Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients.

Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas. In particular, variants Y165C and G382D have been shown to play a role in Caucasian patients. To evaluate the contribution of MYH mutations to colorectal cancer burden on the population level, and to examine the MYH-associated phenotype in an unselected series of colorectal cancer patients, we determined the frequencies of Y165C and G382D MYH mutations in a population-based series of 1042 Finnish colorectal cancer patients. Four (0.4%) patients had both MYH alleles mutated. Although all these patients had multiple adenomatous polyps, the phenotypes tended to be less extreme than in previous studies on selected cases. The lowest number of colorectal adenomas at the time of cancer diagnosis was five. Cases with one mutant MYH allele were subjected to sequencing of all exons to detect possible Finnish founder mutations, but no additional changes were detected. The Y165C and G382D variants were not present in 424 Finnish cancer-free controls showing that MYH mutations are not enriched in the population. As evaluated against national Finnish Polyposis Registry data MYH-associated colorectal cancer appears to be as common as colorectal cancer associated with familial adenomatous polyposis

Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression

Abstract Background & Aims: Alterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N‐methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non‐alcoholic steatohepatitis (NASH) remains unclear. Methods: Serum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6 ± 10 (mean ± SD) years, BMI 43.3 ± 6 kg/m2, 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N‐methyltransferase (GNMT) was analysed. Results: Liver PC content was lower in those with NASH (P = 1.8 x 10−6) while serum PC levels did not differ between individuals with NASH and normal liver (P = 0.591). Interestingly, serum and liver PC did not correlate (rs = −0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (rs = 0.866, P = 7.1 x 10−49), while liver PC content did not correlate with serum cholesterol (rs = 0.065, P = 0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P = 3.8 x 10−4) and correlated with liver PC content (rs = 0.265, P = 0.001). Conclusions: Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression

Supplement to the article: Aging of the population may not lead to an increase in the numbers of acute coronary events: a community surveillance study and modelled forecast to the future

The zip file contains the C++ source files for the programme used in the article and an example (in R programming language) on how to use the programme. Precompiled versions of the programme are included as Windows-32bit .dll (works also on the 32-bit version of R) and Linux 64 bit .so libraries. Please read the "readme.txt" file firs