Correction to: A meta-analysis of consanguinity and breast cancer.

The original version of this article contained an author name error. Gabiella Jones has been corrected to Gabriela Jones. The original article has been corrected.

A meta-analysis of consanguinity and breast cancer.

BACKGROUND: There have been various publications stating that consanguinity both increases and decreases the risk of breast cancer. AIMS: The objective of this study was to determine the impact of consanguinity upon breast cancer. We conducted a systematic review of the literature and meta-analysis. METHODS: Eligible studies were identified on Medline and EMBASE updated to the 19 of September 2017. Studies with sufficient comparative data were included in a meta-analysis. Analyses were carried out using RevMan software. RESULTS: Three comparative studies with a total of 317 individuals with breast cancer and 1459 controls. Reviewing the literature demonstrated conflicting conclusions of the influence of consanguinity upon breast cancer. The meta-analysis showed that there were no statistically significant associations between consanguinity and breast cancer though there was a trend protection from a history of consanguinity. CONCLUSION: Though there is limited literature published on the effects of parental consanguinity, the available data does not demonstrate that it is a risk factor for breast cancer.

Effect of anticoagulation and antiplatelet therapy on incidence of endoleaks and sac size expansions after endovascular aneurysm repair.

BACKGROUND: The effects of anticoagulation or antiplatelet therapy on the incidence of endoleak and aneurysm sac size after endovascular aneurysm repair (EVAR) are unclear. This study aims to determine whether these therapies affect the incidence of endoleaks or sac size expansions after EVAR. METHODS: The case notes of 407 patients (367 men and 40 women, mean age 74.7 years) who underwent elective EVAR between January 2006 and November 2011 were reviewed for medication history and EVAR-related outcomes. RESULTS: The median follow-up period was 18 months. There were 45 (11.1%) patients on warfarin (WA), 292 (71.7%) on antiplatelet therapy (AT) (aspirin, clopidogrel, or dipyridamole modified release), and 70 (17.2%) on no anticoagulation or antiplatelet therapy (NA). During the study period, 51 (12.5%) endoleaks were documented, 8 type I (AT = 6, NA = 0, and WA = 2) and 42 type II (AT = 31, NA = 9, and WA = 2). Medication did not significantly affect the incidence of type I (P = 0.24) (based on chi-squared analysis), type II (P = 0.33), or type III (P = 0.82) endoleaks, or sac expansions (P = 0.95). CONCLUSIONS: Warfarin and antiplatelet therapies are not associated with increased incidence of postoperative endoleaks or aneurysm sac expansion after EVAR. The data in this study support safe use of anticoagulant and antiplatelet medications in patients undergoing EVAR.

Differential microRNA expression profiles in peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a clinical condition caused by an atherosclerotic process affecting the arteries of the limbs. Despite major improvements in surgical endovascular techniques, PAD is still associated with high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short noncoding RNA controlling gene expression, have emerged as major regulators of multiple biological processes. METHODS AND RESULTS: A whole-miRNA transcriptome profiling was performed in peripheral blood from an initial sample set of patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was further investigated and validated in 2 additional sample sets. Each of these 12 miRNAs exhibited good diagnostic value as evidenced by receiver operating characteristic curve analyses. Pathway enrichment analysis using predicted and validated targets identified several signaling pathways relevant to vascular disorders. Several of these pathways, including cell adhesion molecules, were confirmed by quantifying the expression level of several candidate genes regulating the initial stages of the inflammatory atherosclerotic process. The expression level of 7 of these candidate genes exhibits striking inverse correlation with that of several, if not all, of the miRNAs of the PAD-specific miRNA signature. CONCLUSIONS: These results demonstrate the potential of miRNAs for the diagnosis of PAD and provide further insight into the molecular mechanisms leading to the development of PAD, with the potential for future therapeutic targets.

Endovascular aortic aneurysm repair in patients with hostile neck anatomy.

PURPOSE: To report a systematic review and meta-analysis of outcomes following endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA) vs. those with favorable neck anatomy (FNA). METHODS: Systematic review and meta-analysis of data on EVAR in patients with HNA and FNA was performed by 2 reviewers in February 2013. An eligible study was required to have at least 50 participants and to incorporate one or more of the HNA criteria of neck length <15 mm, neck diameter >28 mm, and/or angulation >60°. Of the 24 full-length articles ultimately reviewed, 8 were excluded, resulting in 16 articles that were suitable for inclusion in the meta-analysis. The study size ranged from 55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039 patients in the HNA group. Mean follow-up ranged from 9 to 49 months. RESULTS: Analysis of the pooled data revealed a significant increase in 30-day mortality (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p<0.01), intraoperative adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30-day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8% HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria were used to define HNA. For outcomes at >30 days, the increase in secondary interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but aneurysm-related mortality, all-cause mortality, migration, and aortic rupture did not achieve statistical significance. There was no difference in rates of sac expansion. Analysis of endoleak rates revealed a significant increase in 30-day type I endoleaks (OR 2.92, 95% CI 1.61 to 5.30; p<0.001) and late type I endoleaks (OR 1.71, 95% CI 1.31 to 2.23; p<0.0001) in patients with HNA. CONCLUSION: These results suggest that performing EVAR in patients with HNA increases the technical difficulty and results in poorer short-term outcomes. The higher rates of early and late type I endoleaks, along with secondary interventions, suggest that increased monitoring should be performed in this category of patient to ensure rapid treatment.

A variant in LDLR is associated with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. METHODS AND RESULTS: A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1×10(-4) were carried through to in silico replication in 1292 AAA cases and 30,503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (LDLR) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70-0.83; P=2.08×10(-10)). CONCLUSIONS: LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.