Luc Fontana

Psychopathological features of a patient population of targets of workplace bullying

BACKGROUND A strong association between workplace bullying and subsequent anxiety and depression, indicated by empirical research, suggests that bullying is an aetiological factor for mental health problems. AIMS To evaluate levels of stress and anxiety-depression disorder developed by targets of workplace bullying together with outcome at 12 months and to characterize this population in terms of psychopathology and sociodemographic features. METHODS Forty-eight patients (36 women and 12 men) meeting Leymann Inventory of Psychological Terror criteria for bullying were included in a prospective study. Evaluations were performed at first consultation and at 12 months using a standard clinical interview, a visual analogue scale of stress, the Hospital Anxiety and Depression (HAD) scale, the Beech scale of stress in the workplace and a projective test (Picture-Frustration Study). RESULTS At first consultation, 81% of patients showed high levels of perceived stress at work and 83 and 52% presented with anxiety or depression, respectively. At 12 months, only 19% of working patients expressed a feeling of stress at work. There was a significant change in symptoms of anxiety while there was no change in symptoms of depression. Stress at work and depression influenced significatively capacity to go back to work. At 12-month assessments, workers showed a significantly better score on the HAD scale than non-workers. Over half the targets presented a neuroticism-related predominant personality trait. CONCLUSION Workplace bullying can have severe mental health repercussions, triggering serious and persistent underlying disorders.

Gene Expression Profiling of Breast Cancer Cell Lines in Response to Soy Isoflavones Using a Pangenomic Microarray Approach

Although the rate of breast cancer differs between women in Asian and Western countries, molecular genetics/genomics basis of this epidemiological observation remains elusive. Moreover, the intake of phytoestrogens is associated with a lower incidence of breast cancer. Genistein and daidzein are the primary soy isoflavones with a chemical structure similar to estrogens. Conceivably, the actions of phytoestrogens on gene expression signatures might mediate their postulated effects on breast cancer pathogenesis. The present study evaluated the transcriptional responsiveness of breast cancer cells to soy phytoestrogens using a whole-genome microarray-based approach. Human breast cancer cell lines and a fibrocystic breast cell line were treated with genistein or daidzein. We identified 278 and 334 differentially expressed genes after genistein or daidzein treatment, respectively, in estrogen-positive (MCF-7) and estrogen-negative (MDA-MB-231, MCF-10a) cells. Hierarchical clustering of this finding revealed a significant modulation, respectively, of 246 or 169 genes after genistein or daidzein exposures. Importantly, the molecular pathways for the differentially expressed genes included those that relate to cell communication, biodegradation of xenobiotics, lipid metabolism, signal transduction, and cell growth/death. These molecular observations collectively contribute to a growing knowledgebase on the putative mechanism(s) of action of phytoestrogens in breast cancer pathogenesis and chemoprevention.

DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk

Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes, i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair gene ERCC2 were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman® method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) > 0.85 for Asn homozygous for ERCC2 312.

Expression analyses of nuclear receptor genes in breast cancer cell lines exposed to soy phytoestrogens after BRCA2 knockdown by TaqMan Low-Density Array (TLDA)

Background Most of breast cancers are considered sporadic and modulation of the two major genes BRCA1 and BRCA2 expressions caused by tissue-specific somatic mutations lead to this pathology. The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer and investigation of their potential as anticancer agents has increased. However, the possible mechanisms and signalling pathways of phytoestrogen action in breast cancer prevention remains unknown. Results Using Taqman Low Density Array technology, we investigated the BRCA2 loss of function role in sporadic breast cancers and the links existing with soy isoflavones on a panel of nuclear receptor expression. Human breast cell lines (MCF-7, MDA-MB-231, and MCF-10a) were transfected by BRCA2-siRNA and treated with genistein (18.5 μM) or daidzein (78.5 μM) for 72 h. Generating the transitory knockdown of BRCA2 oncosuppressor, we observed different modulations in several nuclear receptor genes such as ER, RAR and RXR, as well as PPARs and VDR according to the studied breast cell line. Additional isoflavone treatments showed different nuclear receptor gene modulation profiles. Conclusion Our results seemed to implicate the oncosuppressor BRCA2 and the phytoestrogen pathways in different nuclear gene expressions via an ER-independent manner.

Gene signature of rat mammary glands: Influence of lifelong soy isoflavones consumption.

Epidemiological studies have indicated that phytoestrogen has a preventive effect on breast cancer development. However, controversial results have been reported suggesting these compounds have ambivalent effects on breast tissue. Here, we report a transgenerational study conducted on female Wistar rats fed a diet enriched with phytoestrogen. Using a pangenomic microarray approach, a transcriptomic study was performed on mammary glands extracted from the animals. Gene expression was examined at 3 ages: 3, 18 and 24 months. The F1 generation did not express the same genes as the F0 control generation fed the same diet. This effect increased with animal age: in 3-, 18- and 24-month-old rats, 293, 441 and 2868 differentially expressed genes were respectively observed. These results suggest that long-term exposure to isoflavones may play a key role in gene regulation. Additionally, epigenetic patterns were found to be affected by DNA-methyltransferase and histone-deacetylase expression.

Report of three cases of renal oncocytoma in the same French chemical industrial factory.

To the Editor: Renal oncocytoma is a rare benign tumor, accounting for 3% to 7% of primary renal tumors. There are no clearly established etiological factors. Three cases of renal oncocytoma detected between 2000 and 2008 in employees or subcontractors working for the same factory “F” in central France during a systematic screening campaign by ultrasonography are reported. The company specializes in vitamin and amino acid synthesis, in particular, vitamin A, vitamin E, and methionine. The factory is currently undergoing epidemiological investigations by the National Health and Work Department of the National Health Watch Institute (InVS) following nine cases of renal cell carcinoma (RCC) detected in workers between 1994 and 2002, at first by chance and later by systematic ultrasonography. The company began systematic screening for hepatic angiosarcoma in 1986 by yearly abdominal ultrasonography of employees exposed to monomer vinyl chloride (MVC). In 1992, the screening program was extended to workers exposed to chloracetal C5. This molecule is an intermediate chemical produced in the course of a new process for vitamin A synthesis called NAVAS (new vitamin A synthesis) first implemented in the factory in 1982. At that time, the molecule was known to be mutagenic in vitro. Since 2002, all company employees undergo ultrasound screening on a voluntary basis. To date, 28 cases of RCC have been detected in this company; most were clear-cell and papillary RCC, but there were also three cases of oncocytoma and one angiomyolipoma. We describe the cases of oncocytoma with particular focus on the possible relation to occupational exposure.