Impact of lunch with carbohydrates differing in glycemic index on children's cognitive functioning in the late postprandial phase: a randomized crossover study.

PURPOSE: Studies about effects of lunch dietary Glycemic Index (GI) on cognition of schoolchildren are scarce. Our previous CogniDo GI study found no changes of cognition in the early postprandial phase after consumption of two rice types with medium vs. high dietary GI for lunch (i.e., 45 min after starting lunch). This study investigated whether the dietary GI of lunch has an impact on cognition of schoolchildren in the late postprandial phase, 90 min after lunch. METHODS: A randomized, 2 × 2 crossover intervention study was conducted at a comprehensive school with 5th and 6th grade students. Participants (n = 212) were randomly assigned to either sequence 1 or 2. In the first period, participants of sequence 1 received a dish with high GI rice (GI: 79), those of sequence 2 with medium GI rice (GI: 64)-in the second period, 1 week later, vice versa. Computer-based cognitive testing was performed 90 min after lunch examining tonic alertness, visual search and task switching, and working memory. Treatment effects and treatment effects adjusted for estimated lunch glycemic load (GL) were analyzed using a linear mixed model. RESULTS: The selected cognitive parameters were not affected by the GI of lunch 90 min after lunch, neither after intention-to-treat nor in the per-protocol analysis. Adjustment for GL also did not change results. CONCLUSION: The present study revealed no notable differences after the consumption of two rice types with medium vs. high dietary GI for lunch in children's cognitive function in the late postprandial phase, 90 min after lunch. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013597); date of registration: 16/04/2018, retrospectively registered.

Stroop task performance across the lifespan: High cognitive reserve in older age is associated with enhanced proactive and reactive interference control.

Susceptibility to interference increases with age but there is large inter-individual variability in interference control in older adults due to a number of biological and environmental factors. The present study aims at analyzing behavior and ERPs in a Stroop interference task with increasing difficulty in a sample of 246 young, middle-aged and healthy old participants. The old age group was divided into three subgroups based on performance scores. The results show a gradual performance reduction with increasing age and task difficulty. However, old high performers reached a performance level comparable to middle-aged subjects. The contingent negative variation (CNV) reflecting preparation and proactive task control and the target-locked P2/N2 complex associated with retrieval and implementation of S-R mappings during reactive task control were larger in the old high than low performers and similar to middle-aged or even young participants. High performance was limited to executive control tasks, while other cognitive functions were less affected. In addition, high performance was associated with higher level of education, usage of foreign languages and higher IQ. Thus, the performance differences in old age were discussed in the framework of cognitive reserve that constitutes individual differences in neural networks underlying task performance.

ERP and Behavioral Effects of Physical and Cognitive Training on Working Memory in Aging: A Randomized Controlled Study.

Working memory (WM) performance decreases with age. A promising method to improve WM is physical or cognitive training. The present randomized controlled study is aimed at evaluating the effects of different training methods on WM. A sample of 141 healthy older adults (mean age 70 years) was assigned to one of four groups: physical training, cognitive training, a social control group, and a no-contact control group. The participants trained for four months. Before and after the training, n-back task during an EEG recording was applied. The results show that cognitive training enhanced the target detection rate in the 2-back task. This was corroborated by an increased number of repeated digits in the backward digit-span test but not in other memory tests. The improvement of WM was supported by an increased P3a prior to a correct target and an increased P3b both in nontarget and target trials. No ERP effects in the physical and no-contact control groups were found, while a reduction of P3a and P3b was found in the social control group. Thus, cognitive training enhances frontal and parietal processing related to the maintenance of a stored stimulus for subsequent matching with an upcoming stimulus and increases allocation of cognitive resources. These results indicate that multidomain cognitive training may increase WM capacity and neuronal activity in older age.

[Computer based neurocognitive testing in audiology]. / Computerbasierte Testung neurokognitiver Aspekte im Rahmen der audiologischen Diagnostik.

INTRODUCTION: Due to the demographic changes neurocognition has become an important issue also in the field of hearing rehabilitation. BACKGROUND: The present study aimed to evaluate the feasibility of a neurocognitive test using computer based tasks with regard to the elderly with and without hearing loss and its practicability for the daily clinical ENT setting. PATIENTS: 171 patients of both genders with normal hearing or a profound hearing loss were enrolled in the study: 90 middleaged persons were between 50 and 64 years (57.0 ± 4.5 years) and 81 elderly persons 65 years and older (72.5 ± 5.4). METHOD: A set of computer-based neurocognitive tasks with only visual instructions covering attention, processing speed, short- and longterm memory as well as executive functions was applied. A presession under the supervision of a trained assistant was included. RESULTS: All patients were capable to complete the assessment by themselves regardless of age and hearing status, however the hearing impaired required 15 minutes more to finish the pretest and reported about a higher level of effort than normal hearing subjects (71 % versus 63 %). Interestingly 90 % of the older individuals claimed the test to fit with all ages, whereas 30 % of the middleaged participants remained skeptical (p = 0.02). CONCLUSION: The presented neurocognitive assessment might be a useful instrument which can be easily included into the daily clinical ENT. It may give important hints to the otolaryngologist in order to develop the most effective hearing rehabilitation strategy.

Cyclin K dependent regulation of Aurora B affects apoptosis and proliferation by induction of mitotic catastrophe in prostate cancer.

Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostate cancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance of Cyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells induces apoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown of Cyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate a Cyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction of mitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence-free survival in patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promising anti-cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in prostate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome and therapy response for patients with prostate cancer.

Switching of auditory attention in "cocktail-party" listening: ERP evidence of cueing effects in younger and older adults.

Verbal communication in a "cocktail-party situation" is a major challenge for the auditory system. In particular, changes in target speaker usually result in declined speech perception. Here, we investigated whether speech cues indicating a subsequent change in target speaker reduce the costs of switching in younger and older adults. We employed event-related potential (ERP) measures and a speech perception task, in which sequences of short words were simultaneously presented by four speakers. Changes in target speaker were either unpredictable or semantically cued by a word within the target stream. Cued changes resulted in a less decreased performance than uncued changes in both age groups. The ERP analysis revealed shorter latencies in the change-related N400 and late positive complex (LPC) after cued changes, suggesting an acceleration in context updating and attention switching. Thus, both younger and older listeners used semantic cues to prepare changes in speaker setting.

Lunch at school and children's cognitive functioning in the early afternoon: results from the Cognition Intervention Study Dortmund Continued (CoCo).

Studies about effects of school lunch on children's cognition are rare; two previous studies (CogniDo, CogniDo PLUS) generally found no negative effects of lunch on children's cognitive performance at the end of lunch break (i.e. 45 min after finishing lunch), but suggested potential beneficial effects for single parameters. Therefore, the present study investigated the hypothesis of potential positive effects of school lunch on cognitive performance at early afternoon (90 min after finishing lunch). A randomised, cross-over intervention trial was conducted at a comprehensive school with fifth and sixth grade students. Participants were randomised into two groups: On day 1, group 1 did not eat lunch, whereas group 2 received lunch ad libitum. On day 2 (1 week later), group 2 did not eat lunch and group 1 received lunch ad libitum. The cognitive parameters task switching, working memory updating and alertness were tested using a computerised test battery 90 min after finishing the meal. Of the 204 recruited children, fifty were excluded because of deviations from the study protocol or absence on one of the 2 test days, which resulted in 154 participants. Data showed no significant effects of lunch on task switching, working memory updating and alertness (P values between 0·07 and 0·79). The present study suggests that school lunch does not seem to have beneficial effects on children's cognitive functions regarding the conducted tests at early afternoon. Together with our previous studies, we conclude that school lunch in general has no negative effects on cognitive performance in children. However, beneficial effects seem to be restricted to a relatively short time period after eating lunch.

Long-term habitual physical activity is associated with lower distractibility in a Stroop interference task in aging: Behavioral and ERP evidence.

Aging is associated with compromised executive control functions. Several lines of evidence point to beneficial effects of physical activity on cognition which indicate that regular physical activity may counteract the age-related decline of some executive functions. Here, we investigate the effects of lifelong physical activity (about 50 years) on interference processing in two matched groups of 20 physically high active and 20 low active healthy older men using event-related potentials (ERPs). In a low interference block of the Stroop task, participants had to indicate the meaning of color-words, while color was either compatible or incompatible with the meaning. In the high interference block, participants were asked to respond according to the ink color of the word and to ignore its meaning. Physically active seniors showed faster reaction times, lower individual variability in reaction times, and higher accuracy compared to low active seniors, particularly in the high interference block. This result was confirmed in the classic paper-and-pencil version of the Stroop task showing higher interference score in the low active than high active individuals. ERPs revealed a shorter latency of the P2 and generally more negative amplitudes of the fronto-central N2 and N450 components in the high active group compared to the low active group. The amount of interference was negatively correlated with objectively measured fitness and self-reported physical activity. The positive effect of physical fitness on interference processing in the behavioral data was related to N2 and N450 amplitudes. Taken together, this suggests that seniors reporting long-term physical activity may exhibit generally enhanced activity in the frontal cortex which enables more efficient interference resolution in the Stroop task.

The ultra-slow NAT2*6A haplotype is associated with reduced higher cognitive functions in an elderly study group.

N-Acetyltransferase 2 (NAT2) genotype is associated with age-related declines in basic sensory hearing functions. However, the possible modulatory role of NAT2 for higher cognitive functions has not yet been studied. We tested auditory goal-directed behavior and attentional control in 120 NAT2 genotyped subjects (63-88 years), using an auditory distraction paradigm in which participants responded to the duration of long and short tone stimuli. We studied involuntary shifts in attention to task-irrelevant deviant stimuli and applied event-related potentials (ERPs) to examine which cognitive subprocesses are affected by NAT2 status on a neurophysiological level. Relative to the standard stimuli, deviant stimuli decreased performance in the recently described ultra-slow acetylators (NAT2*6A and *7B): The increase in error-corrected reaction times (a combined measure of response speed and accuracy) in ultra-slow acetylators (254 ms increase) was more than twice as high as in the rapid acetylator reference group (111 ms increase; p < 0.01). The increase was still higher than in the other slow acetylators (149 ms increase, p < 0.05). In addition, clear differences were found in the ERP results: Ultra-slow acetylators showed deficits specifically in the automatic detection of changes in the acoustic environment as evidenced by reduced mismatch negativity (MMN, p < 0.005 compared to rapid acetylators). Refocussing of attention after a distracting event was also impaired in the ultra-slow acetylators as evidenced by a reduced re-orienting negativity (RON, p < 0.01 compared to rapid acetylators). In conclusion, the ultra-slow acetylation status was associated with reduced higher cognitive functions.

Toxoplasma gondii impairs memory in infected seniors.

Almost 30% of humans present a Toxoplasma gondii positive antibody status and its prevalence increases with age. The central nervous system is the main target. However, little is known about the influence of asymptomatic i.e. latent Toxoplasmosis on cognitive functions in humans. To investigate neurocognitive dysfunctions in asymptomatic older adults with T. gondii positive antibody status a double-blinded neuropsychological study was conducted. The participants were classified from a population-based sample (N=131) of healthy participants with an age of 65 years and older into two groups with 42 individuals each: Toxoplasmosis positive (T-pos; IgG>50 IU/ml) and Toxoplasmosis negative (T-neg; IgG=0 IU/ml). The outcome measures were a computer-based working-memory test (2-back) and several standardized psychometric tests of memory and executive cognitive functions. T-pos seniors showed an impairment of different aspects of memory. The rate of correctly detected target symbols in a 2-back task was decreased by nearly 9% (P=0.020), corresponding to a performance reduction of about 35% in working memory relative to the T-neg group. Moreover, T-pos seniors had a lower performance in a verbal memory test, both regarding immediate recall (10% reduction; P=0.022), delayed recognition (6%; P=0.037) and recall from long-term memory assessed by the word fluency tests (12%; P=0.029). In contrast, executive functions were not affected. The effects remained mostly unchanged after controlling for medication. The impairment of memory functions in T-pos seniors was accompanied by a decreased self-reported quality of life. Because of the high prevalence of asymptomatic Toxoplasmosis and an increasing population of older adults this finding is of high relevance for public health.

A distributed theta network of error generation and processing in aging.

Based on previous concepts that a distributed theta network with a central "hub" in the medial frontal cortex is critically involved in movement regulation, monitoring, and control, the present study explored the involvement of this network in error processing with advancing age in humans. For that aim, the oscillatory neurodynamics of motor theta oscillations was analyzed at multiple cortical regions during correct and error responses in a sample of older adults. Response-related potentials (RRPs) of correct and incorrect reactions were recorded in a four-choice reaction task. RRPs were decomposed in the time-frequency domain to extract oscillatory theta activity. Motor theta oscillations at extended motor regions were analyzed with respect to power, temporal synchronization, and functional connectivity. Major results demonstrated that errors had pronounced effects on motor theta oscillations at cortical regions beyond the medial frontal cortex by being associated with (1) theta power increase in the hemisphere contra-lateral to the movement, (2) suppressed spatial and temporal synchronization at pre-motor areas contra-lateral to the responding hand, (2) inhibited connections between the medial frontal cortex and sensorimotor areas, and (3) suppressed connectivity and temporal phase-synchronization of motor theta networks in the posterior left hemisphere, irrespective of the hand, left, or right, with which the error was made. The distributed effects of errors on motor theta oscillations demonstrate that theta networks support performance monitoring. The reorganization of these networks with aging implies that in older individuals, performance monitoring is associated with a disengagement of the medial frontal region and difficulties in controlling the focus of motor attention and response selection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-10018-4.

Motor oscillations reveal new correlates of error processing in the human brain.

It has been demonstrated that during motor responses, the activation of the motor cortical regions emerges in close association with the activation of the medial frontal cortex implicated with performance monitoring and cognitive control. The present study explored the oscillatory neurodynamics of response-related potentials during correct and error responses to test the hypothesis that such continuous communication would modify the characteristics of motor potentials during performance errors. Electroencephalogram (EEG) was recorded at 64 electrodes in a four-choice reaction task and response-related potentials (RRPs) of correct and error responses were analysed. Oscillatory RRP components at extended motor areas were analysed in the theta (3.5-7 Hz) and delta (1-3 Hz) frequency bands with respect to power, temporal synchronization (phase-locking factor, PLF), and spatial synchronization (phase-locking value, PLV). Major results demonstrated that motor oscillations differed between correct and error responses. Error-related changes (1) were frequency-specific, engaging delta and theta frequency bands, (2) emerged already before response production, and (3) had specific regional topographies at posterior sensorimotor and anterior (premotor and medial frontal) areas. Specifically, the connectedness of motor and sensorimotor areas contra-lateral to the response supported by delta networks was substantially reduced during errors. Also, there was an error-related suppression of the phase stability of delta and theta oscillations at these areas. This synchronization reduction was accompanied by increased temporal synchronization of motor theta oscillations at bi-lateral premotor regions and by two distinctive error-related effects at medial frontal regions: (1) a focused fronto-central enhancement of theta power and (2) a separable enhancement of the temporal synchronization of delta oscillations with a localized medial frontal focus. Together, these observations indicate that the electrophysiological signatures of performance errors are not limited to the medial frontal signals, but they also involve the dynamics of oscillatory motor networks at extended cortical regions generating the movement. Also, they provide a more detailed picture of the medial frontal processes activated in relation to error processing.

Aging alters functional connectivity of motor theta networks during sensorimotor reactions.

OBJECTIVE: Both cognitive and primary motor networks alter with advancing age in humans. The networks activated in response to external environmental stimuli supported by theta oscillations remain less well explored. The present study aimed to characterize the effects of aging on the functional connectivity of response-related theta networks during sensorimotor tasks. METHODS: Electroencephalographic signals were recorded in young and middle-to-older age adults during three tasks performed in two modalities, auditory and visual: a simple reaction task, a Go-NoGo task, and a choice-reaction task. Response-related theta oscillations were computed. The phase-locking value (PLV) was used to analyze the spatial synchronization of primary motor and motor control theta networks. RESULTS: Performance was overall preserved in older adults. Independently of the task, aging was associated with reorganized connectivity of the contra-lateral primary motor cortex. In younger adults, it was synchronized with motor control regions (intra-hemispheric premotor/frontal and medial frontal). In older adults, it was only synchronized with intra-hemispheric sensorimotor regions. CONCLUSIONS: Motor theta networks of older adults manifest a functional decoupling between the response-generating motor cortex and motor control regions, which was not modulated by task variables. The overall preserved performance in older adults suggests that the increased connectivity within the sensorimotor network is associated with an excessive reliance on sensorimotor feedback during movement execution compensating for a deficient cognitive regulation of motor regions during sensorimotor reactions. SIGNIFICANCE: New evidence is provided for the reorganization of motor networks during sensorimotor reactions already at the transition from middle to old age.

No Impairment in Bone Turnover or Executive Functions in Well-Treated Preschoolers with Phenylketonuria-A Pilot Study.

Patients with phenylketonuria (PKU) present signs of impaired executive functioning and bone health in adolescence and adulthood, depending in part on the success of therapy in childhood. Therefore, nine children with well-treated PKU (4-7 years old, 22.2% ♀, seven with a full set of data, two included into partial analysis) and 18 age-, gender- and season-matched controls were analyzed for differences in executive functioning and bone parameters in plasma. Plasma was analyzed with commercially available kits. Cognitive performance in tonic alertness, visuo-spatial working memory, inhibitory control and task switching was assessed by a task battery presented on a touch screen. Regarding cognition, only the performance in incongruent conditions in inhibitory control was significantly better in children with PKU than in controls. No further differences in cognitive tests were detected. Furthermore, no significant difference in the bone turnover markers osteocalcin, undercarboxylated osteocalcin and CTX were detected between children with PKU and controls, while children with PKU had a significantly higher vitamin D concentration (69.44 ± 12.83 nmol/L vs. 41.87 ± 15.99 nmol/L, p < 0.001) and trended towards lower parathyroid hormone concentrations than controls (48.27 ± 15.16 pg/mL vs. 70.61 ± 30.53 pg/mL, p = 0.066). In this small group of well-treated preschoolers with PKU, no impairments in cognitive performance and bone turnover were observed, while vitamin D supplementation of amino acid supplements seems to be sufficient to achieve good vitamin D status.

BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly - evidence from auditory distraction.

Aging affects the ability to focus attention on a given task and to ignore distractors. These functions subserve response control processes for which fronto-striatal networks have been shown to play an important role. Within these networks, the brain-derived-neurotrophic-factor (BDNF), which is known to underlie aging effects, plays a pivotal role. We investigated how cognitive subprocesses constituting a cycle of distraction, orientation and refocusing of attention are affected by the functional BDNF Val66Met polymorphism using event-related potentials (ERPs) in 122 healthy elderly. Using an auditory distraction paradigm we found that the Val/Val genotype confers a disadvantage to its carriers. This disadvantage was partly compensated by intensified attentional shifting mechanisms. It could be based on response selection processes being more vulnerable against interference from distractors in this genotype group. Processes reflecting transient sensory memory processes, or the re-orientation of attention were not affected by the BDNF Val66Met polymorphism, suggesting a higher importance of BDNF for mechanisms related to response control, than stimulus processing. The results add on recent literature showing that the Met allele confers some benefit to its carriers. We suggest an account for unifying different results of BDNF Val66Met association studies in executive functions, based on the role of BDNF in fronto-striatal circuits.

Temporal dynamics of interference in Simon and Eriksen tasks considered within the context of a dual-process model.

Behavioral and brain potential measures were employed to compare interference in Eriksen and Simon tasks. Assuming a dual-process model of interference elicited in speeded response tasks, we hypothesized that only lateralized stimuli in the Simon task induce fast S-R priming via direct unconditional processes, while Eriksen interference effects are induced later via indirect conditional processes. Delays to responses for incongruent trials were indeed larger in the Eriksen than in the Simon task. Only lateralized stimuli in the Simon task elicited early S-R priming, maximal at parietal areas. Incongruent flankers in the Eriksen task elicited interference later, visible as a lateralized N2. Eriksen interference also elicited an additional component (N350), which accounted for the larger behavioral interference effects in the Eriksen task. The findings suggest that interference and its resolution involve different processes for Simon and Eriksen tasks.

Effects of cognitive and stress management training in middle-aged and older industrial workers in different socioeconomic settings: a randomized controlled study.

Introduction: The demographic change requires longer working lifetime. However, fear of job loss may lead to chronic stress whereas aging and unchallenging work may accelerate cognitive decline and early retirement. Long-time repetitive work led to impairments of cognitive functions in middle-aged and older employees, as demonstrated in a previous study conducted in a large car manufacturer. In the present study, a training concept was implemented to enhance the cognitive and emotional competence of these employees. Methods: A first group of employees received a trainer-guided cognitive training only, whereas a wait list control group received a cognitive training and stress management training. This design was applied in two independent samples separated by one year either during or after a socioeconomically tense situation of the factory. Results: In sample 1, with a tense occupational situation, the cognitive training effects occurred with a delay of three months. In contrast, in sample 2, with less critical socioeconomic situation, the training effects occurred immediately and persisted three months later. Stress management training showed reduction of subjectively and objectively measured stress level. Discussion: The results indicate that effects of cognitive interventions are diminished under chronic stress which can be reduced after a short stress management training. This leads also to enhanced attention and memory in daily life. In contrast, in Sample 2 with less chronic stress, effects of cognitive training were stronger and persisted at least three months later, whereas stress management training had less impact. This suggests that cognitive learning in occupational settings is only efficient at lower stress levels.

Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict monitoring and flexible adaptation of actions.

Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.