Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Thiolated polymers: Stability of thiol moieties under different storage conditions

The purpose of this study was to evaluate the stability of thiolated polymers - so-called thiomers. A polycarbophil-cysteine conjugate and a chitosan-thioglycolic acid conjugate were chosen as representative anionic and cationic thiomer. The thiol group bearing compounds L-cysteine and thioglycolic acid were introduced to polycarbophil and chitosan, respectively with a coupling reaction mediated by a carbodiimide. The resulting thiolated polymers were freeze-dried and the amount of thiol groups on the thiomer was determined spectrophotometrically. Each kind of polymer was directly used or compressed into 1 mg matrix-tablets. Polymers were stored for a period of six months at four different storage conditions, namely at -20°C (56% relative humidity; RH), 4°C (53% RH), at 20°C (70% RH), and at 22°C (25% RH). Samples were taken after 6 months to determine the formation of disulfide bonds and the remaining thiol groups on the polymer. When the polycarbophil-cysteine and chitosan-thioglycolic acid conjugate were stored as powder a decrease of free thiol groups was observed only after storage at 20°C and 70% RH. Both polymers were found to be stable under all storage conditions when compressed into matrix tablets. The results provide the base for the use of thiomers as auxiliary agents in commercial products