National Cancer Institute®
Last Modified: January 1, 2002
UI - 11483640
AU - Michie S; Bobrow M; Marteau TM
TI - Predictive genetic testing in children and adults: a study of emotional impact.
SO - J Med Genet 2001 Aug;38(8):519-26
AD - Psychology and Genetics Research Group, Guy's, King's, and St Thomas's Medical School, King's College London, Guy's Campus, London SE1 9RT, UK. firstname.lastname@example.org
AIM: To determine whether, following predictive genetic testing for familial adenomatous polyposis (FAP), children or adults receiving positive results experience clinically significant levels of anxiety or depression, and whether children receiving positive results experience higher levels of anxiety or depression than adults receiving positive results. DESIGN: Two studies, one cross sectional and one prospective. SAMPLE: 208 unaffected subjects (148 adults and 60 children) at risk for FAP who have undergone genetic testing since 1990. MAIN MEASURES: Dependent variables: anxiety, depression; independent variables: test results, demographic measures, psychological resources (optimism, self-esteem). RESULTS: Study 1. In children receiving positive results, mean scores for anxiety and depression were within the normal range. There was a trend for children receiving positive results to be more anxious and depressed than those receiving negative results. In adults, mean scores for anxiety were within the normal range for those receiving negative results, but were in the clinical range for those receiving positive results, with 43% (95% CI 23-65) of the latter having scores in this range. Regardless of test result, adults were more likely to be clinically anxious if they were low in optimism or self-esteem. Children receiving positive or negative results did not experience greater anxiety or depression than adults. Study 2. For children receiving a positive test result, mean scores for anxiety, depression, and self-esteem were unchanged over the year following the result, while mean anxiety scores decreased and self-esteem increased after receipt of a negative test result over the same period of time. CONCLUSION: Children, as a group, did not show clinically significant distress over the first year following predictive genetic testing. Adults were more likely to be clinically anxious if they received a positive result or were low in optimism or self-esteem, with interacting effects. The association between anxiety, self-esteem, and optimism suggests that counselling should be targeted, not only at those with positive test results, but also at those low in psychological resources.
UI - 11606402
AU - Heinimann K; Thompson A; Locher A; Furlanetto T; Bader E; Wolf A; Meier
TI - R; Walter K; Bauerfeind P; Marra G; Muller H; Foernzler D; Dobbie Z Nontruncating APC germ-line mutations and mismatch repair deficiency play a minor role in APC mutation-negative polyposis.
SO - Cancer Res 2001 Oct 15;61(20):7616-22
AD - Research Group Human Genetics, Division of Medical Genetics, University Clinics, 4031 Basel, Switzerland. email@example.com
Familial adenomatous polyposis, an autosomal-dominantly inherited colorectal cancer predisposition syndrome, is caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. Despite the use of different screening methods, studies worldwide fail to identify APC mutations in 20-50% of all familial adenomatous polyposis patients (APC mutation-negatives). In this study, missense mutations in the coding region of the APC gene, which would have been missed by the protein truncation test, as well as mutations in the APC promoter and the 3' untranslated region, were determined by the single nucleotide polymorphism discovery assay and direct DNA sequencing in 31 mutation-negative polyposis patients. Seventeen gene alterations were identified, whereof four (12.9%) represent possibly pathogenic germ-line mutations: silent A290T (promoter) and A8822G (3' untranslated region) as well as missense R99W and E1317Q (coding region). The 27 remaining, truly APC mutation-negative polyposis patients displayed a significantly later age at diagnosis compared with APC mutation carriers (46.1 versus 35.2 years; P < 0.01). APC mutation-negative individuals with >100 colonic polyps were more likely to present with extracolonic disease (P < 0.05) than those with <100. Assessment of microsatellite instability (MSI), a hallmark of mismatch repair deficiency, in 68 tumors from 21 truly APC mutation-negative patients, identified 4 (5.9%) unstable tubulo-villous adenomas (3 MSI-High and 1 MSI-Low), stemming from 4 (19%) unrelated individuals and likely to be caused by hMLH1 promoter hypermethylation. In conclusion, only a small proportion of APC germ-line mutation carriers is missed by the protein truncation test, and mismatch repair deficiency does not seem to substantially contribute to tumor development in APC mutation-negative polyposis patients.
UI - 11600806
AU - Pistorius S; Schackert HK; Saeger HD
TI - [Hereditary colorectal carcinomas - reflection on preventive surgery]
SO - Onkologie 2001 Sep;24 Suppl 5():4-8
AD - Klinik und Poliklinik fur Viszeral, Thorax und Gefasschirurgie, Universitatsklinikum Carl Gustav Carus, TU Dresden, Germany. firstname.lastname@example.org
Nonpolyposis Colorectal Cancer (HNPCC) accounts for about 5% of all colorectal cancers and is the most frequent familial form; familial adenomatous polyposis coli accounts for about 1%. Prerequisitive for individually tailored surveillance is the identification of the pathogenic germline mutation. In classical FAP, surgical standard is a restorative proctocolectomy while in HNPCC there is no surgical standard other than standard oncological resection due to missing evidence. In HNPCC, prophylactic colectomy before the onset of the first colorectal cancer is not recommended. Main arguments for the extension of the resection in the case of the first colorectal carcinoma in HNPCC are the rate of metachronous colorectal carcinomas of 40-45% in a 10-year interval and rapid tumor progression. In HNPCC, in the case of first colon cancer a subtotal colectomy seems to be indicated. A proctocolectomy or, if indicated, a restorative proctocolectomy may be considered in the case of carcinomas in the lower rectum. These considerations should be evaluated in a prospective clinical trial. Counselling, molecular diagnosis and surgery in patients with hereditary colorectal cancers should only be performed in interdisciplinary centers. Copyright 2001 S. Karger GmbH, Freiburg
UI - 11680173
AU - Abramowicz M
TI - [Genetic aspects of colorectal cancer]
SO - Rev Med Brux 2001 Sep;22(4):A199-202
AD - Service de Genetique Medicale, Centre de Genetique, Laboratoire de Genetique Medicale, Hopital Erasme, U.L.B.
Cancer is a hereditary disease at the level of an individual cell and its daughter cells. The tumor genotype causing the tumor phenotype is now quite well known in colorectal cancer and allows, among others, to perform pathology examination at the molecular level. A distinct topic addresses individual predisposition to colorectal cancer. Its molecular nature is well know in the relatively rare cases, about 5-10% of colorectal cancers, where such a predisposition is major, and is transmitted in families of affected subjects following a hereditary, mendelian mode of inheritance. Specifically, two types of hereditary adenomatous tumors, polyposis and hereditary nonpolyposis colorectal cancer, may benefit from genetic analysis in order to target cancer prevention. New genetic tests will probably develop in the coming years, allowing for the analysis of more modest, and less clearly hereditary individual risks.
UI - 11680042
AU - Tejpar S; Cassiman JJ; Van Cutsem E
TI - The molecular basis of colorectal cancer.
SO - Acta Gastroenterol Belg 2001 Jul-Sep;64(3):249-54
AD - Center for Human Genetics, University of Leuven, Herestraat 49, 3000 Leuven, Belgium. Sabine.email@example.com
Colorectal cancers, whether sporadic or hereditary, are caused by a defined set of molecular events. The genes and pathways involved in the earliest steps of tumorigenesis have crucial functions in the regulation of normal crypt homeostasis. Further insight into these pathways can lead to the development of useful prognostic indicators, and target preventive and therapeutic strategies in the management of colorectal cancer. Mutations in the APC/beta-catenin/Tcf-4 pathway lead to important changes in stem cell dynamics, before clinically identifiable lesions appear. Preventive strategies aimed at reversing these changes or therapeutic interventions targeting cell populations with these alterations should be most efficacious.
UI - 11693343
AU - Raedle J; Friedl W; Engels H; Koenig R; Trojan J; Zeuzem S
TI - A de novo deletion of chromosome 5q causing familial adenomatous polyposis, dysmorphic features, and mild mental retardation.
SO - Am J Gastroenterol 2001 Oct;96(10):3016-20
AD - 2nd Department of Internal Medicine and Institute of Human Genetics, University of Frankfurt/Main, Frankfurt am Main, Germany.
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that typically presents with colorectal cancer secondary to extensive adenomatous polyps of the colon. The molecular basis and clinical phenotype of FAP are well known. Recurrent episodes of severe abdominal pain and a positive fecal occult blood test in an 18-yr-old boy with mild mental retardation and slight dysmorphic features of the face, head, and skeletal system led to the diagnosis of FAP. The clinical workup revealed the presence of over 100 sessile colonic polyps but no polyp formation in the upper GI tract, no cancer development, nor other FAP-associated lesions. To find out whether there is an association between mental retardation and FAP we performed a chromosome analysis including comparative genomic hybridization and an indirect genotype analysis with polymorphic markers from the APC gene region. Cytogenetic analysis showed an interstitial deletion of chromosomal region 5q that was confined to the region 5q21-q22 by comparative genomic hybridization. The deletion, spanning about 10 centimorgans, encompassed the complete APC gene and can be considered as causative for FAP. Moreover, molecular genetic analysis with polymorphic markers flanking the APC gene demonstrated a de novo deletion on the paternal chromosome. Cytogenetically detectable deletions on chromosome 5 including the APC gene generally lead to an associated gene deletion syndrome. Individuals who present with mild mental retardation and dysmorphic features should therefore be investigated for chromosomal deletions. If the deletion encompasses the APC gene, these patients are at high risk of developing FAP and associated complications.
UI - 11713930
AU - Lynch HT; Thorson AG; McComb RD; Franklin BA; Tinley ST; Lynch JF
TI - Familial adenomatous polyposis and extracolonic cancer.
SO - Dig Dis Sci 2001 Nov;46(11):2325-32
AD - Department of Preventive Medicine, Creighton University School of Medicine Omaha, Nebraska 68178, USA.
Our purpose is to focus attention on the cancer family history, coupled with an understanding of the natural history and extracolonic tumor spectrum of familial adenomatous polyposis (FAP), through a family study. This family report provides an example of how colorectal cancer (CRC) can be prevented by knowledgeable gastroenterologists and colorectal surgeons who educate and compassionately counsel members of high-risk families so that their compliance with diagnostic screening and, ultimately, with protection through prophylactic colectomy, is achieved. A working pedigree of this extended family was constructed through interviews with the proband, followed by questionnaires sent to all primary and secondary relatives. Appropriately signed permission forms enabled us to secure pertinent medical and pathology records in order to ensure accuracy of historical information. Integral extracolonic tumors included medulloblastoma, papillary thyroid carcinoma, hepatoblastoma, and desmoid tumors. We conclude that, due in part to improved longevity as a result of being spared CRC, several family members have developed certain FAP integral extracolonic cancers.
UI - 11711728
AU - Wallace MH; Forbes A; Beveridge IG; Spigelman AD; Hewer A; Venitt S;
TI - Phillips RK Randomized, placebo-controlled trial of gastric acid-lowering therapy on duodenal polyposis and relative adduct labeling in familial adenomatous polyposis.
SO - Dis Colon Rectum 2001 Nov;44(11):1585-9
AD - ICRF Colorectal Cancer Unit and The Polyposis Registry and the Academic Institute, St. Mark's Hospital, Northwick Park, Harrow, United Kingdom.
PURPOSE: Bile has been implicated in the pathogenesis of duodenal polyps in patients with familial adenomatous polyposis. In vitro experiments have shown that familial adenomatous polyposis bile is capable of producing DNA adducts. This effect can be ameliorated by increasing the pH of the incubate. The aim of this double-blind randomized placebo-controlled trial was to examine the effect of oral ranitidine on duodenal polyposis in a group of patients with familial adenomatous polyposis. METHODS: Twenty-six patients with familial adenomatous polyposis were randomly assigned to ranitidine 300 mg daily or placebo for six months after baseline endoscopy. Polyp counts were performed and biopsy specimens taken to detect DNA adducts by 32P-postlabeling. RESULTS: No difference was seen in polyp numbers (P = 0.9) or relative adduct labeling (P = 0.7) after treatment with ranitidine or placebo. DISCUSSION: Acid suppression therapy does not seem to improve duodenal polyposis despite in vitro findings. On the other hand, ranitidine does not exacerbate actual (or markers of) neoplasia in this highly tumor-prone condition.
UI - 11711730
AU - Ponz de Leon M; Varesco L; Benatti P; Sassatelli R; Izzo P; Scarano MI;
TI - Rossi GB; Di Gregorio C; Gismondi V; Percesepe A; de Rosa M; Roncucci L Phenotype-genotype correlations in an extended family with adenomatosis coli and an unusual APC gene mutation.
SO - Dis Colon Rectum 2001 Nov;44(11):1597-604
AD - Dipartimento di Medicina Interna, Universita di Modena, Modena, Italy.
PURPOSE: Genotype-phenotype correlations in familial adenomatous polyposis are only partially understood and, in particular, little is known about the biomolecular characteristics of desmoid tumors, which are one of the most serious and frequent manifestations of familial adenomatous polyposis. In the present study, we describe a family with familial adenomatous polyposis, with peculiar clinical characteristics (i.e., frequency and severity of desmoid neoplasms) associated with an unusual mutation of the adenomatosis polyposis coli gene. If confirmed by other investigations, these findings might help to understand the biologic mechanisms by which specific adenomatosis polyposis coli mutations predispose to desmoid tumors. METHODS: The family with familial adenomatous polyposis, living in southern Italy, was studied from 1985 to the end of 1999; at this date, 15 individuals have been affected by histologically verified familial adenomatous polyposis, 11 of whom had desmoid tumors. A total of 19 family members were studied for adenomatosis polyposis coli gene mutations; 13 of them tested positive and 6 negative. The analytical procedure-previously described-consisted of the extraction of peripheral blood cell DNA, amplification of exon 15 by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing of the DNA fragment containing the mutation. RESULTS: The main clinical features of the family were 1) a high frequency of desmoid tumors and, consequently, a high penetrance of the desmoid trait in all branches of the family and in 11 (73.3 percent) of 15 affected individuals and 2) severity of desmoids in at least 4 family members, 2 of whom died for causes related to the presence of these tumors. The molecular basis of the disease was an uncommon mutation of the adenomatosis polyposis coli gene, consisting of a large deletion of 310 base pairs at codon 1,464, with duplication of the breakpoint (4,394ins15del310), leading to a stop codon at position 1,575. CONCLUSIONS: The present study shows that a truncating mutation in the adenomatosis polyposis coli gene at the beginning of the region frequently associated with desmoids induced a familial adenomatous polyposis phenotype featured by a high penetrance of the desmoid trait, with severe disease in several affected members of both sexes. The study may help to understand the biologic mechanisms of genotype-phenotype correlations in adenomatosis coli.
UI - 9321987
AU - Hughes-Fulford M; Boman B
TI - Growth regulation of Gardner's syndrome colorectal cancer cells by NSAIDs.
SO - Adv Exp Med Biol 1997;407():433-41
AD - Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA, USA.
UI - 11685545
AU - Takafuji V; Lublin D; Lynch K; Roche JK
TI - Mucosal prostanoid receptors and synthesis in familial adenomatous polyposis.
SO - Histochem Cell Biol 2001 Aug;116(2):171-81
AD - Department of Internal Medicine, Box 801317, MR-4 Building, University of Virginia Health System, Charlottesville, VA 22908, USA.
Chronic ingestion of non-steroidal anti-inflammatory medication is reported to delay or, in part, reverse development of polyps in the colon, but the mechanism for this effect is unknown. Using mRNA and immunoglobulin probes, specific for prostanoid receptors and for prostaglandin endoperoxide synthase (COX 1 and 2), we sought to define, by in situ and in vitro techniques, changes in PGE2 receptors and synthesis in cell populations of precancerous familial adenomatous polyposis (FAP) colonic mucosa. In FAP, expression of prostanoid receptors EP3 and EP4 among colonic lamina propria mononuclear and lateral crypt epithelial cells was robust, with 53.9+/-5.3% of mononuclear cells staining EP4+. When sections of normal colonic mucosa were examined by similar techniques, prostanoid receptor EP4 was expressed on only 21.3+/-1.2% of lamina propria mononuclear cells (including CD4+ T lymphocytes), as well as on surface and lateral crypt epithelium, and this distribution was found at the mRNA level as well. When receptor expression was quantitated by densitometry, immunoreactive EP3 protein on deep basolateral (but not other) FAP crypt epithelium was enhanced 2.8-fold over normal, and the number of prostanoid receptor EP4+ mononuclear cells by 2.5-fold. On the other hand, while COX 1 expression in mononuclear cells was prominent in normal and FAP mucosa, densitometric analysis showed immunoreactive prostaglandin endoperoxide synthase levels were further increased in FAP, due to a greater than fourfold elevation of COX 2 expression among mononuclear cells and epithelia. Our data suggest enhanced cell-specific prostanoid receptor expression and increased prostanoid synthesis in precancerous FAP mucosa.
UI - 10980114
AU - Abraham SC; Nobukawa B; Giardiello FM; Hamilton SR; Wu TT
TI - Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations.
SO - Am J Pathol 2000 Sep;157(3):747-54
AD - Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Fundic gland polyps (FGPs) are the most common gastric polyps in patients with familial adenomatous polyposis (FAP). FGPs have traditionally been regarded as nonneoplastic, possibly hamartomatous lesions, but the pathogenesis of FGPs in both FAP and sporadic patients remains unclear. FGPs in FAP can show foveolar dysplasia, and rarely invasive gastric adenocarcinoma has been reported in patients with FAP and fundic gland polyposis. Using direct gene sequencing and allelic loss assays at 5q, we analyzed somatic adenomatous polyposis coli (APC) gene alterations in 41 FAP-associated FGPs (20 with foveolar dysplasia, six indefinite for dysplasia, and 15 nondysplastic) and 13 sporadic FGPs. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 25 of 41 FAP-associated FGPs and 13 of 13 sporadic FGPs. Somatic APC gene alterations were identified frequently (21 of 41 cases, 51%) in FAP-associated FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the FGPs were shown to carry the same somatic APC gene alteration in 24 (96%) of 25 cases. Furthermore, there was no difference in the frequency of somatic APC gene alterations between FGPs with foveolar dysplasia (10 of 20, 50%), indefinite for dysplasia (four of six, 67%), and nondysplastic (seven of 15, 47%) in FAP patients (P: = 0.697). In contrast, FGPs from non-FAP patients showed infrequent (one of 13, 8%) APC gene alterations (P: = 0.008). These results show that FGPs in FAP patients are pathogenetically distinct from sporadic FGPs. Somatic, second-hit APC gene alterations, which precede morphological dysplasia in many FAP-associated FGPs, indicate that FGPs arising in the setting of FAP are neoplastic lesions.
UI - 11731419
AU - Boman BM; Fields JZ; Bonham-Carter O; Runquist OA
TI - Computer modeling implicates stem cell overproduction in colon cancer initiation.
SO - Cancer Res 2001 Dec 1;61(23):8408-11
AD - Division of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Bruce.Boman@mail.tju.edu
On the basis of our investigation of the premalignant crypt phenotype in familial adenomatous polyposis patients, the hypothesis is developed that tumor initiation in the colon is caused by crypt stem cell overproduction. A novel kinetic model for the colonic crypt was used to investigate how the earliest tissue abnormality (altered crypt labeling index) arises in these patients who have a mutant APC genotype. Only an increase in crypt stem cell number, not changes in the rate of cell cycle proliferation, differentiation, or apoptosis of the non-stem cell population, simulated this abnormality. This suggests that APC regulates the number of stem cells in the colonic crypt and when the cells become mutant, an expansion of the crypt stem cell population results.
UI - 11605029
AU - Strippoli P; Sarchielli S; Santucci R; Bagnara GP; Brandi G; Biasco G
TI - Cold single-strand conformation polymorphism analysis: optimization for detection of APC gene mutations in patients with familial adenomatous polyposis.
SO - Int J Mol Med 2001 Nov;8(5):567-72
AD - Institute of Histology and Embryology, University of Bologna, I-40138 Bologna, Italy.
Over 200 adenomatous polyposis coli (APC) gene mutations have been described in familial adenomatous polyposis (FAP) patients. Recent single-strand conformation polymorphism (SSCP) screening methods have introduced minigel runs, simple ethidium bromide staining and external temperature control without any loss of sensitivity (cold-SSCP). In order to test the effectiveness in APC mutation detection, cold-SSCP was employed following polymerase chain reaction (PCR) amplification in three patients with FAP. Different running parameter combinations were compared. The three mutations already known were all diagnosed by cold-SSCP. The gel concentration was found to be essential in detecting the single-base substitution in fragments of different lengths. The observation of deletions was not affected by gel concentrations and heteroduplex bands were always produced. The temperature or glycerol addition did not significantly affect sensitivity. This modified cold-SSCP method provides a simple and effective way for detecting several known Apc gene mutations without any loss of sensitivity and could be useful for large-scale molecular diagnosis of FAP.
UI - 11741105
AU - Pang CP; Fan DS; Keung JW; Baum L; Tang NL; Lau JW; Lam DS
TI - Congenital hypertrophy of the retinal pigment epithelium and APC mutations in Chinese with familial adenomatous polyposis.
SO - Ophthalmologica 2001 Nov-Dec;215(6):408-11
AD - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, China. firstname.lastname@example.org
Mutations in the adenomatous polyposis coli gene (APC) often cause both congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). To investigate the relationship between APC mutations, CHRPE and FAP, all FAP patients at the Prince of Wales Hospital, Hong Kong, were asked to participate in a study. Ten Chinese patients from 6 kindreds and their family members volunteered, along with 12 healthy control subjects selected among hospital visitors and staff. All were examined for dilated fundus by indirect ophthalmoscopy. Mutations in APC coding exons were detected by sequencing. In one FAP patient, a novel A insertion at codon 1023 was detected. Three previously reported mutations were detected in 6 FAP patients: a deletion of ACAAA at codon 1061, and 2 truncating point substitutions at codons 216 and 283. In 3 FAP patients, no APC mutation was found, suggesting that mutations in APC coding regions are not the sole cause of FAP or CHRPE. A total of 64 CHRPE lesions were found in FAP patients and some relatives with and without APC mutations. Contrary to most reports, APC mutations before exon 9 did cause CHRPE lesions, albeit relatively few. Copyright 2001 S. Karger AG, Basel
UI - 1646139
AU - Olschwang S; Weiffenbach B; Laurent-Puig P; Melot T; Vassal A; Falls K;
TI - Salmon RJ; Parc R; Strong L; Nakamura Y; et al Genetic characterization of the APC locus involved in familial adenomatous polyposis.
SO - Gastroenterology 1991 Jul;101(1):154-60
AD - Laboratory of Tumor Genetics, Institut Curie, Paris, France.
Familial adenomatous polyposis is a rare disease inherited in a Mendelian dominant fashion. It is characterized by the occurrence of more than 100 adenomatous polyps in the large bowels of affected individuals. The genetic defect responsible for adenomatous polyposis resides at a locus called APC which has been localized to the long arm of human chromosome 5. In this study, the APC locus was mapped with respect to 11 markers known to map to this chromosomal segment. Linkage of APC to four of these markers had been previously reported. Three additional markers are shown here to be linked to APC. By multipoint analysis, the APC locus maps to an interval bounded by D5S49 and D5S58. The refined map of the APC locus and the new markers described here improve the informativeness and accuracy of the presymptomatic diagnosis of familial adenomatous polyposis.
UI - 1650309
AU - Moslein G; Kadmon M
TI - [Family screening in familial adenomatous polyposis--organization of a preventive and after care program for patients and risk probands]
SO - Chirurg 1991 Apr;62(4):357-9
UI - 1315892
AU - Huismans H
TI - [Familial adenomatous polyposis from the ophthalmologic viewpoint]
SO - Klin Monatsbl Augenheilkd 1992 Mar;200(3):213-8
Familial adenomatous polyposis is dominant autosomal heritable and pre-cancerous. Characteristic changes of ocular fundus, multiple and bilateral retinal dysplasias, permit diagnosis in presymptomatic stage, significant especially not at least for sporadic cases of polyposis recti and coli, which are 40 per-cent of all. Contrary to often wellknown risk-families this group can't be realized epidemiologically, but complications are the same.
UI - 1316298
AU - Olschwang S; Laurent-Puig P; Melot T; Thuille B; Vassal A; Parc R;
TI - Salmon R; Thomas G [Familial adenomatous polyposis: early diagnosis by genetic mapping]
SO - Gastroenterol Clin Biol 1992;16(3):205-9
AD - Laboratoire de Genetique des Tumeurs, Institut Curie, Paris.
The use of probes detecting polymorphic loci within the human population has enabled accurate localization of the genetic defect responsible for familial adenomatous polyposis on chromosome 5. This was used to screen two families for the presymptomatic diagnosis in children of an affected parent. In both cases, the use of 8 polymorphic probes located on either side of the gene provided information which could be used in the management of children born from the patients at risk. The set of probes used in this work should be informative in most of the affected adenomatous polyposis families.
UI - 1330993
AU - Calmes JM; Rutz HP; Suardet L; Givel JC
TI - [Hereditary colorectal cancer: observations of a family study]
SO - Helv Chir Acta 1992 Aug;59(2):349-54
AD - Service de chirurgie generale, CHUV, Lausanne.
Described in Switzerland in the early '60, the major features of hereditary non-polyposis colon cancer syndrome (HNPCCS) were established 20 years ago by H. T. Lynch. HNPCCS accounts for at least 60% of the colon cancer etiology. Cancer family syndrome is defined by the presence of extracolonic primary tumors in addition to colon cancer. Both syndromes are transmitted by an autosomic dominant pattern. None of the known biomarkers are specific and/or sensitive enough to rely on their predictive values of patient's risks. A typical Swiss family was investigated on the basis of the cancer-prone family history. 21% of the family members observed over 5 generations presented one or more (30% of the cases) colo-rectal neoplasms at the age of 50. 55% of the tumors were right sided. Histologically, half of the tumors were mucinous. 30% of metachronous cancer appeared within 10 years. Polyps (1-3) and flat adenomas were associated to the lesion in 57%. Extra-colonic tumors appeared in 18% of family members and in half of the colon cancer patients. The sites of these tumors were the urinary tract, ovary, small bowel, breast and stomach. Two fibroblast strains of affected individuals were established. No increased tetraploidy was noted. Preliminary results suggest that this two strains are rather sensitive to ionising radiation. Often neglected, family history of colon cancer remains the major diagnostic and decision-making tool of a such syndrome. It will necessitate special treatment of affected subjects and early screening of the relatives.(ABSTRACT TRUNCATED AT 250 WORDS)
UI - 1333171
AU - Koorey DJ; Smith A
TI - Normal high-resolution karyotypes in 26 unrelated individuals with hereditary colorectal neoplasia.
SO - Am J Gastroenterol 1992 Dec;87(12):1736-9
AD - A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
High-resolution karyotype analysis was performed on peripheral blood cultures from 26 patients with hereditary colorectal neoplasia. The aims of this study were: first, to determine the frequency of cytogenetically visible chromosome 5q deletions in familial adenomatous polyposis and, thus, whether routine karyotype analysis should be included in screening regimens for affected families; and, second, to search for chromosomal abnormalities in hereditary nonpolyposis colorectal cancer that might assist in localizing the gene or genes responsible. No cytogenetic abnormalities were detected among 21 unrelated patients with familial adenomatous polyposis and five with hereditary nonpolyposis colorectal cancer. We conclude that cytogenetic analysis is of no value in the management of families with typical familial adenomatous polyposis or Gardner's syndrome, and should be confined to those families with atypical features such as mental retardation or facial dysmorphism.
UI - 8402712
AU - Varesco L; Gismondi V; James R; De Benedetti L; Heouaine A; Biticchi R;
TI - Masetti E; Bertario L; Sala P; Grammatico P; et al APC gene mutations in Italian familial polyposis coli patients.
SO - Cancer Detect Prev 1993;17(2):279-81
AD - Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Adenomatous polyposis coli is an autosomal dominant disease characterized by the development of hundreds of colorectal adenomas in young adults. If prophylactic colectomy is not performed, colorectal cancer develops in virtually all affected individuals by the fifth decade of life. All at-risk relatives older than 10 years of age need to be screened regularly by endoscopy. Recently, the gene responsible for the disease, the APC gene, was cloned. The finding of inactivating mutations of the APC gene in Italian APC patients allowed us to offer DNA-based diagnostic tests to these families.
UI - 2887069
AU - Lisnianskii IE; Gar'kavtseva RF; Zaletaev DV; Kuz'minov AM
TI - [Hereditary multiple endocrine neoplasm syndromes]
SO - Vopr Onkol 1987;33(6):57-61
Three syndromes of multiple endocrine neoplasia (MEN) have been identified to date: MEN--I, IIa and IIb. They involve various combinations of endocrine neoplasia and occur mostly in young patients. Predisposition transmission mechanism is autosomal-dominant with total penetration and variable expressiveness. Patients' families should undergo screening which involves identification of biochemical markers and cytogenetic examination. This would allow identification of subjects at high risk for cancer and improvement of early diagnosis.
UI - 2539335
AU - Paraskeva C; Harvey A; Finerty S; Powell S
TI - Possible involvement of chromosome 1 in in vitro immortalization: evidence from progression of a human adenoma-derived cell line in vitro.
SO - Int J Cancer 1989 Apr 15;43(4):743-6
AD - Department of Pathology, University of Bristol Medical School, UK.
We have previously reported that continuous in vitro passage in the presence of 3T3 feeders of a non-tumorigenic adenoma-derived epithelial cell line, designated PC/AA, resulted in its becoming immortal. At early passage PC/AA was normal diploid, whereas every cell of PC/AA late passage had an isochromosome 1(q) which led us to suggest that abnormalities of chromosome 1 may be involved in tumour progression. We now report the isolation of a 3T3-feeder-independent variant of early-passage PC/AA, designated PC/AA/FI, which was immortal in vitro and remained non-tumorigenic. Each cell of PC/AA/FI again has an isochromosome 1(q), like the late-passage PC/AA. However, with PC/AA/FI it is the other chromosome 1 of the homologous pair which is involved in the formation of the isochromosome 1(q). This is possible to determine because of the polymorphic centromeric heterochromatin on chromosome 1 of the early-passage PC/AA. With the late-passage PC/AA (grown with 3T3 feeders) the homologue with the large C-band has given rise to an isochromosome 1(q) whereas with PC/AA/FI it is the other homologue with the smaller C-band which has given rise to this isochromosome. Both the immortal PC/AA/FI and the immortal PC/AA late passage, therefore, have independent abnormalities involving chromosome 1. These results indicate that chromosome 1 may be involved in in vitro immortalization.
UI - 2843422
AU - Bazhenova MD; Al'tshuler BA
TI - [Assessment of the risk of recurrence isolated cases of dominantly inherited diseases with incomplete penetrance and age-related dependence]
SO - Genetika 1988 May;24(5):947-50
A modification of the method for risk estimation in isolated cases of autosomal dominant disorders with reduced penetrance is presented. It is based on the Bayesian theorem and considers such parameters as fitness, age-specific expressivity of the gene and the effect of parental age on mutation rate. The definite expression of the risk estimation is proposed. Using hereditary polyposis as an example, possible risks are proposed. The table of risks, depending on the parental age, is given.
UI - 8071957
AU - Barber JC; Ellis KH; Bowles LV; Delhanty JD; Ede RF; Male BM; Eccles DM
TI - Adenomatous polyposis coli and a cytogenetic deletion of chromosome 5 resulting from a maternal intrachromosomal insertion.
SO - J Med Genet 1994 Apr;31(4):312-6
AD - Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, UK.
We present the clinical and laboratory findings in an institutionalised adult patient originally referred for autism. A high risk of colorectal cancer was predicted when an interstitial deletion of the long arm of chromosome 5, del(5)(q15q22.3), was detected in her lymphocytes and deletion of the MCC and APC genes confirmed by molecular analysis. Adenomatous polyposis coli and carcinoma of the rectum were subsequently diagnosed in the patient. She was profoundly mentally retarded, autistic, and had minor dysmorphic features consistent with those of previous patients with similar deletions. The deletion arose as a result of recombination within the small insertion loop formed at meiosis by the direct insertion (dir ins(5)(q22.3q14.2q15)) found in the patient's mother. This family further confirms the cytogenetic mapping of both MCC and APC genes to 5q22 and comparison with other recent cases suggests that both genes and their closely linked markers lie within the 5q22.1 subband.
UI - 7706067
AU - Hartig C; Stieler W; Stadler R
TI - [Muir-Torre syndrome. Diagnostic criteria and review of the literature]
SO - Hautarzt 1995 Feb;46(2):107-13
AD - Hautklinik, Minden.
We report on a 63-year-old female patient with Muir-Torre syndrome (MTS). In the course of this disease two carcinomas of the colon, a kerato-acanthoma and multiple sebaceous gland tumours, including four sebaceous carcinomas, appeared. This case is thought to be a hereditary form as one of daughters was also found to have a sebaceous epithelioma. MTS is a mostly autosomal-dominant disease with the association of sebaceous gland tumours and internal carcinomas. As the malignant tumours only show slight aggressiveness the prognosis is quite favourable. Oral isotretinoin therapy was successfully used for the inhibition of sebaceous gland proliferation. A narrower definition is presented and an updated survey of the published cases is given. Furthermore, the histopathologic peculiarities of sebaceous gland tumours, especially of sebaceous gland carcinomas, are discussed and compared to sebaceous gland tumours not connected with MTS. A total number of 100 of the 135 published cases of MTS were included and analysed regarding sebaceous gland tumours and other skin tumours. The data on internal carcinomas were taken from the work of Cohen et al. (1991) and 11 current cases were added.
UI - 8859104
AU - Kilmartin DJ; Mooney DJ; Acheson RW; Payne SJ; Maher ER; Eustace P
TI - von Hippel-Lindau disease and familial polyposis coli in the same family.
SO - Arch Ophthalmol 1996 Oct;114(10):1294
AD - Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin 2, Ireland.
UI - 9010867
AU - Traboulsi EI; Apostolides J; Giardiello FM; Krush AJ; Booker SV;
TI - Hamilton SR; Hussels IE Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis.
SO - Ophthalmic Genet 1996 Dec;17(4):167-74
AD - Johns Hopkins Center for Hereditary Eye Diseases, Wilmer Ophthalmological Institute, Baltimore, MD, USA.
BACKGROUND: Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21. The extracolonic manifestations of FAP include pigmented ocular fundus lesions (POFLS), cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. POFLS are present at birth in about 80% of patients with FAP and are excellent clinical congenital markers for the disease. We studied the distribution of POFLS by number and APC mutation in families of the Johns Hopkins Polyposis Registry. MATERIALS AND METHODS: Of the 51 families with FAP, 42 (82%) had an identifiable APC mutation. We correlated the presence/absence and distribution by number of POFLS with the type and location of the mutation in the APC gene in 21 families where an ocular examination had been performed in at least one affected member, and where a systematic search for mutations in the APC gene had been undertaken. Families were considered POFL-positive if the average number of lesions per patient was three or more, or if at least one family member had three or more lesions. RESULTS: Fifteen of the 21 families (71.4%) were POFL-positive. Mutations of the APC gene were detected in 15 of the 21 families. Of these, 12 (80%) were POFL-positive. Families with mutations at condons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations at condons 541, 625, 1055, 1059, 1061, 1230, 1309, 1465, and 1546 (exons 12-15) were POFL-positive. One patient with a mutation at codon 2621 (exon 15) had no POFLS. CONCLUSIONS: Mutations in exons 1-8 and the distal portion of exon 15 of the APC gene are associated with a POFL-negative phenotype, while those in exons 10 to the proximal portion of exon I5 are generally associated with a POFL-positive
UI - 9229577
AU - Giardiello FM
TI - NSAID-induced polyp regression in familial adenomatous polyposis patients.
SO - Gastroenterol Clin North Am 1996 Jun;25(2):349-62
AD - Deparment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
NSAIDs inhibit prostaglandin synthesis. In 1983, Waddell et al first reported that sulindac, a NSAID (Clinoril), caused regression of rectal adenomatous polyps in several patients with familial adenomatous polyposis, an inherited form of colorectal cancer. Subsequently, NSAIDs have been used as chemopreventive agents in animal carcinogenesis models and adenoma regression had been confirmed in human trials with sulindac. This article summarizes these developments and describes possible mechanisms of colorectal neoplasia chemoprevention.
UI - 9152835
AU - DudokdeWit AC; Tibben A; Duivenvoorden HJ; Frets PG; Zoeteweij MW;
TI - Losekoot M; van Haeringen A; Niermeijer MF; Passchier J Psychological distress in applicants for predictive DNA testing for autosomal dominant, heritable, late onset disorders. The Rotterdam/Leiden Genetics Workgroup.
SO - J Med Genet 1997 May;34(5):382-90
AD - Department of Medical Psychology, Erasmus University Rotterdam, The Netherlands.
In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if available, also participated in the study. Distress was measured with the subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk for the neurodegenerative disorders reported more avoidance than those at risk for the cancer syndromes. People at risk for FAP and partners of those at risk for HBOC reported less intrusion than the others at risk and the other partners. Subjects who were more distressed reported more experiences with the disease in close relatives, the disease having a great impact on their lives, having considerations against predictive testing, expecting that being identified as a gene carrier would have adverse effects, and expecting relief after being identified