Some pesticides and synthetic chemicals are known to act as hormonal modulators, often possessing oestrogenic activity (xenooestrogens). They are persistent and accumulate in fatty tissue. Aim of our study is to address the question, whether a selection of such compounds is to be found in the fatty tissue of children undergoing surgical procedures and whether there are differences in values obtained from patients with or without undescended testes. Fat samples of 48 patients, 18 of whom had undescended testes, were examined by high-resolution gas chromatography and mass spectrometry for DDT and metabolites, polychlorinated biphenyls (PCB), toxaphenes, hexachlorocyclohexane (HCH), chlorinated cyclodienes and chlorinated benzenes. We were able to find accumulation of all substances in every patient. Statistical analysis revealed a highly significant difference between patients from the control group and those from the undescended testes group for two compounds, namely heptachloroepoxide (HCE) and hexachlorobenzene (HCB), increased values being found in the patients with undescended testes. Since the aetiology of this entity is unknown in most of the cases, prenatal exposure to exogenous oestrogens is an attractive and plausible hypothesis. In order to confirm this, some questions will have to be answered in further studies: effect of exposure to xenooestrogens during a specific period of development, probable role of other substances with proven or suspected hormonal activity, potential synergism of such compounds and differences in individual susceptibility.

PurposeThe recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities.MethodsThe consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case–parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data.ResultsCurrently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents.ConclusionFirst results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.

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