Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg  = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases

A method for coronary artery calcium scoring using contrast-enhanced computed tomography

Background: Limitations to the coronary calcium score include its requirement for noncontrast imaging and radiation exposure that approaches current methods for contrast-enhanced CT angiography. Objectives: We sought to derive and validate a method of measuring the coronary artery calcium score (CACS) from standard contrast-enhanced CT, obviating the need for a second non-contrast calcium scan. Methods: The volume of intramural calcium of >320 HU in major coronary vessels was measured in 90 contrast-enhanced and traditional non-contrast calcium scan pairs. An empiric conversion factor was derived to convert the small voxel contrast-enhanced calcium volume to an Agatston calcium score. The accuracy of this technique was then prospectively validated in 120 consecutive patients undergoing clinical calcium scans and contrasted-enhanced coronary CT. Eleven patients were excluded from analysis because of the prespecified criteria of excessive noise in the contrast-enhanced CT or total coronary artery occlusion. Results: The Pearson correlation of the contrast scan-derived calcium score with the measured CACS was r 2 = 0.99. With standard CACS risk bands, agreement of the contrast-enhanced calcium score estimate with the measured CAC by quadratic weighted κ was 0.96. The 95% limits of agreement (Agatston units) were given by ±(3.2+0.14×CACS+4.44CACS). Inter-observer and intra-observer reliability with the intraclass correlation was 0.99. Conclusion: The calcium score can be accurately measured from contrast-enhanced cardiac CT scans with the use of a Hounsfield unit threshold of 320. © 2012