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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 1 (1988), S. 0 
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Familial atypical multiple mole melanoma (FAMMM) syndrome, a cancer-associated genodermatosis, is a dominantly inherited heterogeneous disorder with variable expressivity of both its cutaneous and cancer phenotypes. By using a verified historical review technique of cancer documentation (idout patient health records, pathology reports/slides, autopsy reports/slides, and death certificates) of all anatomic sites in all members of a modified nuclear pedigree (first-degree relatives plus maternal and paternal grandparents, aunts, and uncles) over several generations, we showed that the FAMMM syndrome is similar to the majority of autosomal dominant inherited cancer-associated genodermatoses and has excessive risk for cancer of multiple anatomic sites. With respect to the FAMMM syndrome, these cancers involved the breast, respiratory tract, gastrointestinal system, the eye (intraocular melanoma), and the lymphatic system. These FAMMM pedigrees showed some of the following distinctive characteristics of hereditary cancer: 1) integral patterns of cancer within and between pedigrees; 2) early age of onset of cancer; 3) prolonged survival of some pedigree members with cancer; and 4) an excess of multiple primary melanomas and cancers of variable anatomic sites. The presence of these features indicates that these cancers of variable anatomic sites may be etiologically associated with the FAMMM syndrome. Heterogeneity should be investigated in FAMMM pedigrees with attention to consistent differences in size and distribution of atypical lesions, age at cancer onset, and pattern of tumor occurrences. The occurrence of FAMMM pedigrees in the general population or among pedigrees of probands with atypical nevi is not known. The occurrence of systemic cancers in these FAMMM pedigrees requires the development of cancer surveillance programs that are specifically modified to the particular cancer pattern of each pedigree.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Hereditary non–polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer and linked to germline defects in at least four mismatch repair genes. Although much has been learned about the molecular pathogenesis of this disease, ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 1 (1995), S. 298-300 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Hodgkin's disease (HD) is poorly understood. Its aetiology is complex, with a layering of environmental and genetic causes. This disorder (or disorders) clusters bimodally in young and old adults. A proposed environmental factor in the younger-onset form has been a childhood infectious agent, ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] DNA mismatch repair is important because of its role in maintaining genomic integrity and its association with hereditary non-polyposis colon cancer (HNPCC). To identify new human mismatch repair proteins, we probed nuclear extracts with the conserved carboxy-terminal MLH1 interaction domain. ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 768 (1995), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1530-0358
    Keywords: Desmoids ; Genetics ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to describe the natural history and management of surgically unresectable intra-abdominal desmoid tumors in two patients with Gardner's syndrome from two unrelated families, where each had failed on conventional therapy. METHODS: Two patients with Gardner's syndrome were placed on a chemotherapy regimen which included doxorubicin (90 mg/m2) and dacarbazine (900 mg/m2) in divided doses over four days of continuous infusion. Their progress on chemotherapy was assessed by abdominal computerized tomography and laparoscopy. RESULTS: The computerized abdominal tomography scans proved difficult to interpret because of adhesions and matted small bowel resulting from the patients original colectomies. These findings made it difficult to differentiate postoperative changes from residual desmoid tumor. Second-look laparotomy in such patients was contraindicated as this may predispose to further desmoid production. Laparoscopy disclosed a complete response to this chemotherapy. Nevertheless, we had an iatrogenic small bowel perforation in one of these patients. Each patient showed a complete response to chemotherapy. CONCLUSION: Surgical resection remains the first-line treatment of intra-abdominal desmoid tumors. However, doxorubicin/ dacarbazine chemotherapy on a clinical trial basis may be indicated in patients whose intra-abdominal desmoid is unresectable, or who have failed to respond to treatment with hormones (tamoxifen, Toremifene), steroids (prednisone), and nonsteroidal anti-inflammatory agents (Clinoril®; Merck & Co., Inc., West Point, PA).
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 39 (1996), S. 109-110 
    ISSN: 1530-0358
    Keywords: HNPCC ; Prophylactic subtotal colectomy ; Germline carriers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1530-0358
    Keywords: Suspected hereditary nonpolyposis colorectal cancer ; Germline mutations ; Mismatch repair genes ; Genetic testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (〈40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged 〈50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged 〈50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1530-0358
    Keywords: Breast neoplasms, genetics ; Breast neoplasms, mortality ; Genes, BRCA1, genetics ; Colorectal neoplasms, genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study compared characteristics of colorectal cancer between families with dominant breast cancer inheritance and the general population. The cumulative incidence of colorectal cancer was also studied in genetically determined breast cancer syndrome subjects with BRCA1 and BRCA2 mutations and compared with the general population. METHODS: Subjects included 42 patients with colorectal cancer from 32 clinically determined hereditary breast cancer kindreds based on the autosomal dominant inheritance of breast cancers and early age of onset. The general population colorectal cancer cohort was composed of 755 patients from a tumor registry. Lifetime risk of colorectal cancer was determined in 164 BRCA1 and 88 BRCA2 gene mutation carriers and compared with the general population. Mean age of colorectal cancer onset, anatomic site distribution, histologic stage at presentation, and five year stage-stratified survival rates were compared between clinically determined hereditary breast cancer family members and the general population. RESULTS: The lifetime risk of colorectal cancer in male BRCA1 and BRCA2 mutation carriers was 5.6 percent, which was not different from 6 percent in males from the general population. Likewise, the lifetime colorectal cancer risk in female BRCA1 and BRCA2 mutation carriers was 3.2 percent, which was not different from 5.9 percent in females from the general population. Mean age of onset ± standard error for patients with colorectal cancer was 60±2 years for hereditary breast cancer kindreds compared with 67±0.4 years for the general population (P=0.0004). Colorectal cancer site distribution did not vary between hereditary breast cancer and the general population. Overall colorectal cancer stage distribution was significantly different, with more Stage I and fewer Stage IV cancers in subjects with hereditary breast cancer compared with the general population (P=0.01). Overall five year stage-stratified colorectal cancer survival rate ± standard error was 66±8 percent for hereditary breast cancer kindreds and 46±2 percent for the general population (P=0.023). CONCLUSION: Lifetime cumulative colorectal cancer incidence in subjects with BRCA1 and BRCA2 gene mutations was not different from the general population. However, significant differences in colorectal cancer were noted between hereditary breast cancer family members and the general population. Hereditary breast cancer-associated colorectal cancer had an earlier age of onset, lower tumor stage, and better survival rate than the general population. Except for age of onset, colorectal cancer in hereditary breast cancer kindreds exhibited more favorable characteristics than colorectal cancer in the general population.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 36 (1993), S. 254-260 
    ISSN: 1530-0358
    Keywords: Lynch syndromes ; Natural history ; Cancer genetic diagnosis ; Cancer Control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Lynch syndromes account for about 4 to 6 percent of the total colorectal cancer (CRC) burden. Despite more than two decades of documentation in the literature, many physicians fail to recognize the clinical features of these syndromes. The lack of premonitory physical stigmata, coupled with the absence of a biomarker of cancer susceptibility, mandates full reliance on a well-orchestrated family history for diagnosis. These deficiencies impede cancer control. Even if the diagnosis is made, proper surveillance and management measures that are responsive to the Lynch syndromes' natural history may fail to be implemented. We describe CRC occurrences in patients from four extended Lynch syndrome kindreds. Failures in cancer control were attributable to poor patient compliance and/or to limited physician knowledge about the natural history and surveillance recommendations for the Lynch syndromes. Physicians need to more effectively educate their high-risk patients about the significance of genetic risk, the natural history of CRC, and the appropriate surveillance strategies in the Lynch syndromes.
    Type of Medium: Electronic Resource
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