Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer.

We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC).

Polymorphisms of endothelial nitric oxide synthases (eNOS) have been shown to be associated with cancer susceptibility. However, the results of such studies are conflicting to date. We investigated whether polymorphisms of the eNOS gene correlated with patients with colorectal cancer (CRC), relative to healthy individuals.

We quantitated the methylated fraction of CpG sites in the promoter regions of O6-MGMT, p14ARF, p16INK4a, RASSF1A and APC1A in tumor tissue from patients with colorectal cancer (CRC) in order to determine if promoter hypermethylation of any of these genes predicts survival. DNA was isolated from 111 primary CRC and 46 matched normal colorectal mucosa samples from the same patients, obtained at primary surgery and DNA methylation was examined by Pyrosequencing®. Follow-up time was up to 20 years. Patients showed partial promoter methylation in the following frequencies: O6-MGMT, 34%; p14ARF, 29%; p16INK4a, 28%; RASSF1A, 14%; and APC1A, 27%. Normal mucosa was always unmethylated. CRC patients with methylated p14ARF gene promoter had significantly worse prognosis (p=0.036), whereas those with methylated O6-MGMT had significantly better prognosis through the first 60 months post-treatment (RR 0.36; p=0.023). Methylation of one or more of the genes from the set p14ARF, RASSF1A and APC1A, was significantly (p=0.021) associated with worse prognosis even adjusting for tumor stage and differentiation (RR 2.2, p=0.037). Thus, DNA methylation of the p14ARF, RASSF1A and APC1A genes, diagnosed by Pyrosequencing, defines a poor prognosis subset of CRC patients independently of both tumor stage and differentiation. O6-MGMT methylation may play a protective role.

The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown.

No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17-92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive.

Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.

In the CRYSTAL study adding cetuximab to first-line FOLFIRI significantly improved outcome in patients with KRAS wild-type metastatic colorectal cancer. Quality of life (QoL) was assessed, and associations with tumour response and survival were investigated.

Randomized clinical trials showed the benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or >1 cm HER2+ breast carcinomas. No efficacy data have been published on ATBC in large series of pT1abN0 HER2+ tumors.

Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives (FDR) of gastric cancer (GC) patients following H. pylori eradication.

The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact in the context of a prospective randomized trial.

NOTCH1 and SF3B1 mutations have been previously reported to have prognostic significance in chronic lymphocytic leukemia but to date they have not been validated in a prospective, controlled clinical trial. We have assessed the impact of these mutations in a cohort of 494 patients treated within the randomized phase 3 United Kingdom Leukaemia Research Fund Chronic Lymphocytic Leukemia 4 (UK LRF CCL4) trial that compared chlorambucil and fludarabine with and without cyclophosphamide in previously untreated patients. We investigated the relationship of mutations in NOTCH1 (exon 34) and SF3B1 (exon 14-16) to treatment response, survival and a panel of established biologic variables. NOTCH1 and SF3B1 mutations were found in 10% and17% of patients, respectively. NOTCH1 mutations correlated with unmutated IGHV genes, trisomy 12, high CD38/ ZAP-70 expression and were associated with reduced overall (median 54.8 vs 74.6 months, P = .02) and progression-free (median 22.0 vs 26.4 months, P = .02) survival. SF3B1 mutations were significantly associated with high CD38 expression and with shorter overall survival (median 54.3 vs 79.0 months, P < .001). Furthermore, multivariate analysis, including baseline clinical variables, treatment, and adverse prognostic factors demonstrated that although TP53 alterations remained the most informative marker of dismal survival in this cohort, NOTCH1 (HR 1.58, P = .03) and SF3B1 (HR 1.52, P = .01) mutations have added independent prognostic value.

Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC).

The cytochrome P450 2C9 enzyme (CYP2C9) is involved in metabolism of endogenous compounds, drugs, and procarcinogens. Two common nonsynonymous polymorphisms in CYP2C9 are associated with reduced enzyme activity: CYP2C9*2 (rs1799853, R144C) and CYP2C9*3 (rs1057910, I359L).

Hepatocarcinoma represents one of the most malignant cancer types. Esophageal cancer-related gene 2 (ECRG2) is found to be critical in the process of carcinogenesis. It regulates urokinase-type plasmin activator receptor and extracellular matrix function and its polymorphism in exon 4 is associated with cancer relapse. To explore new strategies to fight against cancer, here we first systematically evaluated the therapeutic potential as a biological tool using adenoviral vector (Ad-ECRG2). Ad-ECRG2 is exogenously expressed in cytoplasm and is potent to suppress the growth of cancer cell by inducing apoptosis as effective as Ad-p53. Ad-ECRG2 is able to suppress the invasion and adhesion of cancer cells at low titers. It alters the expression of a panel of cancer-related molecules, including nuclear factor-kB, matrix metalloproteinase 2 and E-cadherin, contributing to reverse malignancy phenotype of cancer cells. In vivo experiments show a significant inhibition of cancer growth by intratumoral Ad-ECRG2 administration. No evident toxicity was observed in the model animal during the study. We concluded that ECRG2 is a potential molecular target in biological therapy strategies for cancer treatment.

Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown.

Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT).

Defects in DNA repair pathways have been linked with colorectal cancer (CRC). Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation. It is known that radiation results in DNA damage directly or indirectly by radiation-induced bystander effect (RIBE) by causing double-strand breaks (DSBs). The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivo.

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.