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

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Feminism and Futurity: Revisiting Marge Piercy's Woman on the Edge of Time

This article considers the question of feminist futurity through Marge Piercy’s Woman on the Edge of Time (1976). While dominant readings of this novel have focused on its relationship to the feminist utopian genre and feminist theory from the 1970s, this essay aims to critically reframe the novel through contemporary feminist theorising on time and futurity. Drawing on recent feminist and queer theory that suggests that the future might most productively be figured through more nuanced and renewed engagements with the past, I argue that readings of Piercy’s novel that frame it only through its contemporary moment obscure the novel’s critique of singular, linear models of time. The novel represents the future through the themes of loss, mourning and haunting, which I argue resist a model of time that moves linearly from past to future and instead bring the past and future into complex relation with each other. In this regard, Piercy’s novel is read as representing a form of feminist futurity that engages with progress in time as necessarily uneven, discontinuous and fractured, speaking to contemporary demands for a feminist futurity that might require more nuanced accounts of the pas