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

The Reproductive Revolution

Este texto fue publicado en 2009 por The Sociological Review. Rogamos que, a efectos de divulgación, docencia y cita bibliográfica se acuda a la publicación impresa (u online de la propia revista) y la cita sea esta: MacInnes, J., Pérez Díaz, J. (2009), "The reproductive revolution" The Sociological Review 57 (2): 262-284. Su versión html puede encontrarse en esta dirección:http://www3.interscience.wiley.com/cgi-bin/fulltext/122368561/HTMLSTART Quienes estén interesados en ampliar la información sobre nuestra Teoría de la Revolución Reproductiva pueden visitar la página web siguiente: http://www.ieg.csic.es/jperez/pags/RRweb/RRweb.htm También encontrarán en este mismo repositorio otra publicación con unaexposición en castellano de las mismas ideas y publicada en la REIS bajo el título “La tercera revolución de la modernidad: la reproductiva”.We suggest that a third revolution alongside the better known economic and political ones has been vital to the rise of modernity: the reproductive revolution, comprising a historically unrepeatable shift in the efficiency of human reproduction which for the first time brought demographic security.As well as highlighting the contribution of demographic change to the rise of modernity and addressing the limitations of orthodox theories of the demographic transition, the concept of the reproductive revolution offers a better way to integrate sociology and demography. The former has tended to pay insufficient heed to sexual reproduction, individual mortality and the generational replacement of population, while the latter has undervalued its own distinctive theoretical contribution, portraying demographic change as the effect of causes lying elsewhere. We outline a theory of the reproductive revolution, review some relevant supporting empirical evidence and briefly discuss its implications both for demographic transition theory itself, and for a range of key social changes that we suggest it made possible: the decline of patriarchy and feminisation of the public sphere, the deregulation and privatisation of sexuality, family change, the rise of identity, ‘low’ fertility and ‘population ageing’.Peer reviewe

East Anglian round towers and their churches

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