Introduction Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of ...large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies. Methods We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Results SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P < 0.05). Notably, the minor alleles of two SNPs (rs7166081 and rs3825977) in high linkage disequilibrium (r.sup.2 = 0.77), located at the SMAD3 locus (15q22), were each associated with increased breast cancer risk for BRCA2 mutation carriers (relative risk = 1.25, 95% confidence interval = 1.07 to 1.45, P.sub.trend = 0.004; and relative risk = 1.20, 95% confidence interval = 1.03 to 1.40, P.sub.trend = 0.018). Conclusions This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations.
Psychological and physiological stress responses of 36 male and 29 female assembly workers were examined during and after work at a car engine factory. Two different ways of organizing assembly work ...were compared: one with a traditional assembly line and another with a more flexible work organization. As expected, both male and female workers in the flexible organization reported significantly more variation, independence and abilities to learn new skills at work. Workers in both forms of work organization showed a significant increase in urinary epinephrine and norepinephrine during work compared to the work-free day at home. Males had significantly higher epinephrine and systolic blood pressure levels than females. Other results of the studies are discussed.
Two contrasting 90 min VDT work situations were simulated in the laboratory: (1) a machine-paced, repetitive data entry task; and (2) a stimulating, self-paced learning task with successive feedback. ...Thirty non-smoking male students (20-34 years), without previous experience of VDT work, participated individually in each condition on two consecutive days (balanced order) and in a task-free baseline condition. Self-reports and successive measurements (ambulatory recordings) of systolic and diastolic blood pressure and heart rate were obtained during work and during a subsequent 60 min period of deactivation. Urine samples were obtained after each period for the determination of catecholamines and cortisol. In the baseline condition, measurements were obtained at corresponding times of the day. As expected, the data entry task was associated with self-reports of boredom, irritation, and unpleasantness; the learning task wtih alertness, interest, and ability to concentrate. Similar elevations of physiological measurements occurred in both work situations. However, differences between conditions were found after work. Following data entry, deactivation was slower in five of the six variables (significant for epinephrine).
Urinary catecholamines and cortisol were measured in healthy nonsmoking white collar workers (14 male and 15 female managers, 15 male and 14 female clerical workers), aged 30-50 years, during a ...one-hour period of laboratory-induced stress comprising five tests and a Type A interview, and during a subsequent period of rest in the laboratory. Values were compared with data obtained four months earlier from the same subjects during a normal day at work (4 values) and during a work-free day at home (4 values). No significant group differences were found during rest in the laboratory. However, during laboratory-induced stress, female managers had the highest norepinephrine values, which contributed to significantly (p less than 0.01) higher values in women than in men. Correlations between absolute measurements from laboratory and naturalistic conditions were generally positive and reached significance in most cases. Correlations between reactivity measurements in the laboratory and at work (change from rest to stress and from home to work, respectively) were generally low, whereas correlations between reactivity at different times of the day were relatively high. The data suggest that generalizability of neuroendocrine reactivity from laboratory stress to real-life stress is low. However, in agreement with earlier experimental findings, absolute levels of catecholamine and cortisol excretion were consistent over conditions and time.
The MyoElectric (ME) activity from the trapezius muscle in 24 female supermarket employees doing cash register work were evaluated and compared to department work in the supermarket. The result shows ...that the cash register work typically is of a more static nature than the other tasks tested. Contrary to what was anticipated there were no major difference in the subject's ability to find muscle rest when doing work at the various departments at the supermarket compared to working at the cash register, however large individual differences were observed. The results indicates, that by introducing job rotation, where the cash register work is mixed with other work in the supermarket, the cashiers may be able to break the long-standing static activation of the neck and shoulder region and possibly prevent neck and shoulder pain to develop.
Thirty healthy nonsmoking men and 30 women underwent a laboratory reactivity assessment with systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) recorded at rest and during ...behavioral (mirror image tracing, mental arithmetic, color word conflict task and a semistructured Type A interview), and physical tasks (isometric exercise and the cold pressor test). Casual SBP and DBP were measured in a physician's clinic. Four months earlier SBP, DBP and HR had been monitored during a day at work and a day at home. Readings obtained in the clinic, at rest and during stress in the laboratory were related to real-life levels, reactivity (work—home difference) and variability.
For men level of cardiovascular activation at rest and during all stressors in the laboratory correlated with levels at work and at home. The best laboratory/real-life relation was observed for SBP. Systolic blood pressure levels during stress correlated with the work—home difference. Systolic blood pressure reactivity (laboratory stress levels—rest levels) to most behavioral tasks correlated with SBP levels at work and home. Daily variability and reactivity correlated with SBP reactivity to mental arithmetic and the color word conflict task. For women, levels of SBP and HR at rest and during all stressors correlated with SBP and HR at work and at home. The best laboratory/real-life relation for women was observed for HR reactivity. Casual BP in the clinic correlated with work blood pressure but generally not with daily reactivity or variability.
We conclude that BP and HR levels measured in the laboratory generalizes to real life BP and HR in both men and women and also to real life SBP reactivity in men. Laboratory induced SBP reactivity also shows a weak relation to real life SBP levels, variability and reactivity in men.
In an attempt to determine some of the structural features in position 1 that account for antivasopressor activity, eight new 1-(beta, beta-dialkyl-substituted) analogues of 1-(3-mercaptopropanoic ...acid)-8-arginine-vasopressin and 1-(3-mercaptopropanoic acid)-2-O-methyltyrosine-8-arginine-vasopressin have been designed and synthesized. The protected precursors required for these peptides were obtained by a combination of solid-phase and solutions methods. Some of the reported analogues, namely 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin, 1-(1-mercapto-4-methylcyclohexaneacetic acid)-2-O-methyltryosine-8-arginine-vasopressin, 1-(4-tert-butyl-1-mercaptocyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-8-arginine-vasopressin and 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, are among the most potent and selective antagonists of the vasopressor response to arginine-vasopressin reported to date.
Sixty healthy non-smoking white collar employees, aged 30-50, from a large corporation in Sweden participated in the study. There were four groups: 15 male and 15 female middle managers, 15 male and ...15 female clerical workers. Each participant was examined individually with regard to cardiovascular and neuroendocrine functions and self-reports for 12 consecutive hours under each of two conditions: (1) a normal day at work (9 a.m.-- 5 p.m.) and after work (6-9 p.m.), and (2) for the same time period during work-free conditions at home. In addition, everyone was given a videotaped type A-interview and a general health check-up including blood-lipid determination. Attitudes towards work, total workload (including responsibilities outside the paid work) and sex role identity were examined by questionnaires. As expected, all groups showed a moderate increase in cardiovascular and neuroendocrine activity during the day at work. After work, however, interesting group differences emerged, suggesting slower unwinding in female managers. Differences related to occupational level and/or sex were found for autonomy and social support at work, competitiveness, sex role and reported conflict between demands from paid work and other responsibilities. The stress profile of the female managers was considered in terms of possible long-term health risks.
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