Screening for colorectal cancer--United States, 1997.
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Colorectal cancer is the second leading cause of cancer-related deaths in the United States. During 1999, approximately 129,400 new cases of colorectal cancer will be diagnosed, and 56,600 persons will die from the disease. In 1996, the U.S. Preventive Services Task Force (USPSTF) recommended the use of specific screening tests (i.e., annual fecal-occult blood testing [FOBT] and/or periodic flexible sigmoidoscopy for persons aged > or =50 years) to reduce colorectal cancer-related mortality. In 1997, the American Cancer Society and an interdisciplinary task force developed guidelines that recommend one test or a combination of several tests for colorectal cancer screening. To estimate the proportion of the U.S. population that received colorectal cancer screening tests, CDC analyzed data from the 1997 Behavioral Risk Factor Surveillance System (BRFSS) on the use of a home-administered blood stool test, or FOBT, and sigmoidoscopy/proctoscopy. This report summarizes the results of this analysis, which documents low rates of use of colorectal cancer screening tests. (+info)
Transforming growth factor beta stimulation of colorectal cancer cell lines: type II receptor bypass and changes in adhesion molecule expression.
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The type II transforming growth factor (TGF)-beta receptor gene (TGFBR2) is often mutated in nucleotide repeat sequences in colorectal cancers that are replication error positive (RER+). These mutations are thought to be selected for escape from growth inhibition by TGF-beta rather than representing bystander events because of an increased mutation rate. We investigated the role of TGFBR2 mutations in 12 colorectal cancer cell lines. Six of these were RER+, and these were shown to have homozygous TGFBR2 mutations. All cell lines then were tested for changes in proliferation in response to TGF-beta stimulation. Despite homozygous mutation of the type II TGF-beta receptor, two RER+ cell lines, Lovo and SW48, showed statistically significant growth inhibition when stimulated by TGF-beta1 in serum-free conditions. This shows that the type II TGF-beta receptor can be bypassed in certain cases to maintain growth inhibition. We next investigated whether there was any alternative mode through which TGFBR2 mutation may give a selective advantage, such as a change in adhesion molecule expression. All cell lines were stimulated with TGF-beta1 and adhesion molecules detected by ELISA. No consistent changes were identified between the RER+ and the RER- cell lines, although changes in E-cadherin, beta-catenin, and gamma-catenin were identified in individual cell lines. We conclude that (i) type II TGF-beta receptor activity can be bypassed and thus TGFBR2 mutations in RER+ cancers may, at least sometimes, be just "bystander" events and (ii) TGF-beta can affect adhesion molecule expression so that TGFBR2 mutation may give rise to a selective advantage through an effect other escape from growth inhibition. (+info)
Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion.
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This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue. (+info)
Prognostic value of p53 genetic changes in colorectal cancer.
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PURPOSE: To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND METHODS: The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments. RESULTS: Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival. CONCLUSION: Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression. (+info)
Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women.
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BACKGROUND: The remarkable similarity of lifestyle and environmental risk factors for type 2 (non-insulin-dependent) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer. We prospectively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976. METHODS: The women, who were enrolled in the Nurses' Health Study, were assessed for history of diabetes at baseline and during follow-up by use of biennial questionnaires. Self-reported diabetes was validated by information obtained from a supplemental questionnaire on symptoms and treatment and was confirmed by medical record review in a sample of the participants. Incident cases of colorectal cancer were ascertained through medical record review. All reported P values are two-sided. RESULTS: During 18 years of follow-up (201061 person-years), we documented 892 new cases of colorectal cancer. After adjustment for age, body mass index (weight in kg/height in m2), physical activity, and other covariates, relative risks (RRs) were 1.43 (95% confidence interval [CI] = 1.10-1.87; P = .009) for colorectal cancer, 1.49 (95% CI = 1.09-2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56-2.21; P = .76) for rectal cancer, 1.56 (95% CI = 1.07-2.28; P = .02) for advanced colorectal cancer, and 2.39 (95% CI = 1.46-3.92; P = .0005) for fatal colorectal cancer. CONCLUSION: Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women. (+info)
Tetrachloroethylene-contaminated drinking water in Massachusetts and the risk of colon-rectum, lung, and other cancers.
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We conducted a population-based case-control study to evaluate the relationship between cancer of the colon-rectum (n = 326), lung (n = 252), brain (n = 37), and pancreas (n = 37), and exposure to tetrachloroethylene (PCE) from public drinking water. Subjects were exposed to PCE when it leached from the vinyl lining of drinking-water distribution pipes. Relative delivered dose of PCE was estimated using a model that took into account residential location, years of residence, water flow, and pipe characteristics. Adjusted odds ratios (ORs) for lung cancer were moderately elevated among subjects whose exposure level was above the 90th percentile whether or not a latent period was assumed [ORs and 95% confidence intervals (CIs), 3.7 (1.0-11.7), 3.3 (0.6-13.4), 6.2 (1.1-31.6), and 19.3 (2.5-141.7) for 0, 5, 7, and 9 years of latency, respectively]. The adjusted ORs for colon-rectum cancer were modestly elevated among ever-exposed subjects as more years of latency were assumed [OR and CI, 1.7 (0.8-3.8) and 2.0 (0.6-5.8) for 11 and 13 years of latency, respectively]. These elevated ORs stemmed mainly from associations with rectal cancer. Adjusted ORs for rectal cancer among ever-exposed subjects were more elevated [OR and CI, 2.6 (0. 8-6.7) and 3.1 (0.7-10.9) for 11 and 13 years of latency, respectively] than were corresponding estimates for colon cancer [OR and CI, 1.3 (0.5-3.5) and 1.5 (0.3-5.8) for 11 and 13 years of latency, respectively]. These results provide evidence for an association between PCE-contaminated public drinking water and cancer of the lung and, possibly, cancer of the colon-rectum. (+info)
Determination of high mobility group I(Y) expression level in colorectal neoplasias: a potential diagnostic marker.
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High mobility group I(Y) [HMGI(Y)] proteins are architectural factors abundantly expressed during embryogenesis, and their overexpression is known to be closely associated with neoplastic transformation of cells. This study was performed to investigate whether determination of HMGI(Y) expression level could assist in (a) differential diagnosis between colorectal carcinoma, adenoma, and normal tissue and (b) determination of the prognosis of patients with colorectal cancer. To this end, HMGI(Y) expression was determined at both the protein and mRNA levels in 30 colorectal carcinomas, 26 adenomas, and 23 normal mucosa samples, and further correlations between the protein expression levels and various clinicopathological parameters, such as depth of tumor invasion, lymphatic and/or venous involvement, regional lymph node metastasis, and Dukes' stage, were determined in 30 carcinoma cases. The expression of HMGI(Y) proteins was significantly increased in carcinoma and adenoma with severe atypia compared with that in adenoma with less atypia and normal colorectal mucosa. This increase in HMGI(Y) protein expression was found to be because of an increase in its mRNA expression by RNA in situ hybridization analysis. Clinicopathological analysis revealed that the level of HMGI(Y) protein expression was significantly correlated with parameters known to be indicative of a poor prognosis in colorectal cancer patients. These findings indicate that the determination of the HMGI(Y) protein expression level could be a potential marker for the diagnosis of colorectal neoplasias and can be of great value in predicting the prognosis of patients with colorectal cancer. (+info)
A novel, orally administered nucleoside analogue, OGT 719, inhibits the liver invasive growth of a human colorectal tumor, C170HM2.
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OGT 719 is a novel p.o. bioavailable nucleoside analogue in which galactose is incorporated onto the fluoropyrimidine moiety of the cytotoxic agent 5-fluorouracil (5-FU). OGT 719 has been designed to reduce the systemic toxicity normally associated with 5-FU while retaining activity against disease localized in the liver, in which it may be preferentially localized through the asialoglycoprotein receptor (ASGP-R). We report studies confirming the activity of OGT 719 in inhibiting growth of metastatic human colorectal tumors in the liver of nude mice. The human colorectal cancer cell line C170HM2 readily forms liver metastases in vivo. Oral administration of 1500 mg/kg/day OGT 719 inhibited liver tumor burden by 95% compared with vehicle control, without any observable signs of toxicity. When the tumor burden was increased and the same OGT 719 treatment was compared with a standard clinical dose regimen of 25 mg/kg/day 5-FU/leucovorin given i.v., both treatments were equally efficacious, although 5-FU/leucovorin treatment started 7 days earlier. In contrast to 5-FU, OGT 719 is p.o. bioavailable and has a plasma half-life between 1.5 and 3 h. Several colorectal cancer cell lines express the asialoglycoprotein receptor, although no significant levels can be detected in C170HM2 cells, consistent with the observation that OGT 719 is approximately 3 log orders of magnitude less potent in vitro than 5-FU. Flux through thymidylate synthase, as measured by 3H release from [3H]dUrd, was inhibited by OGT 719 at 4 h. The notable difference in the potency of OGT 719 efficacy on C170HM2 cells in vitro and in vivo supports our model of liver-specific activation of OGT 719. As our data suggest, OGT 719 may significantly inhibit growth of metastatic colorectal tumors in the liver in vivo. This hypothesis is presently being explored in clinical trials for primary hepatocellular carcinoma and colorectal liver metastases. (+info)