Exposition des travailleurs en élevages de porcs et de volailles de chair à l’ammoniac et aux particules

The air of pig and poultry farms contains ammonia and dust. To characterize the exposure of workers to these pollutants, data were collected on farms. Measurements were carried out in 20 pig farms during piglet care, weaning, feeding of piglets and sorting pigs and in 21 poultry farms during inspection of animals, catching birds, the manure disposal and litter distribution in the building. In general, particulate matter and ammonia are not considered as occupational hazards by workers. The risk is often minimized but measurements showed that exposure to particulate matter and ammonia poses a risk to their health (increased respiratory symptoms and decreased respiratory capacity). In addition, 15% of pig farms had an ammonia content above the occupational exposure limit (20 ppm for 15 minutes) on at least one of the tasks monitored. In poultry farming, 17% of the ammonia measurements during the tasks followed without mulching, and 3% of all the measurements of particles carried out exceeded the maximum recommended value (5 mg / m3 of cellular particles). It is necessary to sensitize the actors of the field on the respiratory risks. For this purpose, an AIR Eleveur YouTube channel was created as well as 2 brochures (protection equipment and AIR Eleveur results).L'air des bâtiments porcins et avicoles contient de l’ammoniac et des particules. Pour caractériser l'exposition des travailleurs à ces polluants, des données ont été collectées dans des exploitations agricoles. Les mesures ont été effectuées dans 20 exploitations porcines pendant des tâches considérées comme exposantes : les soins aux porcelets, le sevrage, l'alimentation des porcelets et le tri des porcs. 21 exploitations avicoles ont également été suivies pendant la surveillance en fin de bande, le ramassage, le curage du fumier et le paillage du bâtiment. En général, les particules et l'ammoniac ne sont pas considérés comme des risques professionnels par les travailleurs. Le risque est souvent minimisé mais les mesures montrent que l'exposition aux particules et à l'ammoniac impacte leur santé (augmentation des symptômes respiratoires et diminution de la capacité respiratoire). En outre, 15% des exploitations porcines ont une teneur en ammoniac supérieure à la limite d'exposition professionnelle (20 ppm pendant 15 minutes) pour au moins une des tâches contrôlées. En aviculture, 17% des mesures d'ammoniac au cours des tâches suivies sans paillage et 3% de toutes les mesures de particules effectuées dépassent la valeur maximale recommandée (5 mg/m3 de particules alvéolaires). Il est nécessaire de sensibiliser les acteurs du terrain aux risques respiratoires. À cette fin, une chaîne YouTube AIR Eleveur a été créée, ainsi que 2 brochures (équipement de protection et résultats AIR Eleveur)

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

Exposition des travailleurs en élevages de porcs et de volailles de chair à l’ammoniac et aux particules

L'air des bâtiments porcins et avicoles contient de l’ammoniac et des particules. Pour caractériser l'exposition des travailleurs à ces polluants, des données ont été collectées dans des exploitations agricoles. Les mesures ont été effectuées dans 20 exploitations porcines pendant des tâches considérées comme exposantes : les soins aux porcelets, le sevrage, l'alimentation des porcelets et le tri des porcs. 21 exploitations avicoles ont également été suivies pendant la surveillance en fin de bande, le ramassage, le curage du fumier et le paillage du bâtiment. En général, les particules et l'ammoniac ne sont pas considérés comme des risques professionnels par les travailleurs. Le risque est souvent minimisé mais les mesures montrent que l'exposition aux particules et à l'ammoniac impacte leur santé (augmentation des symptômes respiratoires et diminution de la capacité respiratoire). En outre, 15% des exploitations porcines ont une teneur en ammoniac supérieure à la limite d'exposition professionnelle (20 ppm pendant 15 minutes) pour au moins une des tâches contrôlées. En aviculture, 17% des mesures d'ammoniac au cours des tâches suivies sans paillage et 3% de toutes les mesures de particules effectuées dépassent la valeur maximale recommandée (5 mg/m3 de particules alvéolaires). Il est nécessaire de sensibiliser les acteurs du terrain aux risques respiratoires. À cette fin, une chaîne YouTube AIR Eleveur a été créée, ainsi que 2 brochures (équipement de protection et résultats AIR Eleveur).The air of pig and poultry farms contains ammonia and dust. To characterize the exposure of workers to these pollutants, data were collected on farms. Measurements were carried out in 20 pig farms during piglet care, weaning, feeding of piglets and sorting pigs and in 21 poultry farms during inspection of animals, catching birds, the manure disposal and litter distribution in the building. In general, particulate matter and ammonia are not considered as occupational hazards by workers. The risk is often minimized but measurements showed that exposure to particulate matter and ammonia poses a risk to their health (increased respiratory symptoms and decreased respiratory capacity). In addition, 15% of pig farms had an ammonia content above the occupational exposure limit (20 ppm for 15 minutes) on at least one of the tasks monitored. In poultry farming, 17% of the ammonia measurements during the tasks followed without mulching, and 3% of all the measurements of particles carried out exceeded the maximum recommended value (5 mg / m3 of cellular particles). It is necessary to sensitize the actors of the field on the respiratory risks. For this purpose, an AIR Eleveur YouTube channel was created as well as 2 brochures (protection equipment and AIR Eleveur results)