Energy restriction at young age,genetic variants in the insulin‐like growth factor pathway and colorectal cancer risk in the Netherlands Cohort Study

The energy restriction (ER)‐colorectal cancer (CRC) association is inconsistent in literature. To strengthen the biological plausibility of the ER‐CRC association, we investigated whether genetic variation in the insulin‐like growth factor (IGF) pathway, a putative underlying mechanism, modulated this association in the Netherlands Cohort Study. Participants completed a questionnaire (n = 120,852) and provided toenail clippings for DNA (～75%) at baseline. Individuals living in a Western city during the Hunger Winter (1944–45) or Western rural versus non‐Western area were exposed to (severe) ER at young age. Genotyping was performed for 3,768 subcohort members and 2,580 CRC cases (case‐cohort with 16.3 years follow‐up). Cox hazard ratios for CRC were estimated across combined categories of ER and a genetic sum score of unfavorable alleles based on 18 single nucleotide polymorphisms in IGF‐related genes and ER and an IGF1 19‐CA repeat polymorphism. The reference included ER exposed individuals, so that increased hazard ratios were expected in higher combined categories for calculating relative excess risks due to interaction (additive interactions). Wald tests for multiplicative interactions were also performed. Multiplicative and additive interactions were nonsignificant. Combined ER‐genetic sum score categories showed increasing CRC risks in men, but confidence intervals were wide. Women carrying two variant IGF1 19‐CA repeat alleles versus those carrying two wild type IGF1 19‐CA repeat alleles were at an ～50% decreased CRC risk, irrespective of ER exposure. In conclusion, data indicate that the IGF pathway might be involved in the ER‐CRC association in men, but not women, although interactions were nonsignificant, hampering definite conclusions.     

Molecular evidence for dissemination of unique Campylobacter jejuni clones in Curaçao, Netherlands Antilles

Campylobacter jejuni isolates (n = 234) associated with gastroenteritis and the Guillain-Barré syndrome (GBS) in the island of Cura?ao, Netherlands Antilles, and collected from March 1999 to March 2000 were investigated by a range of molecular typing techniques. Data obtained by pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), automated ribotyping, and sequence analysis of the short variable region of the flagellin gene (flaA) were analyzed separately and in combination. Similar groupings were obtained by all methods, with the data obtained by MLST and AFLP analysis exhibiting the highest degree of congruency. MLST identified 29 sequence types, which were assigned to 10 major clonal complexes. PFGE, AFLP analysis, and ribotyping identified 10, 9, and 8 of these clonal groups, respectively; however, these three techniques permitted subdivision of the clonal groups into more different types. Members of seven clonal groups comprising 107 isolates were obtained from November 1999 to February 2000, and no distinguishing characteristics were identified for two GBS-associated strains. The sequence type 41 (ST-41), ST-508, and ST-657 clonal complexes and their corresponding AFLP types have been rare or absent in the Campylobacter data sets described to date. We conclude that several clonal complexes of C. jejuni are associated with human disease in Cura?ao, and some of these have not been reported elsewhere. Furthermore, given the observation that C. jejuni-associated diseases appear to be more severe from November to February, it can be speculated that this may be due to the presence of virulent clones with a limited span of circulation.     

Preparation of visually cued arm movements in monkey. Involvement of inferior parietal cortex

Single-unit activity was recorded in monkey inferior parietal lobule (IPL) during performance of a visually cued limb motor task. Many neurons in the IPL modulated their activity just after the visual cue was presented, similar to the neuronal activity observed in the premotor cortex in a previous experiment. It is suggested that IPL neurons are involved in preparation of visually cued limb movement. The present results are discussed in view of a possible role for IPL and premotor cortex in processing visual information for use by the primary motor area.     

Risk factors associated with Campylobacter jejuni infections in Curaçao, Netherlands Antilles

A steady increase in the incidence of Guillain-Barré syndrome (GBS) with a seasonal preponderance, almost exclusively related to Campylobacter jejuni, and a rise in the incidence of laboratory-confirmed Campylobacter enteritis have been reported from Cura?ao, Netherlands Antilles. We therefore investigated possible risk factors associated with diarrhea due to epidemic C. jejuni. Typing by pulsed-field gel electrophoresis identified four epidemic clones which accounted for almost 60% of the infections. One hundred six cases were included in a case-control study. Infections with epidemic clones were more frequently observed in specific districts in Willemstad, the capital of Cura?ao. One of these clones caused infections during the rainy season only and was associated with the presence of a deep well around the house. Two out of three GBS-related C. jejuni isolates belonged to an epidemic clone. The observations presented point toward water as a possible source of Campylobacter infections.     

Characterization of the exposure-disease continuum in neonates of mothers exposed to carcinogens during pregnancy

The impact of maternal exposure to carcinogens during pregnancy on childhood cancer risk may be especially relevant for genetically susceptible infants. A molecular epidemiological approach, which has the potential to characterize processes between exposure and subsequent health effects in newborns by using biomarkers, is expected to provide valuable information for actually identifying such vulnerable neonates. Therefore, biomarkers of exposure (e.g. levels of cotinine and metals in cord blood), biomarkers of the biologically relevant dose (e.g. DNA and protein adducts) and biomarkers of early effects (e.g. the occurrence of somatic mutations in cord blood) have been studied in relation to birth outcomes. In this MiniReview, the most important data concerning these biomarker studies in relation to potential adverse health effects in neonates will be summarized and will be compared to the outcome of a small study population (59 mother-child pairs) in which all these biomarkers were assessed simultaneously. Overall, it can be concluded that plasma cotinine levels, macromolecule-carcinogen adduct levels and hypoxanthine phosphoribosyltransferase mutant frequencies are increased in cord blood of neonates of mothers who were exposed during pregnancy and their levels correlated with proxies of health effects, such as reduced birth weight. Moreover, DNA damage was found to be the highest in those neonates that carried risk alleles in genes that code for biotransformation enzymes. These results were confirmed in our study, which indicates that it is possible to identify a susceptible subgroup of newborns. In summary, there is a reason for profound concern of genotoxic effects in newborns of exposed mothers.