Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome.

Children with Down syndrome (DS) have a 20-fold increased risk of acute lymphoblastic leukemia (ALL) and distinct somatic features, including CRLF2 rearrangement in ∼50% of cases; however, the role of inherited genetic variation in DS-ALL susceptibility is unknown. We report the first genome-wide association study of DS-ALL, comprising a meta-analysis of 4 independent studies, with 542 DS-ALL cases and 1192 DS controls. We identified 4 susceptibility loci at genome-wide significance: rs58923657 near IKZF1 (odds ratio [OR], 2.

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study).

Germline TP53 pathogenic variants are rare but associated with a high risk of cancer; they are often identified in the context of clinically diagnosed Li-Fraumeni syndrome predisposing to a range of young onset cancers including sarcomas and breast cancer. The study aim was to conduct a detailed morphological review and immuno-phenotyping of breast cancer arising in carriers of a germline TP53 pathogenic variant. We compared breast cancers from five defined groups: (1) TP53 carriers with breast cancer (n = 59), (2) early onset HER2-amplified breast cancer, no germline pathogenic variant in BRCA1/2 or TP53 (n = 55), (3) BRCA1 pathogenic variant carriers (n = 60); (4) BRCA2 pathogenic variant carriers (n = 61) and (5) young onset breast cancer with no known germline pathogenic variant (n = 98).

Risk of solid subsequent malignant neoplasms after childhood Hodgkin lymphoma-Identification of high-risk populations to guide surveillance: A report from the Late Effects Study Group.

Background: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations.

Methods: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference.

Factors associated with recurrence and survival length following relapse in patients with neuroblastoma.

Background: Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients.

Methods: All cases of relapsed neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric Oncology principal treatment centres.

Mutations in the transcriptional repressor REST predispose to Wilms tumor.

Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases.

UK case control study of brain tumours in children, teenagers and young adults: a pilot study.

Background: Tumours of the central nervous system are the second most common group of childhood cancers in 0-14 year olds (24% of total cancers) and represent a major diagnostic group in 15-24 year olds. The pilot case-control study aimed to establish methodologies for a future comprehensive aetiological investigation among children and young adults.

Methods: Eligible cases were newly diagnosed with an intracranial tumour of neuroepithelial tissue aged 0-24 years.

Fanconi anaemia, BRCA2 mutations and childhood cancer: a developmental perspective from clinical and epidemiological observations with implications for genetic counselling.

Fanconi anaemia (FA) is an inherited condition characterised by congenital and developmental abnormalities and a strong cancer predisposition. In around 3-5% of cases FA is caused by biallelic mutations in the BRCA2 gene. Individuals heterozygous for BRCA2 mutations have an increased risk of inherited breast and ovarian cancer.

Median percent change: a robust alternative for assessing temporal trends.

A typical summary statistic for temporal trends is the average percent change (APC). The APC is estimated by using a generalized linear model, usually under the assumption of linearity on the logarithmic scale. A serious limitation of least-squares type estimators is their sensitivity to outliers.

The role of SIOP as a platform for communication in the global response to childhood cancer.

Since the year 2000, there has been a 35% annual decrease in mortality among children under the age of five worldwide. The decrease is mainly attributed to the decrease in childhood epidemic infections, for example, due to vaccination programs. In the near future, this decrease will draw attention to paediatric non-communicable diseases (NCDs), and cancer is one of the most common.

Malignant peripheral nerve sheath tumours in inherited disease.

Background: Malignant peripheral nerve sheath tumours (MPNST) are rare tumours known to occur at high frequency in neurofibromatosis 1 (NF1), but may also occur in other cancer prone syndromes.

Methods: The North West Regional Genetic Register covers a population of 4.1 million and was interrogated for incidence of MPNST in 12 cancer prone syndromes.

Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003.

Background: It is believed that gonadal and extragonadal germ cell tumors (GCTs) arise from primordial germ cells and may have similar etiopathogenesis. Unlike testicular GCTs, there has been limited comprehensive population-based analysis of ovarian and extragonadal GCTs.

Methods: All malignant GCTs and all central nervous system (CNS) GCTs with benign and uncertain behavior that were registered in England in the age group 0 to 84 years from 1979 to 2003 were included in the current study.

The contrasting age-incidence patterns of bone tumours in teenagers and young adults: Implications for aetiology.

Bone tumours comprise 0.2% of cancers overall but 5.7% in 15-24 year olds.

Relationship between height at diagnosis and bone tumours in young people: a meta-analysis.

Objective: Some evidence exists that patients with osteosarcoma and Ewing sarcoma are taller than the general population. However, previous studies are under-powered, lack comprehensive data and show inconsistencies.

Methods: Relevant studies linking osteosarcoma and Ewing sarcoma with height at diagnosis were identified in two major online databases, Medline (1950 to 2009) and Embase (1980 to 2009).

Cancer at ages 15-29 years: the contrasting incidence in India and England.

Background: There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15-29 years in India and England.

Are reported increases in incidence of primary CNS tumours real? An analysis of longitudinal trends in England, 1979-2003.

Reported increases in the incidence of CNS tumours in the developed world in the 1970s to 1990s have been a cause for concern and debate. It still remains to be adequately answered whether these increases are true or an artefact of changes in diagnostic and registration practices. Using high-quality national cancer registration data, we have analysed incidence trends for each major histological subgroup of CNS tumour (2000 World Health Organisation (WHO) classification) registered in those aged 0-84 years for the whole of England during the period 1979 through 2003.

Age-incidence patterns of primary CNS tumors in children, adolescents, and adults in England.

Around 25% of all tumors in those 0-14 years of age and 9% in those 15-24 years of age involve the CNS. They are the most common cause of cancer-related deaths in both age groups. In adults 25-84 years of age, the proportion of CNS tumors is 2%; 5-year overall survival is 10%-15%; and survivors have considerable morbidity.

Changes in cancer incidence in teenagers and young adults (ages 13 to 24 years) in England 1979-2003.

Background: Cancer for teenagers and young adults represents a major source of morbidity and mortality. Trends in cancer incidence can provide pointers concerning how changes in the environment and in personal behavior affect cancer risks.

Methods: Data on 39,129 neoplasms in individuals ages 13 to 24 years who were diagnosed in England from 1979 to 2003 were analyzed.

Cancer risks among relatives of children with Hodgkin and non-Hodgkin lymphoma.

A role for genetic susceptibility in the aetiology of childhood lymphomas was investigated in 454 families of children with histologically confirmed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) from Northwest England. Cancers in parents were obtained from the UK National Health Service Central Register and in other close relatives by interview with the parents. The cancer incidence among relatives was compared with expected incidence based on cancer registry data for England.

Registration and classification of adolescent and young adult cancer cases.

Cancer registries are an important research resource that facilitate the study of etiology, tumor biology, patterns of delayed diagnosis and health planning needs. When outcome data are included, registries can track secular changes in survival related to improvements in early detection or treatment. The surveillance, epidemiology, and end results (SEER) registry has been used to identify major gaps in survival for older adolescent and young adult (AYA) patients compared with younger children and older adults.

HLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention.

Most childhood B cell precursor (BCP) acute lymphoblastic leukaemia (ALL) cases carry the reciprocal translocation t(12;21)(p13;q22) ( approximately 25%), or a high hyperdiploid (HeH) karyotype (30%). The t(12;21) translocation leads to the expression of a novel fusion gene, TEL-AML1 (ETV6-RUNX1), and HeH often involves tri- and tetrasomy for chromosome 21. The presence of TEL-AML1+ and HeH cells in utero prior to the development of leukaemia suggests that these lesions play a critical role in ALL initiation.

Cervical paraganglioma--a case report and review of all cases reported to the Manchester Children's Tumour Registry 1954-2004.

We report a 6-year-old male with left-sided ptosis, aniscoria and an initially missed slow growing left-sided neck mass, which was surgically excised when he was 9 years old and confirmed to be a paraganglioma. Seven years later he developed recurrent symptoms and was found to have a recurrence in the anterior mediastinum. We also report on all cases of cervical paragangliomas registered with the Manchester Children's Tumour Registry (MCTR) for the 50-year period 1954-2004.

Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy.

Purpose: Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy.

Patients And Methods: We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy.