The risk of cancer in twins: A report from the childhood cancer survivor study

Kadan‐Lottick, Nina S.; Kawashima, Toana; Tomlinson, Gail E.; Friedman, Debra L.; Yasui, Yutaka; Mertens, Ann C.; Robison, Leslie L.; Strong, Louise C.

doi:10.1002/pbc.20465

Cited by 21 publications

(15 citation statements)

References 30 publications

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“…The blood-borne nature of these hematologic malignancies would also explain why other pediatric cancer types do not show similarly high concordance in monozygotic, monochorionic twins. 34 However, the majority of twins are dichorionic, and approximately 8% demonstrate blood group chimerism because of placental fusion allowing blood exchange. 35 Despite this frequency and multiple reports of twin–twin transfusion syndrome in dichorionic twins, 36, 37, 38, 39, 40, 41 we found only one report of concordant IL in dichorionic twins because of the leukemia clone passing between infants, not through inter-placental anastomosis, but through the maternal circulation and not resulting in leukemia in the mother, only the other twin.…”

Section: Discussionmentioning

confidence: 99%

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children’s Oncology Group report

et al. 2013

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Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. While most cases are accompanied by MLL-rearrangements and harbor very few somatic mutations; less is known about the genetics of the cases without MLL translocations. We performed the largest exome sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared to randomly selected genes within the same patients and unaffected pediatric controls. IL AML patients had more overall variation than IL ALL patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins.

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Section: Discussionmentioning

confidence: 99%

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children’s Oncology Group report

et al. 2013

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“…[29][30][31][32][33][34][35] Even though monozygotic twins commonly share a placenta, and may exchange prenatally initiated preleukemic cells, 36 the concordance rate in twins for childhood ALL is only 10-25%, with the exception of high concordance rate in infant ALL with MLL rearrangement. 35,37,38 Accordingly, it has been suggested that a larger proportion of healthy newborns harbor preleukemic cells, 39 and that postnatal environmental factors influence the subsequent, often complex, malignant transformation. 2,35,40 However, the frequencies and levels of preleukemic cells in healthy newborns are debated.…”

Section: Discussionmentioning

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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“…Future efforts in sib-pair or twin studies 46 may further our understanding of the sibling relationships, particularly for the male-and femalespecific associations for family history of NHL and leukemia, respectively. Family studies in those with family history of HL or MM may also reveal factors influenced by the father that confer excess risk.…”

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confidence: 99%

Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)

Wang

Slager

Brennan

et al. 2006

Blood

157

123

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A role for genetic susceptibility in nonHodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR ‫؍‬ 1.5; 95% CI ‫؍‬ 1.2-1.9), Hodgkin lymphoma (OR ‫؍‬ 1.6; 95% CI ‫؍‬ 1.1-2.3), and leukemia (OR ‫؍‬ 1.4; 95% CI ‫؍‬ 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR ‫؍‬ 2.8; 95% CI ‫؍‬ 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR ‫؍‬ 1.7; 95% CI ‫؍‬ 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR ‫؍‬ 3.0; 95% CI ‫؍‬ 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology. (Blood.

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The risk of cancer in twins: A report from the childhood cancer survivor study

Cited by 21 publications

References 30 publications

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children’s Oncology Group report

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children’s Oncology Group report

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

Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)

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