| 1. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- 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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| 2. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 3. |
- Cardeña, Etzel, et al.
(author)
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Letter to the editor.
- 2007
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In: Monitor on Psychology. - : SAGE Publications. - 1529-4978. ; 44:4, s. 456-457
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Journal article (peer-reviewed)
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| 4. |
- Figueroa, Alvaro A, et al.
(author)
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Long-term skeletal stability after maxillary advancement with distraction osteogenesis using a rigid external distraction device in cleft maxillary deformities.
- 2004
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In: Plastic and reconstructive surgery. - 1529-4242. ; 114:6
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Journal article (peer-reviewed)abstract
- Rigid external distraction is a highly effective technique for correction of maxillary hypoplasia in patients with orofacial clefts. The clinical results after correction of sagittal maxillary deformities in both the adult and pediatric age groups have been stable. The purpose of this retrospective longitudinal cephalometric study was to review the long-term stability of the repositioned maxilla in cleft patients who underwent maxillary advancement with rigid external distraction. Between April 1, 1995, and April 1, 1999, 17 consecutive patients with cleft maxillary hypoplasia underwent maxillary advancement using rigid external distraction. There were 13 male patients and four female patients, with ages ranging from 5.2 to 23.6 years (mean, 12.6 years). After a modified complete high Le Fort I osteotomy and a latency period of 3 to 5 days, patients underwent maxillary advancement with rigid external distraction until proper facial convexity and dental overjet and overbite were obtained. After active distraction, a 3- to 4-week period of rigid retention was undertaken; this was followed by removable elastic retention for 6 to 8 weeks using, during sleep time, an orthodontic protraction face mask. Cephalometric radiographs were obtained preoperatively, after distraction, at 1 year after distraction, and 2 or more years after distraction. The mean follow-up was 3.3 years (minimum, 2.1 years; maximum, 5.3 years). The following measurements were obtained in each cephalogram: three linear horizontal and two linear vertical maxillary measurements, two angular craniomaxillary measurements, and one craniomandibular measurement. Differences between the preoperative and postoperative cephalometric values were analyzed by paired t tests (p < 0.05). The cephalometric analysis demonstrated postoperatively significant advancement of the maxilla. In addition, the mandibular plane angle opened 1.2 degrees after surgery. After the 1- to 3-year follow-up period, the maxilla was stable in the sagittal plane. Minimal anteroposterior growth was observed in the maxilla compared with that exhibited in the anterior cranial base. However, there was significant vertical maxillary growth over the 3-year observation period. The mandibular plane angle tended to decrease during the follow-up period. The cephalometric data from this study support the clinical impression of maxillary stability after maxillary advancement with rigid external distraction in cleft patients. This effective and stable technique is now considered for all pediatric patients with severe cleft maxillary hypoplasia and for adolescent and adult patients with moderate to severe deformities.
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