Genetics of venous thrombosis: insights from a new genome wide association study

Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance. Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT

Colorectal Cancer Surgery: What Is Evidence Based and How Should We Do It?

Evidence-based medicine was first defined by Sackett as ‘the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients’. This requires good quality studies with a high level of proof. However, these studies are often lacking in colorectal surgery. Nevertheless, the topics on which there is general agreement will be discussed. There is now good evidence that the laparoscopic approach is at least equivalent in oncological terms to the conventional open approach in colonic surgery. The question, however, remains unanswered for rectal cancer surgery, which is technically more demanding. Although there are no randomized studies, the introduction of total mesorectal excision for rectal cancer has achieved a major reduction in local recurrence and has been adopted as the gold standard by all colorectal surgeons. Extending this concept to colonic cancer surgery is currently under discussion. The different types of reconstruction in sphincter-preserving surgery which achieve a better functional result than straight anastomosis, including colonic pouch, transverse coloplasty and side-to-end anastomosis, will be discussed. The benefit of temporary fecal diversion in low anastomosis has now been demonstrated with a good level of evidence. The technique of abdominoperineal resection has evolved in the last years and now aims at obtaining a cylindrical specimen, which has resulted in a significant reduction of the local recurrence rate. In early rectal cancer, the technique of local resection has been improved by the introduction of transanal endoscopic microsurgery.</jats:p

Questions aux professeurs Daniel Van Gansbeke et Emmanuel Tiret

SCOPUS: re.jinfo:eu-repo/semantics/publishe