J R Mann

The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma

The inter-regional epidemiological study of childhood cancer analysed data on 234 children diagnosed with leukaemia or lymphoma and 468 controls matched for age and sex. A wide range of potential risk factors was examined, including prenatal exposure to x rays, maternal drug ingestion and smoking, childs medical history, and parental medical conditions and occupation. Calculations were completed for leukaemia or lymphoma and diagnostic subgroups, as defined by laboratory confirmed cell type. In utero exposure to narcotic analgesics was weakly associated with leukaemia or lymphoma but no other antenatal factors gave significant risks. New associations were identified for skin diseases in both parents and congenital abnormalities in the mothers of children with leukaemia. For past medical conditions in the child, viral disease occurring under 6 months of age increased the risk for acute lymphoblastic leukaemia. Fewer children in the leukaemia or lymphoma group had been immunised compared with the control groups. Case children diagnosed over the age of 9 years were more likely than controls to have had four or more previous episodes of illness. Overall, these results indicate that prenatal factors may be less important than postnatal or genetic influences in the development of leukaemia or lymphoma in children.

Childhood Cancer and Parental Use of Tobacco:Findings from the Inter-Regional Epidemiological Study of Childhood Cancer [IRESCC]

Parental smoking data have been re-abstracted from the interview records of the Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) to test further the hypothesis that paternal cigarette smoking is a risk factor for the generality of childhood cancer. Reported cigarette smoking habits for the parents of 555 children diagnosed with cancer in the period 1980–1983 were compared, in two separate matched pairs analyses, with similar information for the parents of 555 children selected from GP lists (GP controls) and for the parents of 555 hospitalized children (hospital controls). When cases were compared with GP controls there was a statistically significant positive trend (P = 0.02) between the risk of childhood cancer and paternal daily consumption of cigarettes before the pregnancy; there was no significant trend for maternal smoking habit. When cases were compared with hospital controls there was a statistically significant negative trend (P< 0.001) between the risk of childhood cancer and maternal daily consumption of cigarettes before the pregnancy; there was no significant trend for paternal smoking habit. Neither of the significant trends could be explained by adjustment for socioeconomic grouping, ethnic origin or parental age at the birth of the child, or by simultaneous analysis of parental smoking habits. Relations between maternal consumption of cigarettes and birth weights suggested that (maternal) smoking data were equally reliable for case and control subjects, although comparisons with national data suggested that the hospital control parents were unusually heavy smokers. These findings give some support for the hypothesis that paternal cigarette smoking is a potential risk factor for the generality of childhood cancers.

ULTRASOUND EXAMINATIONS IN PREGNANCY AND CHILDHOOD CANCER

Analysis of information obtained in an inter-regional epidemiological study by interviewing the parents of 555 children with malignancy diagnosed between 1980 to 1983 and the parents of 1110 control children did not reveal any significant association between exposure to ultrasound examination in pregnancy and risk of childhood cancer.

The inter-regional epidemiological study of childhood cancer (IRESCC): case control study of children with bone and soft tissue sarcomas

The Inter-Regional Epidemiological Study of Childhood Cancer included 43 cases of soft tissue and 30 cases of bone sarcomas, together with their 146 matched controls. Analysis of a wide range of aetiological factors revealed few risk factors relating to events during the index pregnancy, the earlier medical experiences of the case child, or parental medical, occupational and smoking history. Associations which did emerge included: lower birth weight in children with Ewings tumour, an excess of mothers of children with soft tissue sarcoma with symptoms of toxaemia in pregnancy; and more children with rhabdomyosarcoma who received antibiotics soon after birth. There was some evidence that mothers of children with soft tissue sarcoma may have had reduced fertility with a significant excess of the case mothers having no other pregnancies. Slight excesses of congenital malformations in the case children and of malignant and benign/borderline neoplastic disease in the older mothers were consistent with the existence of a degree of genetic predisposition in the development of the tumours in this series.

Congenital abnormalities in children with cancer and their relatives: results from a case-control study (IRESCC * )

Several studies have revealed an excess of malformations in children with certain malignancies. A few environmental causes have been identified which may damage the foetus and lead to malformation and cancer. However, most of the numerous recognised cancer/malformation syndromes are genetically determined. This report describes a case-control study of 555 newly diagnosed children with cancer and 1,110 matched controls, chosen from general practitioner lists (GP controls) and hospital admissions (H controls). Their parents were interviewed on topics of possible aetiological significance and medical records were checked to confirm reports at interview. The numbers of congenital malformations in the index and GP control children, and the relatives of the index children, the GP and H controls are described. There were more children with malformations among the cases (60/555) than among the GP controls (27/555), P < 0.001. The abnormalities in the cases included eight with specific chromosomal/genetic conditions (e.g. Downs syndrome, XY gonadal dysgenesis, Von Recklinghausens neurofibromatosis, Goldenhars syndrome) whereas only one GP control child had a chromosomal defect (P < 0.05). Five case children but no GP controls had neural tube defects; this is not statistically significant. No excess of malformations was found in the siblings of cases compared with GP and H control siblings. Case mothers had a small excess of malformations (22/555) compared with GP controls (8/555), P < 0.05. Among more distant relatives the results were difficult to interpret because of the relatively small numbers in the diagnostic subgroups and because of apparent under reporting in grandparents, but no striking differences were seen between case and control relatives. The excess of malformations found in children with cancer, compared with controls, without a similar excess of malformations in their close relatives may indicate that in some (perhaps very roughly one in 20) cases antenatal events may lead both to the malformation and the malignancy.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the childs past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.

Is the risk of cancer increased in Asians living in the UK

The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi) children living in the West Midlands Health Authority Region was investigated using age standardised incidence rates. Two sets of rates were calculated, a 10 year rate (1982-91) using survey based estimates of the ethnic population and a four year rate (1989-92) using the ethnic population counts from the 1991 census. The 10 year rates showed a significantly higher annual incidence of cancer in Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers in Asian children was different, with an excess of lymphomas and germ cell tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the four year rates. Although underestimation of the Asian population probably contributes to the apparent excess, there remains cause for concern that UK Asian children may be at higher risk of cancer. Accurate ethnic population figures and confirmatory studies are urgently required.

Cancer and congenital abnormalities in Asian children: a population-based study from the West Midlands

Cancer and associated congenital abnormalities were investigated in Muslim and non-Muslim Asian children from the West Midlands. Cancer incidence rates were calculated for Indian (non-Muslim), Pakistani/Bangladeshi (Muslim) and white children diagnosed from 1978 to 1992. Incidence was significantly higher in the Pakistanis, with an age-standardised rate (ASR) of 163 cases per million per year, compared with 115 for Indian and 125 for white children. Among Asian cancer patients, congenital malformations were significantly more common in Muslim (21%) compared with non-Muslim (7%). In Muslims the malformation excess was caused by autosomal recessive and dominant disorders (in 8% and 5% of cases respectively). Cancer malformation/predisposition syndromes were found in 10% of Muslims, compared with 2% of non-Muslims. In 33% of the Muslims with malformations, childhood cancer and a malformation were also present in a close relative. None of the non-Muslims with malformations had a relative with childhood cancer. The cancer excess in Muslims may be partly related to inherited genes causing both malformations and cancer. The prevalence of autosomal recessive disorders may be related to consanguinity, which is common in the Pakistani Muslim population. The high incidence of autosomal dominant disorders may be related to older paternal age at conception, giving rise to spontaneous mutations.

Factors affecting survival in White and Asian children with acute lymphoblastic leukaemia.

Some studies suggest that Asian children with leukaemia have a worse outcome than Whites. Survival of Asians with ALL treated at the Birmingham Children’s Hospital from 1975 to 1994 was the same as that of Whites, despite their greater deprivation and poorer nutrition. For one 5-year period (1980–1984) Asians had significantly poorer survival, even after adjustment for prognostic factors. Poor treatment compliance during that period may have contributed to this difference.

Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): childhood cancer and the consumption of debendox and related drugs in pregnancy.

Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.