Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Measurement of the EMC effect in light and heavy nuclei

Inclusive electron scattering from nuclear targets has been measured to extract the nuclear dependence of the inelastic cross section (σA) in Hall C at the Thomas Jefferson National Accelerator facility. Results are presented for H2, He3, He4, B9, C12, Cu63, and Au197 at an incident electron beam energy of 5.77 GeV for a range of momentum transfer from Q2 = 2 to 7 (GeV/c)2. These data improve the precision of the existing measurements of the EMC effect in the nuclear targets at large x and allow for more detailed examinations of the A dependence of the EMC effect

Measurement of the EMC effect in light and heavy nuclei

Inclusive electron scattering from nuclear targets has been measured to extract the nuclear dependence of the inelastic cross section (σA) in Hall C at the Thomas Jefferson National Accelerator facility. Results are presented for H2, He3, He4, B9, C12, Cu63, and Au197 at an incident electron beam energy of 5.77 GeV for a range of momentum transfer from Q2 = 2 to 7 (GeV/c)2. These data improve the precision of the existing measurements of the EMC effect in the nuclear targets at large x and allow for more detailed examinations of the A dependence of the EMC effect

Reproductive factors and risk of contralateral breast cancer by BRCA1 and BRCA2 mutation status: results from the WECARE study

Reproductive factors, such as early age at menarche, late age at menopause, and nulliparity are known risk factors for breast cancer. Previously, we reported these factors to be associated with risk of developing contralateral breast cancer (CBC). In this study, we evaluated the association between these factors and CBC risk among BRCA1 and BRCA2 (BRCA1/2) mutation carriers and non-carriers. The WECARE Study is a population-based multi-center case-control study of 705 women with CBC (cases) and 1,397 women with unilateral breast cancer (controls). All participants were screened for BRCA1/2 mutations and 181 carriers were identified. Conditional logistic regression models were used to evaluate associations between reproductive factors and CBC for mutation carriers and non-carriers. None of the associations between reproductive factors and CBC risk differed between mutation carriers and non-carriers. The increase in risk with younger age at menarche and decrease in risk in women with more than two full-term pregnancies seen in non-carriers were not significantly different in carriers (adjusted RRs = 1.31, 95% CI 0.65-2.65 and 0.53, 95% CI 0.19-1.51, respectively). No significant associations between the other reproductive factors and CBC risk were observed in mutation carriers or non-carriers. For two reproductive factors previously shown to be associated with CBC risk, we observed similar associations for BRCA1/2 carriers. This suggests that reproductive variables that affect CBC risk may have similar effects in mutation carriers and non-carriers

First Measurement of the EMC effect in B10 and B11

The nuclear dependence of the inclusive inelastic electron scattering cross section (the EMC effect) has been measured for the first time in B10 and B11. Previous measurements of the EMC effect in A≤12 nuclei showed an unexpected nuclear dependence; B10 and B11 were measured to explore the EMC effect in this region in more detail. Results are presented for Be9, B10, B11, and C12 at an incident beam energy of 10.6 GeV. The EMC effect in the boron isotopes was found to be similar to that for Be9 and C12, yielding almost no nuclear dependence in the EMC effect in the range A=4-12. This represents important new data supporting the hypothesis that the EMC effect depends primarily on the local nuclear environment due to the cluster structure of these nuclei