Role of prophylactic colectomy in Lynch syndrome.
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Colectomy↗
Biomedical subjects
Jane F Lynch
Publications and source records attributed to Jane F Lynch.
Multiple primary cancer, including transitional cell carcinoma of the upper uroepithelial tract in a multigeneration HNPCC family: molecular genetic, diagnostic, and management implications.
OBJECTIVE: We report a multigeneration family where colorectal cancer and cancer of multiple diverse anatomic sites, inclusive of transitional cell carcinoma of the upper uroepithelial tract, were manifested in several relatives. METHODS: A specific pattern of cancer of the colorectum, endometrium, ovary, small bowel, and transitional cell carcinoma, with a vertical distribution of this cancer phenotype through multiple generations, was consonant with a diagnosis of hereditary nonpolyposis colorectal cancer. RESULTS: Germline mutation testing identified the MSH2 mutation, which segregated with the cancer phenotype. This family study clearly demonstrates the value of genetic testing in the management and treatment decision process. CONCLUSIONS: We document, perhaps for the first time, how molecular genetic testing in hereditary nonpolyposis colorectal cancer can aid in the identification of a potential renal transplant donor for a relative with the MSH2 mutation who is experiencing renal insufficiency secondary to transitional cell carcinoma.
Adult↗
Hereditary chronic lymphocytic leukemia: an extended family study and literature review.
Leukemia is manifested in about 1-2% of people in Western industrialized nations. The most common form of leukemia is B-cell chronic lymphocytic leukemia (B-CLL), which accounts for approximately 30% of all cases. While CLL's etiology remains elusive, there is increasing evidence that substantially supports the role of hereditary factors in a subset of cases of this disease. Our purpose is to describe an extremely well documented CLL family wherein the disease has been verified in a father and his four sons; two of the sons are identical twins. The family history, including available medical records and pathology reports, was gathered and reviewed. Peripheral blood lymphocytes were used for cytogenetic and fluorescence in situ hybridization analyses. The family reported herein shows classic findings in support of an autosomal dominant mode of genetic transmission of CLL. Given the explosive developments in molecular genetics during the past decade, it is certain that families of this type will provide important clues to the etiology, pathogenesis, and ultimate prevention of CLL.
Adolescent↗
Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome.
BACKGROUND: Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations. METHODS: Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient. RESULTS: Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation. CONCLUSIONS: The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a "new" putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.
Adult↗
Hereditary factors in pancreatic cancer.
The incidence and the mortality rates for pancreatic cancer are the same, indicating its dismal outlook. Its natural history remains elusive. Cigarette smoking appears to be the most significant environmental culprit. Hereditary factors may account for approximately 5% of the total pancreatic cancer burden. However, when its extant heterogeneity and the reduced penetrance of causal germline mutations are considered, the hereditary incidence may significantly exceed this estimate. Even when endoscopic ultrasound (EUS), the gold standard for pancreatic cancer screening, is utilized, early detection with surgical cure has rarely been accomplished. Needed to ameliorate this problem is research into genetic and environmental risk factors and their interaction. The identification of tumor biomarkers which signal early pathogenetic events, thereby enabling pancreatic cancer to be diagnosed at its earliest possible stage before it has spread to regional lymph nodes or to more distant sites, will improve the outlook. We discuss our research approaches to this problem. Members of families with the p16 germline mutation will undergo EUS coupled with the collection of pancreatic juice for the study of a possible gradient for telomerase activity, K- ras mutations, and cytology. If changes in these putative biomarkers are observed, endoscopic retrograde cholangiopancreatography (ERCP) would be the next diagnostic step. We conclude with a discussion of ethical concerns about this research.
Adenocarcinoma↗
Family with acute myelocytic leukemia, breast, ovarian, and gastrointestinal cancer.
We report a multigeneration family in which hematologic cancers, particularly acute myelocytic leukemia (AML), and solid tumors were interspersed in cancer-prone lineages consistent with an autosomal dominant mode of genetic transmission. This combination of AML and solid tumors, in the absence of a known hereditary disorder such as the Li-Fraumeni syndrome, appears to be unique. This pedigree appears to support our hypothesis of a genetic susceptibility to both solid tumors and hematologic cancer in this kindred. Our study involved the genetic work-up of the family and the education of high-risk patients. Medical and pathology reports were retrieved for cross-referencing and verification of family reports. Blood collected through venipuncture and, when available, diagnostic bone marrow specimens were obtained for cytogenetic studies, inclusive of multiflour fluorescence in situ hybridization (M-FISH) and G-banding methods. Slides and tissue blocks were reviewed, when available. No constitutional chromosomal abnormality or rearrangement and no abnormal platelet count or function was identified in cancer-affected members or high-risk relatives in this family. However, two family members affected with AML exhibited abnormal acquired clones in their bone marrow specimens by both G-band studies and interphase FISH, both with a deletion of 5q.
Bone Marrow↗
Hereditary cancer: family history, diagnosis, molecular genetics, ecogenetics, and management strategies.
The translation of knowledge about hereditary breast cancer and its improved control, as well as prevention through prophylactic surgery, has been significantly accelerated through the veritable explosive discoveries in molecular genetics inclusive of BRCA1 and BRCA2 germline mutations. Needed however, among the physician community, medical geneticists, and genetic counselors, is a raised level of knowledge about hereditary breast cancer syndromes. Particular attention needs to be given to their extant genotypic and phenotypic heterogeneity, their natural history, and foremost, the requirement of a sufficiently detailed family history, with knowledge as to how to interpret its significance so that hereditary cancer syndrome can be diagnosed, should it, in fact, exist in the particular family. Collectively, surveillance and management programs can then be developed for the patient and his or her high-risk relatives. We believe very firmly that this knowledge needs to be extended to the individual patient(s), first- and second-degree relatives so that they can benefit from this knowledge.
Adenomatous Polyposis Coli↗
Challenging pancreatic cancer-prone pedigrees: a nosologic dilemma.
OBJECTIVES: Our objective is to describe 11 pancreatic cancer (PC)-prone families, none of which are consonant with known hereditary cancer syndromes, in an attempt to portray familial aggregations of this disease that might be encountered in a clinical practice setting. METHODS: We selected 11 families containing two or more first- and/or second-degree relatives affected with PC from a registry of 200 PC-prone kindreds. Each proband and/or key relative(s) was interviewed and completed a detailed family history questionnaire (after providing informed consent) that allowed us to extend the pedigree as far as possible with retrieval of primary medical and pathology documents, whenever available. RESULTS: All of the 11 families show PC features that merit clinical attention and raise questions as to whether this familial clustering could be due to "chance" alone, exposure to certain common environmental factors, such as cigarette smoking, and/or polygenic, multifactorial, or Mendelian inherited factors. CONCLUSIONS: It is estimated that about 5% of PC may have a primary hereditary etiology. Because of early death, reduced penetrance, and often profuse phenotypic and genotypic heterogeneity, particularly with respect to variable age of onset and association with diverse patterns of cancer at different anatomic sites, the pedigrees require extension for ultimate diagnosis. Physician knowledge about PC's natural history and syndrome delineation should ultimately foster earlier diagnoses and possibly prevention of this disease. These high-risk patients may provide a source of DNA for formal linkage analysis in the search for culprit cancer-prone susceptibility loci.
Adolescent↗