Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients.

Background: Aberrant Wnt signaling activation occurs commonly in colorectal carcinogenesis, leading to upregulation of many target genes. APC (adenomatous polyposis coli) is an important component of the β-catenin destruction complex, which regulates Wnt signaling, and is often mutated in colorectal cancer (CRC). In addition to mutational events, epigenetic changes arise frequently in CRC, specifically, promoter hypermethylation which silences tumor suppressor genes.

Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

Background: The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known.

Methods: We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry.

Colorectal cancer and self-reported tooth agenesis.

Background: Germline mutations in APC and AXIN2 are both associated with colon neoplasia as well as anomalous dental development. We tested the hypothesis that congenitally missing teeth may occur more commonly in individuals diagnosed with colorectal cancer than in individuals without this diagnosis.

Methods: Via a survey conducted on 1636 individuals with colorectal cancer (CRC) and 2788 individuals with no colorectal cancer from the Colon Cancer Family Registry, self-reported information on congenitally missing teeth was collected.

Career transitions in midlife: pursuing an MSW as an older student.

This study aims to increase understanding about the challenges and opportunities for graduate schools of social work to meet the educational needs of midlife and older adults. Interviews were conducted with alumni who received their MSWs when they were age 40 or older. The Alumni Office provided 170 alumni's contact information; 61 (36%) alumni were reached and 60 (98%) agreed to participate.

Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients.

Diet and lifestyle influence colorectal cancer (CRC) risk but the molecular events that mediate these effects are poorly characterized. Several dietary and lifestyle factors can modulate DNA methylation suggesting that they may influence CRC risk through epigenetic regulation of cancer-related genes. The Wnt regulatory genes DKK1 and Wnt5a are important contributors to colonic carcinogenesis and are often silenced by promoter hypermethylation in CRC; however, the dietary contributions to these events have not been explored.

Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients.

Background: In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs.

Promoter methylation of Wnt antagonists DKK1 and SFRP1 is associated with opposing tumor subtypes in two large populations of colorectal cancer patients.

Aberrant activation of canonical Wnt signaling is a hallmark event in colorectal carcinogenesis. The Dickkopf-1 (DKK1) and Secreted Frizzled Related Protein 1 (SFRP1) genes encode extracellular inhibitors of Wnt signaling that are frequently silenced by promoter hypermethylation in colorectal cancer (CRC). These methylation events have been identified as prognostic markers of patient outcome and tumor subtype in several cancers but similar roles in CRC have not been comprehensively examined.

Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer.

Background: We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability.

Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer.

ApoE single nucleotide polymorphisms (SNPs) Cys112Arg (Epsilon-4), and Arg158Cys (Epsilon-2) have been implicated in cardiovascular and Alzheimer's disease, but their role in colorectal cancer (CRC) has not been extensively studied. We investigated whether ApoE polymorphisms alone or in combination with dietary factors selectively contribute to mismatch-repair (MMR) proficient (microsatellite stable/low or MSS/L) vs deficient (microsatellite unstable or MSI-H) CRCs. We carried out a case-control study with 906 CRC cases and 911 unaffected controls to examine the associations between ApoE polymorphisms and dietary factors and assessed their contribution to MSS/L and MSI-H CRCs.

Family history of hormonal cancers and colorectal cancer risk: a case-control study conducted in Ontario.

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well-described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first-degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk.

MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer.

The most important indicator of colorectal cancer (CRC) risk is the presence of family history of the disease. Inherited genetic changes, such as single nucleotide polymorphisms, in key candidate genes may contribute to CRC risk. We investigated whether promoter polymorphisms in DNA mismatch repair (MMR) genes MSH2 and MSH6 are associated with the risk of CRC.

Accuracy of colorectal polyp self-reports: findings from the colon cancer family registry.

Introduction: Colorectal adenomas and other types of polyps are commonly used as end points or risk factors in epidemiologic studies. However, it is not known how accurately patients are able to self-report the presence or absence of adenomas following colonoscopy.

Methods: Participants in the Colon Cancer Family Registry provided self-reports of recent colorectal cancer (CRC) screening activity, and whether or not they had ever been told they had a polyp.

Visualization of the release behaviour of microcapsules.

This paper describes an experimental technique that visualizes the release behaviour that microcapsules loaded initially with a halide salt experience when immersed in aqueous media. The technique, based on the principle of silver halide photography, involves observing the effect that contact with a dilute aqueous silver nitrate solution has on individual microcapsules. Rapid precipitation of an insoluble silver halide salt on a capsule surface provides a permanent record of the location(s) on a capsule surface at which halide ion release occurs.

MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer.

Background: Although up to 30% of patients with colorectal cancer have a positive family history of colorectal neoplasia, few colorectal cancers can be explained by mutations in high-penetrance genes. We investigated whether polymorphisms in DNA mismatch repair genes are associated with the risk of colorectal cancer.

Methods: We genotyped 929 case patients and 1098 control subjects from Ontario and 430 case patients and 275 control subjects from Newfoundland and Labrador for five polymorphisms in the mismatch repair genes MLH1 and MSH2 with the fluorogenic 5' nuclease assay.

Very high incidence of familial colorectal cancer in Newfoundland: a comparison with Ontario and 13 other population-based studies.

Newfoundland has the highest rate of colorectal cancer (CRC) of any Canadian province. In order to investigate the factors, especially genetic components, responsible for CRC we established the Newfoundland Colorectal Cancer Registry. In a 5-year period we examined every case of CRC diagnosed under the age of 75 years and obtained consent from 730 cases.

p53 expression in oral precancer as a marker for malignant potential.

The potential of p53 protein expression as a marker for determining which oral precancerous lesions may transform to malignancy with time was assessed. We compared the p53 expression in archival formalin-fixed, paraffin-embedded tissues from 22 baseline biopsies of precancerous lesions that transformed to cancer in 4-25 years against that in 68 similar lesions that did not transform over the same time period. Twenty-nine percent of precancers that transformed were p53-positive at baseline, compared to 31% of the biopsies that did not transform to malignancy.

Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing.

Oral submucous fibrosis (OSF) is a high risk precancerous condition, predominantly affecting Indians. Consumption of chilli was hypothesized as an etiologic factor on the basis of ecological observations and a solitary animal experimental study. Subsequent epidemiologic studies that included case-series reports, large cross-sectional surveys, case-control studies, cohort and intervention studies have identified areca nut as the major etiologic agent.

Melanin depigmentation of the palatal mucosa in reverse smokers: a preliminary study.

The melanin pigmentation in the palate of Indian reverse smokers was histologically studied in 80 biopsies, which were compared with corresponding tissue from 49 nontobacco users. The morphology of epithelium containing melanin in its basal part was normal in smokers and nonsmokers, in contrast to areas with a local melanin depigmentation of the epithelium found in some of the reverse smokers. Here an epithelial thinning, inflammation in the underlying connective tissue, and eventually a cancer was found.

Primary prevention trial of oral cancer in india: a 10-year follow-up study.

Oral cancer is caused by chewing and smoking of tobacco. To assess the feasibility of primary prevention of oral cancer, two cohorts were studied in base-line surveys and then followed up annually for 10-yr in Ernakulam district of Kerala state. The intervention cohort consisted of 12212 tobacco users aged 15 yr and over, who were exposed to a concentrated program of education against tobacco use.

Effect on the incidence of oral submucous fibrosis of intervention in the areca nut chewing habit.

Incidence of oral submucous fibrosis was calculated from a 10-yr prospective intervention study of 12,212 individuals with a strong component of health education on tobacco and area nut chewing. Based on 11 new cases among 6341 chewers, the annual incidence was 8.0 per 100,000 among men and 29.

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut.

A case-control study to elucidate the etiology of oral submucous fibrosis was conducted in Bhavnagar, Gujarat. Sixty consecutively arriving oral submucous fibrosis patients at a dental clinic were selected as cases. An equal number of controls matched for age, sex, religion and socioeconomic status were selected from individuals who did not exhibit any oral mucosal lesion or condition.