Is the risk of acute lymphoblastic leukemia reduced in siblings to children with the disease? A novel hypothesis explored by international collaboration

Schmiegelow, Kjeld; Hjalgrim, Henrik

doi:10.1038/sj.leu.2404250

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…On the other hand, the HLA-DPB1*0201 allele, belonging to the HLA class II genes that are important in adaptive immune responses to infection, has been shown to be significantly more common in children with hyperdiploid ALL than in healthy infants, suggesting that it increases the risk for this type of ALL (Taylor et al, 2002). Hence, there may be genetic risk factors for high hyperdiploid ALL, but based on available evidence, in particular that siblings-twins excluded-to children with ALL do not have an increased risk of ALL (Schmiegelow and Hjalgrim, 2006), constitutional genetics does not seem to be a major etiologic factor. …”

Section: Genetic Risk Factorsmentioning

confidence: 93%

High hyperdiploid childhood acute lymphoblastic leukemia

Paulsson

Johansson

2009

Genes Chromosomes & Cancer

171

183

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High hyperdiploidy (51-67 chromosomes) is the most common cytogenetic abnormality pattern in childhood B-cell precursor acute lymphoblastic leukemia (ALL), occurring in 25-30% of such cases. High hyperdiploid ALL is characterized cytogenetically by a nonrandom gain of chromosomes X, 4, 6, 10, 14, 17, 18, and 21 and clinically by a favorable prognosis. Despite the high frequency of this karyotypic subgroup, many questions remain regarding the epidemiology, etiology, presence of other genetic changes, the time and cell of origin, and the formation and pathogenetic consequences of high hyperdiploidy. However, during the last few years, several studies have addressed some of these important issues, and these, as well as previous reports on high hyperdiploid childhood ALL, are reviewed herein.

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Section: Genetic Risk Factorsmentioning

confidence: 93%

High hyperdiploid childhood acute lymphoblastic leukemia

Paulsson

Johansson

2009

Genes Chromosomes & Cancer

171

183

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“…Apart from a higher incidence among children carrying specific predisposition genes, the disease is generally unclustered in families [1] and populations [2,3]. Anecdotal observations of clustering of childhood leukemia have led investigators to hypothesize specific causes of the clusters, ranging from population mixing and unique viruses in naïve populations to chemical exposures from point sources [4–13].…”

Section: Introductionmentioning

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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“…Second, if there is a maternally driven protective mechanism against recurrence of the subsets of ALL commonly initiated prenatally (most notably high-hyperdiploid or ETV6-RUNX1-positive cases), the concordance rate could be significantly lower than that expected by chance. 21…”

Section: Introductionmentioning

confidence: 99%

High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia

et al. 2011

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Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N = 51) or more (N = 3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83 ± 0.05. Ages at diagnosis (Spearman correlation coefficient, r(S) = 0.41, P = 0.002) were significantly correlated, but not WBCs (r(S) = 0.23, P = 0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N = 3), t(12;21) [ETV6/RUNX1] (N = 1), MLL rearrangement (N = 1) or t(1;19)(q23/p13) (N = 1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N = 5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N = 6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P < 0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors.

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Is the risk of acute lymphoblastic leukemia reduced in siblings to children with the disease? A novel hypothesis explored by international collaboration

Cited by 6 publications

References 19 publications

High hyperdiploid childhood acute lymphoblastic leukemia

High hyperdiploid childhood acute lymphoblastic leukemia

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

High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia

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