MTHFR C677T polymorphism and anatomopathological characteristics with prognostic significance in sporadic colorectal cancer.

Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation, repair and synthesis. The MTHFR C677T polymorphism is associated with decreased risk of CRC and increased sensitivity to 5-FU treatment. The present study addressed the relationship between this polymorphism and histopathological and immunohistochemical characteristics of prognostic significance in 50 patients from the Canary Islands.

Clinicopathological analysis of factors related to colorectal tumor perforation: influence of angiogenesis.

Colorectal tumor perforation is a life-threatening complication of this disease. However, little is known about the anatomopathological factors or pathophysiologic mechanisms involved. Pathological and immunohistochemical analysis of factors related with tumoral neo-angiogenesis, which could influence tumor perforation are assessed in this study.

Metastatic lymphs nodes and lymph node ratio as predictive factors of survival in perforated and non-perforated T4 colorectal tumors.

Aims: Recently it has been hypothesized that perforation of colorectal cancer (CRC) itself is not a predictor of poor prognosis. The aim of this study was to analyze the prognostic impact, of the spontaneous perforation of the tumour, metastatic lymph nodes and lymph node ratio (LNR) after potentially curative surgery.

Methods: Retrospective analysis of oncologic outcomes of patients with T4a CRC grouped by perforated and non-perforated tumours.

Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.

Purposes: Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants.

Tumor spectrum in lynch syndrome, DNA mismatch repair system and endogenous carcinogens.

Inactivation of Mismatch Repair genes in Lynch Syndrome, caused by inherited mutations, decreases the ability to repair DNA errors throughout life. This deficit may allow the development of any tumor type. Nevertheless, the Syndrome develops a specific tumor spectrum associated with the disease.

Genealogical tree study as screening method in the Lynch syndrome prior to genetic test.

Objectives: Despite genetic advances in the study of Lynch syndrome (LS), difficulties remain in the diagnosis of the syndrome. The aim of this study was to assess the usefulness of a detailed genealogical tree as a screening method to identify Tenerife island families with a high probability of LS.

Methods: We elaborated complete genealogical trees of the families.

Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy.

Background And Aims: The enzyme MTHFR plays an important role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation, repair, and synthesis. We analyze the relationship of MTHFR C677T and A1298C polymorphisms with biological, clinicopathological, genetic and epigenetic features of tumors, and the patient outcome after treatment with 5-FU-based chemotherapy to determine the contribution of MTHFR genotypes in the risk of colorectal cancer (CRC) and in the response to therapy.

Methods: Genomic DNA of 143 Spanish sporadic CRC and 103 controls was analyzed by polymerase chain reaction/restriction fragment length polymorphism and sequencing.

A MLH1 polymorphism that increases cancer risk is associated with better outcome in sporadic colorectal cancer.

Germline mutations or the malfunctioning of postreplicative mismatch repair genes (MMR) are responsible of hereditary nonpolyposis colorectal cancer (HNPCC), and are also implied in some sporadic colorectal cancer (CRC) forms without any familial history of this disease. Besides germinal mutations and methylation, single-nucleotide polymorphisms (SNP) can predispose to nonfamilial CRC with low to moderate penetrance. In this case-control study, we analyzed three MLH1 single-nucleotide polymorphisms (exon 5: 415G-->C, rs28930073; exon 8: 655A-->G, rs1799977 and exon 16: 1852-1853AA-->GC) in 140 sporadic colorectal cancer cases and 125 healthy individuals to evaluate the relationship among CRC risk and clinicopathologic and genetic characteristics of the tumors.

Effect of COX2 -765G>C and c.3618A>G polymorphisms on the risk and survival of sporadic colorectal cancer.

Background: The COX2 gene (also known as PTGS2) encodes one of the essential cyclooxygenases for the prostanoid synthesis, and its expression is tightly regulated at both transcriptional and posttranscriptional levels. COX2 overexpression has been detected in up to 90% of colon carcinomas, and its downregulation inhibits polyp formation. Several polymorphisms located in both 5'- and 3'- flanking regions of COX2 have been described, but their functional significance and their use as prognostic indicators are still unclear.

Do MSI-L sporadic colorectal tumors develop through "mild mutator pathway"?

Background: The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain.

RIS1, a gene with trinucleotide repeats, is a target in the mutator pathway of colorectal carcinogenesis.

Microsatellite instability (MSI) due to mismatch repair system (MMR) alterations characterizes the mutator pathway implied in colorectal cancer development. In the present study, we have analyzed the gene RIS1 (Ras-induced senescence 1) in relation to loss of heterozygosity (LOH) and its frameshift mutations for an imperfect trinucleotide repeat (GCN) located at the 3'-OH end. Additionally, we have compared the status of RIS1 with a number of genetic and clinicopathological variables.

New founding mutation in MSH2 associated with hereditary nonpolyposis colorectal cancer syndrome on the Island of Tenerife.

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary syndrome with genetic heterogeneity. The disease is caused by mutations or epigenetic silencing in DNA mismatch repair genes, MLH1, MSH2, MSH6, PMS2 and MLH3, although the vast majority of cases correspond to mutations of MLH1 and MSH2. We herein describe a nucleotide change, c.

Significance of mutations in TGFBR2 and BAX in neoplastic progression and patient outcome in sporadic colorectal tumors with high-frequency microsatellite instability.

The mutator pathway implied in the development of colorectal cancer is characterized by microsatellite instability (MSI), which is determined by alterations of mismatch repair (MMR) genes. Defects in MMR genes affect repetitive DNA tracts interspersed mostly between coding sequences, and therefore it cannot be expected that they play a role during tumor progression. Genes containing repetitive sequences within their coding regions could be targets for MSI tumorigenesis, but this does not necessarily imply a causal role for the affected gene, because most are probably passenger mutations.

Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer.

Despite the fact that the mutations in K-ras codon 12 and TP53 are common abnormalities in colorectal cancer, the determination of K-ras mutation combined with TP53 gene mutation, with diagnostic and prognostic purposes is still controversial. We have analyzed K-ras and TP53 mutations in 77 sporadic colorectal adenocarcinomas by means of polymerase chain reaction and sequencing. We observed a negative correlation between both K-ras and TP53 mutations.

Genetic alterations and MSI status in primary, synchronous, and metachronous tumors in a family with hereditary nonpolyposis colorectal cancer (HNPCC).

In colorectal cancer, different levels of microsatellite instability (MSI) have been described: high-frequency MSI, low-frequency MSI, and stable microsatellites. MSI-H characterizes a unique clinical and pathologic phenotype known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC). In this case, an increased incidence of synchronous and metachronous tumors has been reported, but there are few reports with standardized criteria of MSI in HNPCC-associated tumors.