Familial aggregation of early‐onset cancers

Heikkinen, Sanna; Madanat‐Harjuoja, Laura; Seppä, Karri; Rantanen, Matti; Hirvonen, Elli; Malila, Nea; Pitkäniemi, Janne

doi:10.1002/ijc.32512

Cited by 21 publications

(24 citation statements)

References 27 publications

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“…Our findings also confirm and strengthen the evidence of common familial risks for childhood CNS tumours and leukaemia, and are consistent with a wide range of studies 44,45,46,47 The biological mechanisms behind the associations found in the present study might be explained by genetic and environmental factors or interaction between them. However, studies conducted in first-degree relatives suffer from inability to discern between possible environmental effects or shared genetic susceptibility.…”

Section: Discussionsupporting

confidence: 93%

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population‐based study in Utah and Norway

Kollerud¹,

Cannon-Albright

Haugnes

et al. 2020

Pediatric Blood & Cancer

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In this study we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumours in the central nervous system (CNS) and leukaemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. MethodsWe used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. ResultsThe overall incidence of CNS tumours increased with consecutive birth cohorts similarly in Utah and Norway (both p<0.001). Incidence rates of leukaemia were more stable and similar in both Utah and in Norway with 4.6/100,000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumours was significantly associated with risk of childhood CNS tumours in Utah HR= 3.05(95% CI 1.80-5.16) and Norway HR= 2.87(95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukaemia had high risk of leukaemia (HR= 2.39, 95% CI 1.61-3.55). ConclusionDespite geographical distance and assumed large life style differences, two genetically linked paediatric populations show similar incidences of CNS tumours and leukaemia in the period 1966-2015. CNS tumours and leukaemia aggregated in families in both countries.

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Section: Discussionsupporting

confidence: 93%

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population‐based study in Utah and Norway

Kollerud¹,

Cannon-Albright

Haugnes

et al. 2020

Pediatric Blood & Cancer

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“…Follow‐up ended either at the date of first diagnosis of childhood and young adult (ChYA) cancer, attainment of age 40 years, date of emigration or death, or December 31, 2016, whichever came first. The identification of family members and follow‐up for both family members and probands has been described previously 20 …”

Section: Methodsmentioning

confidence: 99%

Linking population‐based registries to identify familial cancer risk in childhood cancer

Madanat‐Harjuoja

Pitkäniemi

Hirvonen

et al. 2020

Cancer

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Background Linked population‐based registries provide a unique source for identification of new family cancer syndromes and for elucidating risk of early‐onset cancer in close relatives of cancer patients. Methods Using the Finnish Cancer Registry, we identified 9078 probands who had been diagnosed with cancer at <21 years of age between 1970 and 2012. Siblings, offspring, parents, nephews, and nieces of probands were identified from the Population Registry. Childhood and young adult (ChYA) cancer diagnoses (age 0‐39 years) in relatives were identified by linking to the Finnish Cancer Registry. The relative risk of ChYA cancer in family members of probands was estimated using standardized incidence ratios (SIRs). Results Among 58,010 family members of the 9078 probands, 363 ChYA cancers were diagnosed, 324 of which were expected (SIR, 1.12; 95% CI, 1.01‐1.24). The risk of ChYA cancer was elevated both in offspring (SIR, 2.25; 95% CI, 1.51‐3.24) and in siblings (SIR, 1.17; 95% CI, 1.01‐1.36). Offspring of probands with retinoblastoma were at highest risk (SIR, 75.85; 95% CI, 32.75‐149.45); risks were also elevated for siblings of probands with lymphoma (SIR, 1.62; 95% CI, 1.14‐2.25). Known cancer predisposition syndromes were observed in 29 (66%) of 44 sibling pairs with cancers diagnosed at <21 years of age and in 20% of the 135 families with a childhood cancer proband whose sibling was diagnosed with a young adult malignancy. Conclusion Linked population‐based registry data indicate a modestly increased risk of ChYA in relatives of children with cancer. Some of the observed cancer clusters in the cohort suggest novel patterns and familial cancer syndromes.

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“…Another cohort that can be approached to test this hypothesis are those patients with familial clustering, in whom inherited genetic susceptibility has been ruled out. Two such cohorts have been identified in Scandinavia ( 107 , 108 ). The cohort of patients with breast cancer in the study by Heikkinen et al ( 107 ) is a perfect example of a testable study group.…”

Section: Testing the Hypothesis And Its Implicationsmentioning

confidence: 99%

“…Two such cohorts have been identified in Scandinavia ( 107 , 108 ). The cohort of patients with breast cancer in the study by Heikkinen et al ( 107 ) is a perfect example of a testable study group.…”

Section: Testing the Hypothesis And Its Implicationsmentioning

confidence: 99%

Young-Onset Carcinogenesis – The Potential Impact of Perinatal and Early Life Metabolic Influences on the Epigenome

Barreto

Pandol

2021

Front. Oncol.

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The last decade has witnessed a significant rise in cancers in young adults. This spectrum of solid organ cancers occurring in individuals under the age of 40 years (some reports extending the age-group to <50 years) in whom aetiology of cancer cannot be traced back to pre-existing familial cancer syndromes, is referred to as termed young-, or early- onset cancers. The underlying causes for young-onset carcinogenesis have remained speculative. We recently proposed a hypothesis to explain the causation of this entity. We propose that the risk for young-onset cancer begins in the perinatal period as a result of the exposure of the foetus to stressors, including maternal malnutrition, smoking or alcohol, with the consequent epigenomic events triggered to help the foetus cope/adapt. Exposure to the same stressors, early in the life of that individual, facilitates a re-activation of these ‘responses designed to be protective’ but ultimately resulting in a loss of regulation at a metabolic and/or genetic level culminating in the evolution of the neoplastic process. In this manuscript, we will provide a rationale for this hypothesis and present evidence to further support it by clarifying the pathways involved, including elucidating a role for Acetyl-CoA and its effect on the epigenome. We present strategies and experimental models that can be used to test the hypothesis. We believe that a concerted effort by experts in different, but complementary fields, such as epidemiology, genetics, and epigenetics united towards the common goal of deciphering the underlying cause for young-onset cancers is the urgent need. Such efforts might serve to prove, or disprove, the presented hypothesis. However, the more important aim is to develop strategies to reverse the disturbing trend of the rise in young-onset cancers.

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Familial aggregation of early‐onset cancers

Cited by 21 publications

References 27 publications

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population‐based study in Utah and Norway

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population‐based study in Utah and Norway

Linking population‐based registries to identify familial cancer risk in childhood cancer

Young-Onset Carcinogenesis – The Potential Impact of Perinatal and Early Life Metabolic Influences on the Epigenome

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