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Biomedical subjects

J F Lynch

Publications and source records attributed to J F Lynch.

At least 91 records · Page 5Linked to original sources
PubMed1986

Familial heterogeneity of colon cancer risk.

The authors have assembled detailed family histories of cancer on 857 cancer probands, of whom 180 manifested colorectal carcinoma. This study determines if some families had a greater risk for colorectal cancer than others, and if so, what factors were associated with an increase in risk. To test for the possibility of heterogeneity of risk, a parameter called the Z-score, was calculated for each family. The Z-score is a measure of the number of cancer cases in the family adjusted for the number of expected cases. A permutation test was employed to test whether or not the variance of Z-scores from the sample was greater then expected by random chance. The variance for families ascertained through colon cancer probands, but not in any of the other groups, was significantly increased. Of the colon group, 10.6% fell into a high-risk category, as did 5.56% of the rectal cancer families, but only 3.95% of the other groups combined were at high risk. Anatomic sites (in the proband) with the highest Z-score variances were sigmoid and transverse colon, whereas lower variances were seen for cecum and descending colon. Risk status therefore may be partially dependent upon exact anatomic sites within the colon. The effect of proband's age of diagnosis was not significant, but did show the possibility of an effect on heterogeneity of risk for both the younger and older groups.

Age Factors↗
PubMed1986

Genetics and smoking-associated cancers. A study of 485 families.

Cancer risk was evaluated in relatives of 254 consecutively ascertained probands with histologically verified lung cancer, and 231 probands with other smoking-related cancers. Findings disclosed a lack of any strong evidence for increased risk in lung cancer per se when only lung cancer in relatives was considered. Confounding factors, most prominent of which was the effect of cigarette smoking, variation of secular trends, and the heritability of the smoking phenotype itself, tended to obfuscate identification of an inherited effect presenting itself exclusively as lung cancer liability. On the other hand, a significant increase was observed in cancers of all anatomic sites among the relatives of lung cancer probands (P less than 0.001). Most of these neoplastic lesions were not associated with smoking and were not greatly influenced by secular trends. Furthermore, no significant excesses of cancer at all anatomic sites in relatives of probands with other smoking-associated carcinomas were observed. Thus, it may be concluded that the observation of increased risk for cancer at all anatomic sites in relatives of lung cancer probands may be a reflection of an underlying susceptibility to malignancy in these families.

Epidemiologic Methods↗
PubMed1986

Segregation analysis of hereditary nonpolyposis colorectal cancer.

Segregation analysis of eleven families comprising 2762 individuals indicated compatibility of the data with segregation of a major autosomal dominant gene for hereditary nonpolyposis colorectal cancer. It was estimated that between 71% and 79% of the gene carriers were susceptible and had age of onset that was normally distributed with mean about 47 and standard deviation about 10 years. There was a low frequency of sporadic cases at the older ages, a little less than four percent of nongene carriers being affected by age 80. No significant differences were found between the families exhibiting endometrial cancer (cancer family syndrome) and those not exhibiting endometrial cancer (hereditary site-specific nonpolyposis colonic cancer).

Adult↗
PubMed1986

Familial ovarian carcinoma. Clinical nuances.

Familial ovarian carcinoma has been recognized with increased frequency during the past decade commensurate with physician attention to family history. Putative autosomal dominant inheritance of this heterogeneous problem mandates attention to both paternal and maternal lineages. A family with probable paternal transmission of breast/ovarian carcinoma is presented. One family member had findings consonant with papillary serous adenocarcinoma of ovarian origin, which may have arisen directly from extra-ovarian pelvic mesothelium. These and other clinical nuances of familial ovarian carcinoma are discussed in order to aid physicians in understanding the natural history, surveillance, and management of familial ovarian carcinoma.

Adult↗
PubMed1986

Breast cancer genetics in an oncology clinic: 328 consecutive patients.

We have provided intensive medical-genetic follow-up on a previously published cohort of 225 consecutively ascertained patients with verified breast cancer evaluated in our oncology clinic. Similar evaluation was performed on 103 newly ascertained breast cancer patients, giving a total of 328 consecutive patients with verified breast cancer. We believe that this represents one of the most intensive efforts of its type for meticulous documentation of genealogy and cancer of all anatomic sites on a series of breast cancer patients. The results showed that the familial and putative hereditary categories almost doubled among our original 225 breast cancer probands. We conclude that the impact of the host factor component in breast cancer etiology, as reflected in most reports in the literature, suffers from severe underestimation.

Breast Neoplasms↗
PubMed1986

Familial peritoneal ovarian carcinomatosis: a new clinical entity?

A familial form of ovarian carcinoma is now widely recognized. There are at least several ovarian cancer-prone genotypes, consistent with genetic heterogeneity. Prophylactic oophorectomy has been employed for women who were judged to be at 50% risk for this disease by virtue of their position in the pedigree. However, recent evidence has disclosed that a fraction of such patients who underwent prophylactic oophorectomy and who had ovaries which appeared to be histologically normal at surgical resection, subsequently developed intraabdominal carcinomatosis with histologic findings showing the lesions to be indistinguishable from ovarian carcinoma. Given the embryologic derivatives of the ovary, which comprise gonadal ridges composed of mesodermal cells covered by coelomic epithelium, we postulate that patients with hereditary predisposition to ovarian carcinoma harbor the first germinal hit in both the epithelial cells of the ovary as well as their derivatives in the coelomic mesothelium. These patients may then be inordinately susceptible to carcinogenesis from the second (somatic) hit in these same tissues.

Adenocarcinoma, Papillary↗
PubMed1985

Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource.

Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma; and hereditary site-specific colon cancer (HSSCC), or Lynch syndrome I, which shows all of the same characteristics, except for extracolonic cancer. Nine families with CFS and two with HSSCC provided the resource that was tested for biomarkers (see companion article). All families were meticulously evaluated for genealogy and cancer verification. Biologic specimens were obtained during field visits to areas of closest geographic proximity to the families. Cancer education and recommendations for surveillance/management were provided to patients and their physicians. Additionally, 40 families (about 3000 individuals) with either CFS or HSSCC have been ascertained. Syndrome cancers were restricted to direct-line relatives as opposed to nonbloodline relatives, arguing against involvement of environmental factors. One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds. This has important clinical significance in that it clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers.

Adolescent↗
PubMed1985

Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies.

Nine families with the cancer family syndrome (CFS), or Lynch syndrome II, and two with hereditary site-specific colonic cancer (HSSCC), or Lynch syndrome I, were investigated for the following potential biomarkers of genotype status: in vitro tetraploidy of dermal fibroblast monolayer cultures; tritiated thymidine uptake (3HdThd) labeling of colonic mucosa; cytogenetics of peripheral blood mononuclear leukocytes; quantitative serum immunoglobulin determinations; methionine dependence in dermal fibroblasts in tissue culture; segregation analysis; and the study of gene linkage with respect to 25 landmark serum and blood group markers. Positive lod scores of 3.19 for linkage of the Jk (Kidd blood group) with CFS were obtained. Both in vitro tetraploidy and 3HdThd uptake in the distal colonic mucosal crypt compartments were positively associated with cancer risk status in CFS and HSSCC kindreds. There was a high incidence of polymorphisms of centromeric heterochromatin, including complete inversion. These findings are of particular clinical and genetic significance because HNPCC lacks premonitory signs of cancer risk. If confirmed, they could conceivably enable definition of genotype as early as birth in members of HNPCC kindreds, thereby enabling psychologic preparation and intensive cancer education for improved compliance in surveillance/management programs. These studies also provide new clues about the chromosome(s) bearing the presumed cancer gene(s). For example, CFS gene(s) may possibly be located on chromosome 2, where Jk is located. These biomarkers merit intensive study in additional HNPCC kindreds for a more complete assessment of their sensitivity and specificity. Additionally, essential aspects of previous reports involving biologic samples from these and/or similar subject kindreds are included to permit a comprehensive presentation of the combined findings of this consortium to date.

Colon↗
PubMed1985

Cancer genes, multiple primary cancer, and von Hippel-Lindau disease.

Von Hippel-Lindau disease is inherited by an autosomal dominant gene that may show marked expressive variability of cancer phenotype in certain patients/families. We describe a patient with a strongly positive family history of this disease who, at age 28, underwent craniotomy with removal of a cystic cerebellar hemangioblastoma; at age 48, he developed syringomyelia of the spinal cord, became quadriplegic, and had a progressive downhill course. At autopsy, hemangioblastomas of the cerebellum and spinal cord were found, as well as a left renal cell carcinoma, an oat cell carcinoma of the lung, a hepatocellular carcinoma, and an atypical thyroid adenoma. This tumor spectrum appears to be unique, although chance cannot be excluded. It is possible, however, that these findings might represent an expression of the deleterious genotype that became evident because of this patient's prolonged survival from his initial cerebellar hemangioblastoma.

Adult↗
PubMed1985

Hereditary ovarian carcinoma. Biomarker studies.

Three ovarian-cancer-prone kindreds were studied, two of which contained identical twin sisters concordant for ovarian carcinoma. In one kindred, both identical twin sisters had daughters with ovarian carcinoma. In another kindred, one of the identical twin sisters had an ovarian-cancer-affected daughter. Ovarian carcinoma showed vertical transmission in all three families in a pattern consonant with an autosomal dominant mode of inheritance. Medical-genetic survey of each family included detailed questionnaires with retrieval of primary medical and pathology documents on cancer of all anatomic sites. Putative biomarker determinations included: (1) in vitro hyperdiploidy in dermal monolayer cultures; and (2) lower serum levels of alpha-L-fucosidase (less than or equal to 275 IU/ml) in all cancer-affected patients and statistically significant lower levels in 50% risk individuals when compared to spouse and published controls (P = 0.04 and P = 0.0002, respectively). These findings are discussed in context with the eventual development of a risk factor profile which, given acceptable sensitivity and specificity, would enable identification of individuals who would be prime candidates for intensive surveillance/management programs.

Adult↗
PubMed1985

The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited. Childhood cancer.

We studied two children who had rhabdomyosarcoma and glioblastoma and who were from a family with a hereditary cancer syndrome that was characterized by sarcoma, breast cancer, brain tumors, lung cancer, laryngeal carcinoma, leukemia, and adrenocortical carcinoma. The deleterious genotype has now been expressed through the fourth generation of this large kindred. The pedigree emphasizes the need for an extended history of several generations to arrive at a hereditary-syndrome diagnosis. A limited pedigree may result in nonappreciation of the genetic component. The pedigree illustrates that, in certain circumstances, the highly specific varieties of cancer may occur in children before it is expressed in the parent who carries the putative gene. Pediatricians, in evaluating the causes of childhood cancer, must be cognizant of cancer among adult relatives, since this recognition may aid in the diagnosis of those hereditary cancer syndromes that are characterized by cancer occurrence in children as well as adults.

Adrenal Cortex Neoplasms↗
PubMed1985

Colorectal cancer in a nuclear family. Familial or hereditary?

Because of the high incidence of colorectal cancer, familial aggregations of this disease are common. Differentiation between etiologies contributing to familial clustering (which may have resulted either from common environmental exposure or from mere chance) and primary genetic factors may prove vexing to the physician. This report deals with the myriad problems encountered when attempting to make such etiologic distinctions in order to provide appropriate surveillance and management, based upon tumor spectrum and natural history, for patients at increased cancer risk.

Aged↗
PubMed1985

Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II): a common genotype linked to oncogenes?

We hypothesize that: hereditary nonpolyposis colorectal cancer (HNPCC) accounts for a significant proportion of the colon cancer burden; the premalignant colonic mucosa in HNPCC patients may be comparable in many respects to the premalignant polyps in its hereditary multiple adenomatous polyposis counterpart; and finally, study of HNPCC colonic mucosa may harbor important clues for elucidation of the multistep process of carcinogenesis, including relationships between activated oncogenes, genetics, and environmental perturbations.

Adenoma↗