Danièle Sommelet

A tumor profile in Down syndrome

We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.

Acute childhood leukaemia and environmental exposure to potential sources of benzene and other hydrocarbons; a case-control study

Aim: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. Methods: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. Results: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. Conclusions: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.

Cancer incidence among children in France, 1990–1999

Cancer is the second most important cause of death for children aged less than 15 years in France, unintentional injuries being the leading cause. The aim of the present study was to estimate the incidence of childhood cancer from six Childhood Cancer Registries covering 32% of France.

Household exposure to pesticides and risk of childhood acute leukaemia

Objectives: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. Methods: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. Results: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). Conclusion: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.

Incidence of childhood leukaemia and non-Hodgkin's lymphoma in France: National Registry of Childhood Leukaemia and Lymphoma, 1990-1999.

The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkins disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkins lymphomas and 6.7 for Hodgkins disease. Downs syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkins lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkins lymphoma did not show any temporal trends over the 10 year period.

Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy.

Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene–environment interactions were estimated using both case–control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0–4.9]) and with GSTM1 deletion (OR 2.3 [1.2–4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3–1.2] and 0.4 [0.1–1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.

Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as ‘primary’ (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the four girls studied exhibited a polyclonal pattern of X‐inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues.

Cancer incidence among adolescents in France.

In France, cancer ranks third as the most significant cause of mortality in young people. However, the incidence, the survival, and the management of adolescent cancers have never been studied. The aim of this study is to investigate incidence rate (IR) of adolescents with cancer from data recorded in French Cancer Registries covering eight administrative areas, representing 10% of the French population, over a 10‐year period (from 1988 to 1997).

Breast-feeding, fetal loss and childhood acute leukaemia

Abstract.The results presented support the hypothesis that prolonged breast-feeding may protect against childhood acute leukaemia and suggest an association with a maternal history of repeated miscarriages.

Pathways of care for adolescent patients with cancer in France from 2006 to 2007.

In France, as in other countries, there is a need for a population‐based view of access to care and modalities of treatment for adolescents with cancer.