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Logan G Spector

Publications and source records attributed to Logan G Spector.

12 recordsLinked to original sources
PubMed2026

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗
PubMed2026

RAG-mediated structural variation and its impact on relapse risk in acute lymphoblastic leukemia.

Relapse during treatment of B-cell acute lymphoblastic leukemia (B-ALL) is a harbinger of poor outcomes. Identifying biomarkers for subsequent relapse risk which are detectable at B-ALL diagnosis remains a priority. Off-target recombination-activating gene (RAG)-mediated structural variants (SVs) generate genomic instability that drives leukemogenesis and may underlie treatment resistance. Leveraging sequencing data in 1,496 pediatric B-ALL patients enriched for relapse status (relapse n=532; non-relapse n=964), we characterized RAG-mediated SVs across B-ALL molecular subtypes and examined their association with patient characteristics and their impact on clinical outcomes. Off-target RAG-mediated SVs were overall frequent, particularly in ETV6::RUNX1, ETV6::RUNX1-like, and Ph-like B-ALL subtypes, while increasing age-at-diagnosis was positively associated with burden of off-target RAG-mediated SVs (P<.001). Off-target RAG-mediated SVs with a recombination signal sequence (RSS) at one breakpoint, a hallmark of off-target RAG activity, were significantly more frequent at diagnosis in patients who subsequently relapsed (P=.001). This association remained significant in multivariable regression analysis (per SV odds ratio [OR]:1.08, 95%CI:1.04-1.12), in minimal residual disease (MRD)-negative patients (OR:1.09, 95%CI:1.04-1.14) and across subtypes. Excluding deletions, MRD-negative ETV6::RUNX1 patients with &#x2265;3 off-target RAG-mediated SVs had a >3-fold risk of relapse (hazard ratio:3.47, 95% CI:1.86-6.49). RAG-mediated SVs were also associated with relapse risk in T-cell ALL patients. Off-target RAG-mediated SV burden at diagnosis is a risk factor of relapse in pediatric ALL across molecular subtypes and independent of MRD status.

Journal Article↗
PubMed2007

Birth characteristics, maternal reproductive history, and the risk of infant leukemia: a report from the Children's Oncology Group.

Leukemias with MLL gene rearrangements predominate in infants (<1 year of age), but not in older children, and may have a distinct etiology. High birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL(+), 80 MLL(-), and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, pre-pregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL(+) (P = 0.06), but not MLL(-) (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL(+) (P = 0.01), but not MLL(-) (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies.

Adult↗
PubMed2006

Child and maternal household chemical exposure and the risk of acute leukemia in children with Down's syndrome: a report from the Children's Oncology Group.

Compared with the general pediatric population, children with Down's syndrome have a much higher risk of acute leukemia. This case-control study was designed to explore potential risk factors for acute lymphoblastic leukemia and acute myeloid leukemia in children with Down's syndrome living in the United States or Canada. Mothers of 158 children with Down's syndrome and acute leukemia (97 acute lymphoblastic leukemia, 61 acute myeloid leukemia) diagnosed between January 1997 and October 2002 and mothers of 173 children with Down's syndrome but without leukemia were interviewed by telephone. Positive associations were found between acute lymphoblastic leukemia and maternal exposure to professional pest exterminations (odds ratio = 2.25, 95% confidence interval: 1.13, 4.49), to any pesticide (odds ratio = 2.18, 95% confidence interval: 1.08, 4.39), and to any chemical (odds ratio = 2.72, 95% confidence interval: 1.17, 6.35). Most of the associations with acute myeloid leukemia were nonsignificant, and odds ratios were generally near or below 1.0. This exploratory study suggests that household chemical exposure may play a role in the development of acute lymphoblastic leukemia in children with Down's syndrome.

Adult↗
PubMed2005

Epidemiology of leukemia in children with Down syndrome.

Studies suggest nearly a 20-fold increased risk of leukemia in individuals with Down syndrome. Most of this increased risk appears in the first few decades of life, with the highest incidence in children less than 5 years of age. It is unknown why children with Down syndrome are at such an increased risk of leukemia. With respect to environmental exposures, it will be important to investigate risk factors associated with childhood leukemia in general (including diagnostic x-rays, pesticides, and other occupational exposures) as well as experiences common to children with Down syndrome (including routine medical screening tests, increased susceptibility to infections, and increased vitamin deficiencies).

Adolescent↗
PubMed2005

Childhood cancer following neonatal oxygen supplementation.

OBJECTIVE: To evaluate the relationship between neonatal oxygen supplementation (O2) and childhood cancer in the Collaborative Perinatal Project (CPP). STUDY DESIGN: The CPP consisted of 54,795 children born between 1959 and 1966 and followed to age 8 years. We used Cox proportional hazards modeling to examine the association between history of neonatal O2 and cancer (n = 48). RESULTS: The hazard ratio (HR) for any O2 was 1.77 (95% confidence interval [CI] = 0.94 to 3.35). The HR for continuous duration of O2 was near 1 and not significant. However, the HRs were 0.69 (95% CI = 0.17 to 2.88) and 2.87 (95% CI = 1.46 to 5.66) when comparing 0 to 2 and 3 or more minutes of O2, respectively, to no O2. The latter association was weaker (HR = 2.00; 95% CI = 0.88 to 4.54) and not significant ( P = .10) when analysis was restricted to cancers diagnosed after age 1 year (n = 41). CONCLUSIONS: These findings are consistent with an association between O 2 for 3 minutes or longer and cancer in childhood, and should serve as a basis for further study.

Child↗
PubMed2005

Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.

Acute Disease↗
PubMed2003

Bias in studies of parental self-reported occupational exposure and childhood cancer.

Several case-control studies have demonstrated positive associations between parental occupational exposures and childhood cancer. However, an overestimation of risk estimates due to recall bias is of concern. The magnitude and nature of this bias were explored using data from a German case-control study on childhood leukemia conducted between 1992 and 1997. A moderate overreporting of occupational exposures by fathers was observed, particularly for the prenatal period. Overreporting was most apparent when the time between exposure and interview was short. It was also found that job titles were no satisfactory substitute for information on specific occupational exposures. The results of this analysis emphasize the need for more sophisticated exposure assessment methods in epidemiologic studies of childhood cancer. However, because future case-control studies will at least partially rely on questionnaire data, improvements including probing questions, better interview techniques, and validation studies are indicated.

Adolescent↗