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

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 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

The influence of travel time to health facilities on stillbirths: A geospatial case-control analysis of facility-based data in Gombe, Nigeria

Access to quality emergency obstetric and newborn care (EmONC); having a skilled attendant at birth (SBA); adequate antenatal care; and efficient referral systems are considered the most effective interventions in preventing stillbirths. We determined the influence of travel time from mother’s area of residence to a tertiary health facility where women sought care on the likelihood of delivering a stillbirth. We carried out a prospective matched case-control study between 1st January 2019 and 31st December 2019 at the Federal Teaching Hospital Gombe (FTHG), Nigeria. All women who experienced a stillbirth after hospital admission during the study period were included as cases while controls were consecutive age-matched (ratio 1:1) women who experienced a live birth. We modelled travel time to health facilities. To determine how travel time to the nearest health facility and the FTHG were predictive of the likelihood of stillbirths, we fitted a conditional logistic regression model. A total of 318 women, including 159 who had stillborn babies (cases) and 159 age-matched women who had live births (controls) were included. We did not observe any significant difference in the mean travel time to the nearest government health facility for women who had experienced a stillbirth compared to those who had a live birth [9.3 mins (SD 7.3, 11.2) vs 6.9 mins (SD 5.1, 8.7) respectively, p=0.077]. However, women who experienced a stillbirth had twice the mean travel time of women who had a live birth (26.3 vs 14.5 mins) when measured from their area of residence to the FTHG where deliveries occurred. Women who lived farther than 60 minutes were 12 times more likely of having a stillborn [OR=12 (1.8, 24.3), p=0.011] compared to those who lived within 15 minutes travel time to the FTHG. We have shown for the first time, the influence of travel time to a major tertiary referral health facility on the occurrence of stillbirths in an urban city in, northeast Nigeria

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

10.1038/ncomms12675NATURE COMMUNICATIONS7

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原著和名: [記載なし]科名: = unknown採集地: タイ カオヤイ国立公園 (タイ国 カオヤイ国立公園)採集日: 1984/10/13採集者: 萩庭丈壽整理番号: JH051286国立科学博物館整理番号: TNS-VS-94871