatial patterning of these leukemia cases, and the high degree of population mixing in Fallon, suggest a possible infectious cause.

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Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls

Cited by 17 publications

References 30 publications

Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL)

Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL)

Neonatal Infection with Species C Adenoviruses Confirmed in Viable Cord Blood Lymphocytes

Unusual space-time patterning of the Fallon, Nevada leukemia cluster: Evidence of an infectious etiology

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