Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition.

Pathogenic Variants (PV) in major cancer predisposition genes are only identified in approximately 10% of patients with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Next Generation Sequencing (NGS) leads to the characterization of incidental variants in genes other than those known to be associated with HBOC syndrome. The aim of this study was to determine if such incidental PV were specific to a phenotype. The detection rates of HBOC-associated and incidental PV in 1812 patients who underwent genetic testing were compared with rates in control groups FLOSSIES and ExAC. The rates of incidental PV in the PALB2, ATM and CHEK2 genes were significantly increased in the HBOC group compared to controls with, respective odds ratios of 15.2 (95% CI = 5.6-47.6), 9.6 (95% CI = 4.8-19.6) and 2.7 (95% CI = 1.3-5.5). Unsupervised Hierarchical Clustering on Principle Components characterized 3 clusters: by HBOC (P = 0.01); by ExAC and FLOSSIES (P = 0.01 and 0.02 respectively); and by HBOC, ExAC and FLOSSIES (P = 0.01, 0.04 and 0.04 respectively). Interestingly, PALB2 and ATM were grouped in the same statistical cluster defined by the HBOC group, whereas CHEK2 was in a different cluster. We identified co-occurrences of PV in ATM and BRCA genes and confirmed the Manchester Scoring System as a reliable PV predictor tool for BRCA genes but not for ATM or PALB2. This study demonstrates that ATM PV, and to a lesser extent CHEK2 PV, are associated with HBOC syndrome. The co-occurrence of ATM PV with BRCA PV suggests that such ATM variants are not sufficient alone to induce cancer, supporting a multigenism hypothesis.

Deprivation, occupational hazards and perinatal outcomes in pregnant workers.

BACKGROUND: Recent global economic difficulties have widened social inequalities, but their impact on pregnant workers is not known. AIMS: To investigate the association between deprivation, exposure to occupational hazards and adverse perinatal outcomes in pregnant workers. METHODS: A cross-sectional study performed in 2014 in French occupational health services. Eligible workers were women who had worked during their pregnancy and had a medical visit by occupational health physicians (OHPs) after delivery and at the time of returning to work. Deprivation was measured using the EPICES scale (Evaluation of Precariousness and Inequalities in Health Examination Centres). Information on birth outcomes was self-reported. Occupational risks for pregnancy were assessed by OHPs. Jobs were coded by the occupational health team using standardized French nomenclature. The groups (deprivation/no deprivation) were compared using univariate (chi-squared test) and multivariate Poisson regression analyses. RESULTS: Of 1402 pregnant workers, 293 (21%) were classed as deprived. This group more frequently encountered occupational hazards, particularly for physical exposures (P < 0.001), and had a higher risk of cumulated occupational hazards of three or more for pregnancy [adjusted relative risk (RRa) = 4.2; 95% confidence interval (CI) 2.2-7.9]. Our findings suggest that deprivation and exposure to three or more occupational hazards during pregnancy cumulatively increased the risk of pre-term birth (RRa = 3.9; 95% CI 1.2-12.4). CONCLUSIONS: Our data suggest that deprived pregnant workers are an occupationally vulnerable group.

[Occupational risks during pregnancy: Feedback from occupational medical services]. / Exposition aux risques professionnels pendant la grossesse : retour de services médicaux interentreprises.

OBJECTIVES: To describe the follow-up of pregnancies at work and exposures to pregnancy occupational hazards. METHODS: A cross-sectional study was performed between January and December 2014 in occupational health services of Languedoc-Roussillon region. Eligible workers were interviewed by occupational health physicians (OHPs) after delivery and at the time of returning to work (exposure, anticipation, prevention, communication, sick leave). Occupational skill levels were classified according to the French standard classification of occupations (version 2003) from the French National Institute of Statistics. Socioeconomic deprivation was assessed using the Evaluation of Deprivation and Inequalities in Health Examination (EPICES) individual scale. RESULTS: A total of 1347 workers were recruited. The mean age was at 30.7±4.5 years. Among pregnant workers, there were 54.2% of employees, 30.7% of intermediate occupations, 10.4% of managers and, 4.7% of manual workers. Twenty-two percent of workers were classed as deprived. Also, 43.2% of workers were exposed to three or more occupational hazards during pregnancy. Only 17.7% of workers had medical visits with OHP during pregnancy and 14.7% benefited from workstation adjustments. In contrast, the level of sick leaves was high (74.2%). CONCLUSION: Our results argue for the need to follow pregnancies at work. However, the low level of prevention activities and the high level of sick leaves raise the question of the management of pregnant women at work.

[Products toxic to reproduction used in the occupational environment: Definition, risk assessment, classification]. / Produits toxiques pour la reproduction en milieu professionnel: définition, évaluation des dangers, classification.

European regulations (transcribed into French law) aimed at protecting employees from chemicals toxic to reproduction enable classification and labelling of such substances, if they are liable to cause an alteration of male or female reproductive functions or capacity, or to induce non-hereditary harmful effects on their offspring. Three categories can be used to classify these substances in two areas, namely their impairment of fertility and their effects on development. This classification is rarely based on epidemiological study results, but most often on those of experimental toxicological studies conducted by substance manufacturers. These reproduction toxicological studies are only compulsory above a certain tonnage placed on the market. The high level of this tonnage means that these tests are effectively only conducted on rare occasions. It is reckoned that there is no reproduction experimental data for over 95% of substances newly placed on the market. These products therefore appear to be reproduction non-toxic only because they have not been tested. This is a major fault in the current labelling system, which does not allow non-toxic products to be differentiated from non-tested products. The future EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) will only slightly enhance information in this area. It can be estimated that over 80% of chemical products will not be exhaustively tested for reproduction and nearly 75% will not be tested to any degree.

Psychological autopsies for equivocal deaths.

Although in use since 1958, the term "psychological autopsy" and its constituent elements have yet to achieve either consensual validation or operational standardization. This calls into question issues of content validity and reliability when psychological autopsies are used in the field. This paper argues for a clear differentiation between psychological autopsies used subsequent to suicide versus equivocal deaths and for the recognition of Equivocal Death Psychological Autopsy as a clearly distinct form of psychological autopsy with its own constituent elements and training guidelines.

[Embolic retinitis in Haemophilus parainfluenzae endocarditis]. / Rétinite embolique au cours d'une endocartite à Haemophilus parainfluenzae.

Infectious embolic retinopathy occurring secondary to a bacterial endocarditis is described in a 38-year-old woman with known aortic disease. The infectious organism was a haemophilus parainfluenzae confirmed by serial blood cultures and characterized by an embolic power equal to fungal infection. After four-weeks period of appropriate and intensive antibiotic therapy, blood cultures became negative but new emboli were observed in the fundus. This report describes ocular lesions rarely observed in endogenous bacterial retinitis. The delay between the bacterial endocarditis and the occurrence of the retinitis emphasizes the need for a long-term follow-up. Ophthalmologic examination can be acline for changing the heart valve.

High-resolution integrated map encompassing the breast cancer loss of heterozygosity region on human chromosome 16q22.1.

Loss of heterozygosity (LOH) on the long arm of human chromosome 16 is a common genetic alteration observed in both invasive ductal and invasive lobular breast carcinomas. We have generated a high-resolution integrated map encompassing the smallest region of LOH overlap within chromosome 16q22.1 (SRO2). Southern hybridization experiments using more than 140 probes resulted in the assembly of 152 bacterial large-insert clones into a 2.8-Mb contig covering SRO2. The structure of the contig was verified by long-range mapping using total human genomic DNA, and the contig orientation was determined by fluorescence in situ hybridization. A total of 68 transcripts have been identified in the map. One of the genes residing within SRO2 is the E-cadherin gene, CDH1, which has previously been shown to be mutated in lobular breast carcinomas, resulting in loss of E-cadherin expression. In most cases of ductal carcinoma, which is the major mammary cancer type, E-cadherin is normally expressed, suggesting that other genes within 16q22.1 are involved in the development of this tumor subtype. The high-resolution map presented in this study provides a valuable resource for identification of tumor suppressor genes expected to be involved in the etiology of breast carcinomas.