Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome with considerable genetic and phenotypic heterogeneity, defined by the development of multiple adenomas throughout the colorectum. FAP is caused either by monoallelic mutations in the adenomatous polyposis coli gene APC, or by biallelic germline mutations of MUTYH, this latter usually presenting with milder phenotype. The aim of the present study was to characterize the genotype and phenotype of Hungarian FAP patients. Mutation screening of 87 unrelated probands from FAP families (21 of them presented as the attenuated variant of the disease, showing <100 polyps) was performed using DNA sequencing and multiplex ligation-dependent probe amplification. Twenty-four different pathogenic mutations in APC were identified in 65 patients (75 %), including nine cases (37.5 %) with large genomic alterations. Twelve of the point mutations were novel. In addition, APC-negative samples were also tested for MUTYH mutations and we were able to identify biallelic pathogenic mutations in 23 % of these cases (5/22). Correlations between the localization of APC mutations and the clinical manifestations of the disease were observed, cases with a mutation in the codon 1200–1400 region showing earlier age of disease onset (p < 0.003). There were only a few, but definitive dissimilarities between APC- and MUTYH-associated FAP in our cohort: the age at onset of polyposis was significantly delayed for biallelic MUTYH mutation carriers as compared to patients with an APC mutation. Our data represent the first comprehensive study delineating the mutation spectra of both APC and MUTYH in Hungarian FAP families, and underscore the overlap between the clinical characteristics of APC- and MUTYH-associated phenotypes, necessitating a more appropriate clinical characterization of FAP families.

Low-expression alleles in thymidylate synthase (TYMS) were associated with decreased DFS and overall survival (DFS:hazard ratio [HR] exploration 2.65 [1.40-4.65]; p = 0.004, HR validation 1.69 [1.03-2.66]; p = 0.03). A specific multifactor dimensionality reduction derived combination of dihydropyrimidine dehydrogenase and TYMS polymorphisms was associated with increased DFS (HR exploration 0.69 [0.49-0.98]; p = 0.04, HR validation 0.66 [0.45-0.95]; p = 0.03). Specific combinations of functional polymorphisms in DPYD and TYMS were demonstrated to be associated with DFS and overall survival in patients receiving adjuvant 5-FU-based treatment. Specifically high TYMS expression alleles seem to be associated with decreased DFS.

Background: Colorectal cancer is an increasing cause of death. Circulating microRNAs (miRs) could be great diagnostic and prognostic biomarkers of colorectal cancer, but further continuation of their utility is needed for their comprehensive application. Materials and Methods: Twentyseven patients with colonic cancer, 16 with rectal cancer and 12 healthy volunteers as controls, were involved in this study. and miR-29a were determined by reverse transcription polymerase chain reaction (RT-PCR) from sera of patients. Results: Expression of miR-155, miR-21 and miR-221 was significantly higher in rectal cancer than in colonic cancer. There was no difference found between those with TNM1 cancer and controls for both cancer types. miR-155, miR-34a and miR-29a were down-regulated in all patients with cancer compared to controls. We did not find any statistically significant up-regulation of miR-221 in patients with colonic cancer compared to controls. In contrast, in patients with rectal cancer, miR-221 expression was higher than in controls. Advanced stage was also linked to higher miR-221 expression compared to early stage. Slight, but statistically significant increase was observed in miR-30a expression in patients with colon cancer compared to control individuals. Conclusion: Our results partly support previous findings. Here we report on differences in the expression of circulating microRNA between colonic and rectal tumours for the first time. Colorectal tumours are becoming more and more significant 1333 This article is freely accessible online.

Early diagnosis of recurrence and metastasis of colorectal cancer following surgery of curative intent is of vital importance in terms of survival and quality of life. The consistent implementation of appropriate patient follow-up strategy is therefore essential. Debates over the methodology, evaluation and strategy of follow-up have been known for many years, and continue today. By introducing several follow-up models, the present paper offers different options featuring certain individual, national and international, conceptual and financial aspects. Colorectal cancer is an important public health concern due to its destructive nature and frequency, it is therefore essential to develop new monitoring strategies, involving new biomarkers and extensive clinical validation. Since the recurrence rate is very high in high-risk patients, the improvement of individual patient risk estimates and the utilization of a corresponding follow-up model require broad international co-operation and common practice, along with the determination of optimal levels of evidence.

We read with great interest the excellent article of Droste and colleagues on the assessment of the effect of higher cutoff levels of quantitative fecal immunochemical tests (FIT) on test positivity rate and detection rate of earlystage colorectal cancers (CRC; ref. 1). They reported that higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs.Ott o and N emeth have developed an immunochemical technique that is suitable for simultaneous analysis of 2 blood proteins-hemoglobin and albumin-in the fecal sample (2, 3). On the basis of the results of this immunochemical technique, Hungary became a pioneer in the application of FIT onto CRC pilot screening programs and this method was used effectively in pilot populationscreening projects for early identification of CRC in Hungary: in Budapest (1997Budapest ( -1998 and in Ajka (2003-2004, n ¼ 3,996; ref. 4).In the 2 Hungarian pilot projects (n ¼ 10,509), the sensitive guaiac-based fecal occult blood test was positive in 3,015 (29%) individuals. In the second phase, immunochemical testing of hemoglobin and albumin was positive in 698 (7%) individuals, 541 (76%) of whom were referred for colonoscopy and 157 (23%) were lost to follow-up. CRC was identified and confirmed histologically for 25 (5%) people; 15 of whom had early-stage disease (in situ carcinoma or Dukes stage A). One hundred twenty-six (23%) people had high-risk adenomatous polyps (4).At a 200 ng/mL cutoff level, there was a 90% sensitivity and 98% specificity of FIT test for CRC cases. Using the same cutoff level, we found a combined 53% sensitivity and 92% specificity for large (>1 cm) adenomatous polyps and cancers (controlled by colonoscopy as gold standard).In addition to its clinical benefit, the application of fecal immunochemical tests in pilot screening program for CRC proved to be cost-effective in health-economics term, which is also with remarkable importance for health insurance reimbursement, especially in middleand low-income countries (5). Disclosure of Potential Conflicts of InterestNo potential conflicts of interest were disclosed.Received March 28, 2011; accepted March 30, 2011; published online July 7, 2011