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PubMed2004

No germline mutations in the histone acetyltransferase gene EP300 in BRCA1 and BRCA2 negative families with breast cancer and gastric, pancreatic, or colorectal cancer.

INTRODUCTION: Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for many, but not all, multiple-case breast and ovarian cancer families. The histone acetyltransferase gene EP300 may function as a tumour suppressor gene because it is sometimes somatically mutated in breast, colorectal, gastric and pancreatic cancers, and is located on a region of chromosome 22 that frequently undergoes loss of heterozygosity in many cancer types. We hypothesized that germline mutations in EP300 may account for some breast cancer families that include cases of gastric, pancreatic and/or colorectal cancer. METHODS: We screened the entire coding region of EP300 for mutations in the youngest affected members of 23 non-BRCA1/BRCA2 breast cancer families with at least one confirmed case of gastric, pancreatic and/or colorectal cancer. These families were ascertained in Australia through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. RESULTS: Denaturing HPLC analysis identified a heterozygous alteration at codon 211, specifically a GGC to AGC (glycine to serine) alteration, in two individuals. This conservative amino acid change was not within any known functional domains of EP300. The frequency of the Ser211 variant did not differ significantly between a series of 352 breast cancer patients (4.0%) and 254 control individuals (2.8%; P = 0.5). CONCLUSION: The present study does not support a major role for EP300 mutations in breast and ovarian cancer families with a history of gastric, pancreatic and/or colorectal cancer.

Acetyltransferases↗

PubMedDate not supplied

Colorectal cancer imaging.

Official estimates rank colorectal cancer third in both incidence and cause of death for all U.S. cancers. This article discusses the role of diagnostic imaging in screening, diagnosis and treatment of cancers of the colon and rectum. After completing this article, readers should be able to: Explain basic anatomy of the colon and rectum. Discuss the histology and staging of colorectal cancer. Identify various colorectal screening tests, including colonoscopy, computed tomography (CT) colonography and magnetic resonance (MR) colonography. Understand the role of diagnostic imaging in the diagnosis and staging of colorectal cancer. Describe diagnostic imaging of colorectal cancer recurrence.

Colonography, Computed Tomographic↗

PubMed1998

Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations.

BACKGROUND: Predisposition genetic testing is now possible for many hereditary cancer syndromes, including hereditary nonpolyposis colorectal cancer. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. OBJECTIVE: To assess the life expectancy and quality-adjusted life expectancy benefits derived from endoscopic surveillance and prophylactic colectomy for persons who carry a mutation associated with hereditary nonpolyposis colorectal cancer. DESIGN: Decision analysis model. Lifetime risk for colorectal cancer, efficacy of surveillance and colectomy, stage-specific colorectal cancer mortality, and quality of life were included in the model. SETTING: Decision about a cancer prevention strategy at the time of a positive result on genetic testing. PATIENTS: Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age. INTERVENTIONS: Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis. MEASUREMENTS: Life expectancy and quality-adjusted life expectancy. RESULTS: All risk-reduction strategies led to large gains in life expectancy for carriers of a mutation for hereditary nonpolyposis colorectal cancer, with benefits ranging from 13.5 years for surveillance to 15.6 years for prophylactic proctocolectomy at 25 years of age compared with no intervention. The benefits of colectomy compared with surveillance decreased with increasing age and were minimal if colectomy was performed at the time of colorectal cancer diagnosis. When health-related quality of life was considered, surveillance led to the greatest quality-adjusted life expectancy benefit (3.1 years compared with proctocolectomy and 0.3 years compared with subtotal colectomy). CONCLUSIONS: Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation for hereditary nonpolyposis colorectal cancer. The individual patient's choice between prophylactic surgery and surveillance is a complex decision in which personal preferences weigh heavily.

Adult↗

PubMed2025

Long non-coding RNA NEAT1 promotes colorectal cancer progression via interacting with SIRT1.

Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA, is found to be significantly dysregulated in different types of cancer, including colorectal cancer (CRC). Nevertheless, there is still much to learn about the precise functions and processes of NEAT1 in the progression of CRC. Using The Cancer Genome Atlas (TCGA) database and 50 CRC specimens from the First Affiliated Hospital of Dali University, we assessed the expression of NEAT1 to determine its clinical impact. Through gene set enrichment analysis (GSEA), Cancer Single-cell State Atlas (CancerSEA), and immune infiltration studies, we elucidated key functions of NEAT1. We utilized Cell Counting Kit-8 (CCK8), wound healing, and Transwell assays to investigate the role of NEAT1 in the progression of CRC. Through the use of GSEA and immunohistochemistry, additional investigations were conducted to unveil the downstream targets of NEAT1 and gain insights into their regulatory dynamics. Our in vitro studies confirmed the regulatory role of NEAT1 in CRC. Findings indicate that increased NEAT1 expression correlates with adverse outcomes in colorectal tissues. In the CRC model, reduced levels of NEAT1 lead to reduced cell proliferation, invasion, and migration. Additionally, NEAT1 influenced immune cell infiltration in CRC and functioned as an oncogene by upregulating Sirtuin 1 (SIRT1) expression. This study demonstrates that NEAT1 promotes CRC progression and metastasis through a SIRT1-mediated mechanism, suggesting its potential as a prognostic biomarker and therapeutic target for CRC.

RNA, Long Noncoding↗

PubMed1999

[Hereditary colorectal cancer].

About 13% of all colorectal cancer may be dominantly inherited. This amounts to about 300 new cases a year in Norway. Colorectal cancer can be cured by early diagnosis and treatment. Coloscopy with polypectomy may prevent infiltrating cancer. Affected families should be offered genetic evaluation, and family members subjected to regular colonoscopy. The genetic bases of five colorectal cancer syndromes, accounting for most cases of hereditary early onset colorectal cancer, have now been determined. These are familial adenomatous polyposis, colon-endometrial cancer (hereditary non-polyposis colon cancer), Cowden's syndrome, Peutz-Jegher's syndrome and juvenile polyposis. These account for at most 3% of all colorectal cancers. In this group, predictive genetic testing may be employed in families with known mutation. Demonstration of mutation carriers by predictive testing must be based on health service available to the persons at risk. With regard to prophylactic measures, experimental and epidemiological data suggest a preventive effect of aspirin and resistant starch. Empirical information on the effect of intervention is insufficient; multicentre studies are needed.

Adenomatous Polyposis Coli↗

PubMed2000

Interest in genetic testing among first-degree relatives of colorectal cancer patients.

PURPOSE: The present study examined colorectal cancer screening behaviors, risk perceptions, and willingness to receive genetic testing to determine colorectal cancer susceptibility. METHODS: We recruited 95 first-degree relatives of colorectal cancer patients, then conducted a brief telephone interview using a structured questionnaire that elicited information on sociodemographics, cancer screening behaviors, risk perceptions, and interest in genetic testing. RESULTS: Among these high-risk individuals who were aged 40 years or older, only 31% reported fecal occult blood testing within the past year and 59% reported undergoing sigmoidoscopy or colonoscopy within the past 5 years. The majority of participants believed their relative risk of colorectal cancer was increased (68%). Eighty-four percent of the participants indicated that they would have a genetic test if one were available. Participants who believed that <50% of colorectal cancers were caused by heredity were more likely to be interested in genetic testing than were participants who believed that 50% or more of colorectal cancers were caused by heredity. Referral source, sociodemographic factors, clinical factors, and perceived personal risk were not significantly associated with interest in genetic testing. CONCLUSION: Our results suggest that the demand for colorectal cancer susceptibility testing may be high among individuals with a family history of colorectal cancer. We also observed that a substantial number of first-degree relatives were not adhering to colorectal cancer screening guidelines. Accurate information on the genetic aspects of colorectal cancer and the benefits and limitations of genetic testing may help relatives of colorectal cancer patients make informed decisions about whether to undergo enhanced screening and genetic testing.

Adolescent↗

PubMed2006

Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking.

AIM: To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer (HNPCC) patients. METHODS: Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC. RESULTS: Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P < 0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P < 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P < 0.05), hMLH1 smokers (P < 0.1) and hMSH2 smokers (P < 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P < 0.05). Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P < 0.05). CONCLUSION: CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Surgery of colorectal cancer: beyond the frontiers.

Colorectal cancer is a significant health problem in Western countries and is expected to grow further as life expectancy increases. Different surgical techniques have improved the treatment of colorectal cancer. Three controversial treatment modalities are reviewed: laparoscopic surgery for colon cancer, total mesorectal excision, and adjuvant radiotherapy in the management of rectal cancer. Finally, recent advances in the molecular biology of sporadic colorectal cancer are discussed.

Colorectal Neoplasms↗

PubMedDate not supplied

The role of colonoscopy in screening persons with family history of colorectal cancer.

First-degree relatives of colorectal cancer patients are at increased risk for developing colorectal neoplasms. In order to assess the potentiality of colonoscopy screening in this high-risk population, 213 asymptomatic family members (age range 30-69 years, mean 42.8 years) of those patients with colorectal cancer received colonoscopic examination at Chang-Gung Memorial Hospital from April 1992 to May 1994. Twenty-eight persons with 42 lesions (polyps or cancer) were identified, including 28 adenomas, nine hyperplastic polyps and five adenocarcinomas. The positive detection rate was 9.9% for adenoma and 2.3% for cancer. Colorectal neoplasms afflicted males more frequently than females (16.7 vs 5.7%, P < 0.05) and occurred less frequently in those < 40 years of age (5.5 vs 17.2%, P < 0.05). Forty-two per cent of the detected neoplastic lesions were beyond the reach of 60 cm flexible sigmoidoscopy and 36% of adenomas were < 0.5 cm in size and would be missed if patients were screened by air contrast barium enema. Cost analysis revealed that the charges of both screening colonoscopy and screening flexible sigmoidoscopy/air contrast barium enema were approximate. Colonoscopy also has a high acceptability and safety. It appears appropriate to use colonoscopy, rather than flexible sigmoidoscopy or air contrast barium enema, as an initial screening procedure for persons with a family history of colorectal cancer, especially those > 40 years of age.

Adenoma↗

PubMed2003

Quantitative analysis of lymphangiogenic markers in human colorectal cancer.

Lymphatic spread of colorectal cancer cells to regional lymph nodes is one of the early events in metastatic cancer, and is often associated with distant metastatic spread and a poor prognosis. This study examined lymphangiogenic factors, and in particular a panel of newly discovered lymphangiogenic markers, in colorectal cancer tissues from a cohort of patients. Paired samples (background normal mucosa and cancer) of colon tissue were obtained from patients with colorectal cancer. The expression and levels of the VEGF-C and VEGF-D cytokines, the VEGF receptors VEGFR-2 and VEGFR-3, and newly described lymphatic endothelial markers, LYVE-1, Prox-1, podoplanin and 5'-nucleotidase were assessed. RNA was extracted from the frozen colon tissues. The level of expression for each factor/marker was determined using RT-PCR and quantified using a real-time quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as internal standards. VEGF-D was expressed to a significantly higher degree in the colon tumour tissues. There was no significant difference between the expression levels for both VEGF-C and its receptor, VEGFR-2, in background and cancer tissues. However, levels of the VEGFR-3 receptor were found to be significantly higher in colon cancer than the normal background tissues. LYVE-1 levels were below detection in most cases. There was a significant increase in the degree of Prox-1 and 5'-nucleotidase expression in colon cancer tissue. Podoplanin expression was also increased in the cancer samples. These markers indicate an increase in lymphangiogenesis in colon cancer, and may therefore have prognostic value for colon cancer patients.

5'-Nucleotidase↗

PubMed2006

Assessment of risk-independent follow-up to detect asymptomatic recurrence after curative resection of colorectal cancer.

BACKGROUND AND AIMS: Colorectal cancer is one of the leading causes of cancer death. We analyzed the value of standardized, risk-independent postoperative surveillance. MATERIALS AND METHODS: Between 1995 and 2001, 564 patients with colorectal cancer underwent standardized oncologic resection. One hundred thirty-four were unable to take part in the surveillance program, while 430 patients were grouped as follows: group I (n=272, risk-independent follow-up), group II (n=113, follow-up at other departments), and group III (n=45, no follow-up). RESULTS: The 5-year cancer-specific survival rate for UICC III and IV was significantly higher in group I (87%) as compared to group II (35%). In group I, the 5-year disease-free survival rate was 70%. Cancer recurrence occurred at mean 17 (+/-12) months after colorectal resection and yielded a 5-year survival rate of 63%. Reresection was performed in 17 (35%) patients, of whom ten remained disease-free (5-year survival rate, 91%). The money spent for one patient's 5-year follow-up was 1665. CONCLUSIONS: A standardized, risk-independent follow-up program allows early diagnosis of asymptomatic recurrence of colorectal cancer. Reresection improves the 5-year survival rate in this setting.

Aged↗

PubMed2003

First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer.

BACKGROUND & AIMS: The risk of colorectal cancer in relatives of patients with adenomatous colonic polyps is not well defined. This study assessed whether finding colonic neoplasia during screening colonoscopy was related to the family history of colorectal cancer among the participants' parents and siblings. METHODS: Self-reported family history of colorectal cancer was recorded for all participants in a screening colonoscopy study. The size and location of all polyps were recorded before their removal and histologic examination. Participants were grouped according to the most advanced lesion detected. RESULTS: Three thousand one hundred twenty-one patients underwent complete colonoscopic examination. Subjects with adenomas were more likely to have a family history of colorectal cancer than were subjects without polyps (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.09-1.70). The finding of a small (<1 cm) tubular adenoma as the most advanced lesion was associated with only a modest increase in the OR of colorectal cancer in family members (OR, 1.26; 95% CI, 0.99-1.61), but the presence of an advanced adenoma was associated with a higher OR (OR, 1.62;5% CI, 1.16-2.26). Younger age of adenoma diagnosis was not related to a higher prevalence of a family history of colorectal cancer. CONCLUSIONS: Relatives patients with advanced colorectal adenomas have an increased risk of colorectal cancer. Individuals with advanced colorectal adenomas should be counseled about the increased risk of colorectal cancer among their relatives.

Adenoma↗

PubMedDate not supplied

Colorectal cancer risk in first-degree relatives of patients with colorectal adenomatous polyp.

BACKGROUND/AIMS: To evaluate any risk of colorectal cancer in first-degree relatives of patients with colorectal adenomatous polyp. METHODOLOGY: In a screening program-based cross-sectional study, 44821 subjects received an immunochemical fecal occult blood test using a 2-consecutive-day method. They were divided into two groups, according to the results of a self-completed questionnaire on family history of colorectal adenomatous polyps, and the positivity rate of an immunochemical fecal occult blood test as well as the positive predictive value for colorectal cancer were determined in these two groups. RESULTS: The fecal occult blood test was positive in 8.5% of subjects with family history and in 4.8% of subjects without family history, and the positive predictive value for colorectal cancer was 6.8% and 2.4% in subjects with and without family history of colorectal adenomatous polyps, respectively, indicating a significant difference in the positivity rate of the fecal occult blood test (P < 0.01) as well as the positive predictive value for colorectal cancer (P < 0.05) between these two groups. CONCLUSIONS: These results show that first-degree relatives of patients with colorectal adenomatous polyp have an increased risk for colorectal cancer, and that the subjects with family history of colorectal adenomatous polyps as well as cancers should be considered as a priority group for prevention of colorectal cancer.

Adenocarcinoma↗

PubMed2004

Review article: balancing the ideal versus the practical-considerations of colorectal cancer prevention and screening.

Colorectal cancer is responsible for over 500 000 deaths annually world-wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average- or high-risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.

Barium Sulfate↗

PubMed1988

[Clinical study of postoperative infection of gastrointestinal cancer. Randomized study of preventive efficacy of cefmetazole versus cephalothin in postoperative infection of gastric and colorectal cancer].

Effectiveness of prophylactic administration of cefmetazole (CMZ) (A) for postoperative infection was compared with that of cephalothin (B) using patients undergoing resection of gastric cancers or colorectal cancers as subjects in cooperation with 19 major hospitals in the Tohoku districts. Using the envelope method, each hospital allocated, at random, patients with each organ removed into groups A and B. Either drug was administrated at 4 g/day (in 2 divided doses) for 7 days. Registered patients with gastric cancers amounted to 114 in group A and 113 in group B; those with colorectal cancers were 63 each in groups A and B. As to background factors, advanced cancers were found more in group A with gastric cancers, and operations took more time on the average in this group; however, there were no significant differences in other factors between the 2 groups with gastric cancers and in the all factors between A and B groups with colorectal cancers. Rates of ineffective prophylaxis judged by physicians in charge were 3.9% and 21.0%, respectively, in groups A and B with gastric cancers, and 5.0% and 20.7%, respectively, in groups A and B with colorectal cancers. Rates of ineffective prophylaxis determined by committees were 16.7% and 31.0% among the former, and 8.3% and 29.3% among the latter, respectively. Ineffectiveness rates in group A with gastric cancers or colorectal cancers were significantly lower in all the evaluations, and CMZ was, therefore, comfirmed to have stronger efficacy.

Bacterial Infections↗

PubMed2003

Inter-endoscopist variation in polyp and neoplasia pick-up rates in flexible sigmoidoscopy screening for colorectal cancer.

BACKGROUND: The Norwegian Colorectal Cancer Prevention study is an ongoing flexible sigmoidoscopy (FS) screening trial for colorectal cancer. Twenty-one thousand average-risk individuals, aged 50-64 years, living in two separate areas in Norway were randomly drawn from the Population Registry and invited to once-only screening flexible sigmoidoscopy. Examinations were performed over 3 years, at 2 centres, by 8 different endoscopists, using the same type of equipment. The aim of the present study was to investigate possible differences between endoscopists in detecting individuals with polyps, adenomas and advanced lesions (adenomas with severe dysplasia and/or villous components and/or size larger than 9 mm and carcinoma) in flexible sigmoidoscopy screening. METHODS: The present trial comprises data from 8822 individuals, aged 55-64 years, who have undergone a flexible sigmoidoscopy. In the study period, all lesions detected by the different endoscopists were registered. Tissue samples were taken from all lesions detected. RESULTS: Detection rates varied significantly between endoscopists, ranging from 36.4% to 65.5% for individuals with any polyp, from 12.7% to 21.2% for any adenoma and from 2.9% to 5.0% for advanced lesions. In a multiple logistic regression model, the performing endoscopist was a strong independent predictor for detection of individuals with polyps (P < 0.001 ), adenomas (P < 0.001) and advanced lesions (P = 0.01). CONCLUSION: Detection rates for colorectal lesions vary significantly between endoscopists in colorectal cancer screening. Establishing systems for monitoring performance in screening programmes is important. Supervised training and re-certification for endoscopists with poor performance should be considered.

Clinical Competence↗

PubMedDate not supplied

Colorectal cancer in young patients.

Colorectal cancer is rare in patients under 40 years of age. We reviewed all colorectal cancer patients treated at the First Department of Surgery of the University of Rome, to determine the true incidence of large bowel cancer in young patients. During the period 1978-1984 a total of 571 patients were indexed. Out of these 44 were 39 years of age or less. A group of 527 patients 40 years of age or over served as a control. Neoplasms were localized in the right colon in 19 cases and in the left colon in 25 patients, in the young group. In the control group 178 patients presented neoplasms localized in the right colon, while 349 presented tumors localized in the left colon. According to tumor advancement in the young group tumor classification from A stage tumor through D stage was: 4, 6, 14, 5, 9, 6. In the control group 22 patients presented A stage tumors, 106 B1, 139 B2, 50 C1, 118 C2, 92 D tumors. The operability rate was 93.2% in the young group, and 92% in the old one. The operative mortality rate was 0% in the young group, and 2.5% in the old one. Four complications occurred in the young patients, and 57 in the old patients. The five years survival rate was 56.7% and 52.1% in young and old patients respectively. The results of our study indicate that there are no significant differences in prognosis and five years survival in young patients with colorectal cancer.

Adenocarcinoma↗

PubMed2004

[Patterns of metachronous adenoma after colorectal cancer surgery].

BACKGROUND/AIMS: After colorectal cancer surgery, colonoscopic surveillance should be done for prevention and early detection of secondary cancer. This study aimed to identify the group with high risk of developing colorectal adenoma after curative surgery of colorectal cancer. METHODS: We retrospectively investigated the medical records of the subjects of 130 patients who had been examined using colonoscopy before and after the curative surgery. RESULTS: The average age was 59.4 years. Synchronous adenomas were in 42 patients (32.3%). The occurrence rate was significantly high in men (38.8%) than women (22.0%). After the operation, the mean interval of examining colonoscopy was 11.6 months (3-24 months) and metachronous adenomas were detected in 26 patients (20.0%). The patients who have both metachronous and synchronous adenomas were observed in 13/42 (30.9%) and the patients of metachronous adenomas without synchronous adenomas were observed in 13/88 (14.8%). The occurrence rate of metachronous adenomas with synchronous adenomas was significantly high. The frequency of synchronous adenomas didn't increase with age. However, the frequency of metachronous adenomas increased with age: 0/9 (0%) under 40 years, 7/49 (14.3%) in 41-61 years and 19/72 (26.4%) over 61 years. The occurrence rate was higher in men (26.3%) than women (10.0%). CONCLUSIONS: The occurrence rate of metachronous adenomas after colorectal cancer surgery was higher in the patients with synchronous adenomas, male gender and old aged patients.

Adenoma↗