Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

BACKGROUND: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val(58 )Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort. METHODS: Mammographic density, before diagnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option. RESULTS: A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val(58 )Met polymorphism and breast density. CONCLUSION: The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer

A joint fermi-gbm and ligo/virgo analysis of compact binary mergers from the first and second gravitational-wave observing runs

We present results from offline searches of Fermi Gamma-ray Burst Monitor (GBM) data for gamma-ray transients coincident with the compact binary coalescences observed by the gravitational-wave (GW) detectors Advanced LIGO and Advanced Virgo during their first and second observing runs. In particular, we perform follow-up for both confirmed events and low significance candidates reported in the LIGO/Virgo catalog GWTC-1. We search for temporal coincidences between these GW signals and GBM-triggered gamma-ray bursts (GRBs). We also use the GBM Untargeted and Targeted subthreshold searches to find coincident gamma-rays below the onboard triggering threshold. This work implements a refined statistical approach by incorporating GW astrophysical source probabilities and GBM visibilities of LIGO/Virgo sky localizations to search for cumulative signatures of coincident subthreshold gamma-rays. All search methods recover the short gamma-ray burst GRB 170817A occurring ∼1.7 s after the binary neutron-star merger GW170817. We also present results from a new search seeking GBM counterparts to LIGO single-interferometer triggers. This search finds a candidate joint event, but given the nature of the GBM signal and localization, as well as the high joint false alarm rate of 1.1 10-6 Hz, we do not consider it an astrophysical association. We find no additional coincidences