present here a fundamental insight into

present here a fundamental insight into the nature of primary varicose vein disease. They attempt to determine if the methylenetetrahydrofolate reductase polymorphisms (MTHFR C677T and A1298C) are implied in the morphology and types of complicated disease in patients with primary varicose veins. The C677T polymorphism is located in the catalytic domain of the protein, the binding site for the MTHFR co-factor Flavin ptio manufacturer dinucleotide. This polymorphism is associated with an enhancement of the thermolability of the enzyme, a reduction of the activity, an increase of plasma homocysteine concentrations, and a decreased in plasma folate (). The second MTHFR polymorphism A1298C lies in the C-terminal end of the enzyme, the S-adenosylmethionine regulatory domain, and may result in a decrease of 40% in enzyme activity of the variant genotype (). Both polymorphisms have been found to be implicated in colon cancer risk and the response to 5-FU chemotherapy, since MTHFR is implicated in the FU metabolism (). Also, these polymorphisms have been previously implicated in thrombotic disease (). Authors argued that different genetic origins may be the cause for the morphological types, trunk and perforator, of complicated and uncomplicated disease. In the study, the authors provide a hypothesis for the impact of MTHFR polymorphisms C677T and A1298C as hereditary components of primary varicose vein disease. They establish an interesting association: the axial trunk type morphology was almost exclusively associated with homozygosity (TT) or heterozygosity in C677T, while the perforator type morphology with homozygosity (CC) or heterozygosity in A1298C. Additionally, double heterozygosity CT (C677T) and AC (A1298C) are associated with the combined trunk and perforator phenotype. On the other hand, there is an increased risk of CEAP C3-6 complication from AA to CC genotype at the A1298C polymorphism.
Despite increases in our understanding of intestinal tumour biology, colorectal cancer remains a leading cause of cancer-related death worldwide. Most colorectal cancers develop from benign adenomas, presenting an opportunity for early detection and intervention prior to the onset of malignancy. For patients with early-stage tumours, five-year survival rates are high. However, as early-stage tumours are typically asymptomatic, strategies to identify at risk individuals are critical to enable early detection. Therefore, a key challenge is improving (the currently suboptimal) patient uptake to screening programmes, as well as the development of good prognostic and predictive biomarkers for cancer risk and response to treatment. In this context and because of the well-established role of prostaglandins in colorectal tumorigenesis there are an increasing number of studies evaluating the utility of circulating prostaglandins in association with cancer risk and disease progression. In this issue of , provide evidence suggesting that the measurement of circulating prostaglandins in the blood may have potential utility in identifying patients at risk of developing, or with, colorectal cancer. This is an attractive premise, as a convenient blood-based test may increase uptake amongst eligible individuals that do not presently participate in current screening procedures (such as the faecal occult blood test). Prostaglandins are well-known to cancer biologists and have attracted a lot of attention as important targets for chemoprevention (). They are generated by cyclooxygenase (COX) enzymes (COX-1 and COX-2), which are targets of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. COX-2 is known to be upregulated in a size-dependent manner in about half of colorectal adenomas and in the majority of colorectal cancers, leading to increased PGE levels (). PGE has a major influence on colorectal tumour biology (), and the chemopreventive action of NSAIDs is thought to be mediated, at least in part, by blocking PGE production. A number of studies have highlighted that PGE-M, a urinary PGE metabolite that reflects systemic PGE levels, could serve as a prognostic biomarker in colorectal, gastric, and more recently breast cancers ().