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

Progression of Salmonella Enteritidis phage type 4 strains in São Paulo State, Brazil Disseminação de cepas de Salmonella Enteritidis do fagotipo 4 (PT-4) em São Paulo, Brasil

A total of 574 S. Enteritidis strains (383 from human sources and 191 from non-human sources) isolated between 1975-95, in São Paulo State, Brazil, were phagetyped. Among the strains isolated during the period of 1975-92, 80.9% of them belonged to phage type 8 (PT-8), but in 1993 strains of PT-4 accounted for 65.2% of all the S. Enteritidis isolates. In the following years, PT-4 strains accounted for 99.7% and 98.4% of phagetyped S. Enteritidis strains. The results obtained suggested that the current epidemic of S. Enteritidis in São Paulo State is clearly associated with the progression of PT-4 strains.<br>Um total de 574 cepas de Salmonella Enteritidis isoladas no período 1975-95, em São Paulo, Brasil, foram fagotipadas. Entre estas cepas, 383 eram de origem humana e 191 isoladas de materiais de origem não humana. Verificou-se que a grande maioria (80.9%) das cepas isoladas até 1992 pertencia ao fagotipo 8 (PT-8) e que cepas do fagotipo 4 (PT-4) começaram a predominar a partir de 1993. Cepas deste fagotipo corresponderam em 1993, 1994 e 1995, respectivamente, a 65.2%, 99.7% e 98.4% das amostras fagotipadas. O aumento da S. Enteritidis em São Paulo está claramente associado a disseminação de cepas PT-4