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Biomedical subjects

J F Lynch

Publications and source records attributed to J F Lynch.

At least 73 records · Page 4Linked to original sources
PubMed1990

Heterogeneity and natural history of hereditary breast cancer. Surgical implications.

The properly compiled cancer family history can prove to be one of the most cost-effective and powerful instruments for cancer control in breast cancer. Needed, however, is an understanding of the heterogeneity of hereditary breast cancer and knowledge of those facets of its natural history that can expedite a syndrome diagnosis. Priority concerns for cancer control in hereditary breast cancer are the development of registries of cancer-prone families, willingness by third-party carriers to help defray the costs of surveillance, and more research in molecular genetics.

Breast Neoplasms↗
PubMed1990

SBLA syndrome revisited.

We have provided an in-depth, longitudinal, clinical/genetic/pathologic investigation of a family consonant with the sarcoma, breast cancer and brain tumors, lung and laryngeal cancer, leukemia, lymphoma, and adrenalcortical carcinoma syndrome. The pattern of cancer expression involves all three germinal layers with transmission through multiple generations. Segregation of these cancers occur in a manner consonant with an autosomal dominant mode of genetic transmission. It is hoped that recognition of the significance of this tumor pattern within families will provide an impetus for cancer surveillance, control, and laboratory research in the quest for clues to biomarkers which correlate with its cancer-prone genotype.

Adolescent↗
PubMed1990

Familial pancreatic cancer: clinicopathologic study of 18 nuclear families.

Host factors have been given scant attention in the search for etiology in pancreatic cancer. Several anecdotal reports have identified its familial clustering, whereas a recent population-based case/control study has shown that 6.7% of cases and 0.7% of controls had positive family histories of this disease (p less than 0.001). Forty-seven individuals with pancreatic cancer from 18 families were identified from a review of the medical records of all kindreds on file at our Hereditary Cancer Institute. The observed sex ratio, age of onset, histologic type, and survival were comparable to published data on unselected patients. We did not identify any pattern of extra-pancreatic cancer association. A serious limitation of our study is its lack of a population-based case/control design. Whereas our data are primarily descriptive, they do indicate the need to learn more about the role of familial factors in the etiology of pancreatic cancer. Pancreatic cancer is increasing in incidence, and its prognosis is almost uniformly dismal; identification of persons at high risk may improve cancer control.

Aged↗
PubMed1989

Adenocarcinoma of the small bowel in lynch syndrome II.

Adenocarcinoma of the small bowel is rare and accounts for about 1% of all gastrointestinal tract cancer. This disorder has been identified in association with Crohn's disease, celiac disease, Peutz-Jegher's syndrome, and familial adenomatous polyposis. We report adenocarcinoma of the small bowel in nine patients from eight Lynch syndrome II extended pedigrees. Each affected patient was in the direct genetic lineage or manifested multiple primary cancers (stomach, colon, endometrium, and ovary) consonant with the tumor spectrum of Lynch syndrome II. The average age of onset for small bowel cancer was 47 years (range 31 to 56 years), versus the general population peak occurrence after the sixth decade. We conclude that small bowel cancer may be an integral component of the tumor spectrum of Lynch syndrome II.

Adenocarcinoma↗
PubMed1989

Epidemiology and risk factors.

HBC is common, accounting for approximately 9% of the total breast cancer burden. Given 142,000 cases of breast cancer expected to occur in 1989, this would represent 12,780 cases of HBC patients. Soberingly, each patient represents a family with a variable number of inordinately high risk patients. HBC's natural history is distinctive and enables the identification of at risk patients who can benefit from highly targeted surveillance/management strategies. High priority must be given to development of biomarkers that will one day be found to have acceptable sensitivity and specificity to genotype status. Thus, we would then be able to tell which of the first-degree relatives of affected members have inherited the deleterious gene. This would result in a significant saving of time and money that would otherwise be expended through intensive surveillance strategies. We need cost-benefit research to induce third party carriers to defray expenses for surveillance. Finally, priority attention must be given to biomolecular research for identification of markers of acceptable sensitivity and specificity to the cancer-prone genotype. Eventual cloning of the deleterious gene(s) could lead to knowledge about its chemical and physiologic products, thereby enabling anticancer pharmacologic research. The reward could then be improved control and even prevention of breast cancer, and possibly of the associated cancers in heterogenous forms of this disease.

Adult↗
PubMed1988

Laryngeal carcinoma in a Lynch syndrome II kindred.

Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for about 4% to 6% of the total colorectal cancer burden. It is subdivided into Lynch syndrome I and II. Lynch syndrome I is characterized by an autosomal dominant inheritance pattern for site-specific, early onset, adenocarcinoma of the colon, with proximal predominance and an excess of synchronous and metachronous colonic cancers. Lynch syndrome II (cancer family syndrome) shows these same colon cancer characteristics, but differs in that there is an excess proclivity of other forms of cancer, particularly of the endometrium and ovary. This article documents a family that shows features of Lynch syndrome II. Unique aspects pertain to a patient who is in the direct genetic lineage (whose five brothers manifested colonic cancer), but who developed carcinoma of the uterine cervix at age 34 and laryngeal cancer at 60. The pedigree also shows uterine cervical carcinoma among other patients at genetic risk. Her son, who is a nonsmoker and nondrinker, manifested laryngeal cancer at age 31. These observations appear to add new information about tumor heterogeneity in HNPCC.

Adenocarcinoma↗
PubMed1988

Flat adenomas in a colon cancer-prone kindred.

We describe new pathologic findings in a hereditary nonpolyposis colorectal cancer family. Affected family members developed multiple small adenomas with right-sided predominance; many adenomas had an unusual appearance featuring slightly elevated lesions with adenomatous changes confined to the upper regions of the colonic crypts. We have adopted the previously established term "flat adenoma" for these lesions. This phenotype may be a morphologic marker for at least one subset of hereditary nonpolyposis colorectal cancer.

Adenoma↗
PubMed1988

Age-of-onset heterogeneity in hereditary breast cancer: minimal clues for diagnosis.

Knowledge of the family history of cancer may significantly influence diagnosis and surgical management. Hereditary breast cancer (HBC) is common and accounts for approximately 9% of the total breast cancer burden. The pattern of HBC's natural history, including age of onset, increased incidence of bilaterality, integral tumor combinations in certain kindreds, and vertical transmission consonant with an autosomal dominantly inherited factor, when observed in context with the family history, enables pattern recognition so that the diagnosis might be facilitated. We describe seven families from our Hereditary Cancer Consultation Center (HCCC) and the Creighton Oncology Clinic which are noteworthy for extraordinarily early age of onset. This appears to be an additional example of heterogeneity in HBC and may represent the first account of this remarkable subset. The manner in which age of onset can be incorporated with other aspects of natural history for expediting diagnosis is discussed.

Age Factors↗
PubMed1988

Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II).

Approximately 5 to 6 percent of the total colorectal cancer burden is accounted for by hereditary nonpolyposis colorectal cancer (HNPCC). Because clinical premonitory signs such as those seen in familial polyposis coli (FPC) are lacking, the clinician must recognize clinical findings and family history typical of HNPCC. The authors have described colorectal cancer expression from a survey of ten HNPCC kindreds. Kindred members with colorectal cancer differed significantly (P less than .05) from patients with sporadic colorectal cancer: 1) mean age of initial colon cancer diagnosis was 44.6 years; 2) 72.3 percent of first colon cancers were located in the right colon, and only 25 percent were in the sigmoid colon and rectum; 3) 18.1 percent had synchronous colon cancers; and 4) 24.2 percent developed metachronous colon cancer, with a risk for metachronous lesions in ten years of 40 percent. Affecteds and their first-degree relatives should undergo early intensive education and surveillance. In families with an early age of onset, colonoscopy should begin at age 25, and biannually thereafter, with fecal occult blood testing of the stool semiannually. Third-party carriers must become more responsive to the costly surveillance measures required for these otherwise healthy patients.

Adult↗
PubMed1988

Differential diagnosis of hereditary nonpolyposis colorectal cancer (Lynch syndrome I and Lynch syndrome II).

Increasing recognition of the statistical burden posed by HNPCC (5 to 6 percent of all colorectal cancer) mandates that physicians have a better understanding of the genetics, natural history, and distinction between the hereditary site-specific variant (Lynch syndrome I) and the Cancer Family Syndrome (Lynch syndrome II). The authors report detailed cancer (all sites) family histories on two prototype families with Lynch syndrome I (Family R) and Lynch syndrome II (Family N), which have been under investigation for more than two decades. Emphasis is placed on shared clinicogenetic features; namely, early age of onset of colonic cancer (approximately age 44), multiple primary colonic cancer (24 percent of cases showed metachronous colonic cancer), predominance of proximal colonic cancer location (approximately 65 percent in the proximal colon), and vertical transmission consonant with an autosomal dominantly inherited factor. An increased predilection for extracolonic cancer, particularly endometrial carcinoma, occurs in Lynch syndrome II and is the primary basis for distinction from Lynch syndrome I. Surveillance and management programs must be wholly responsive to these natural history features.

Adult↗
PubMed1988

Breast cancer diagnosis in a putative obligate gene carrier. A family study.

Hereditary breast cancer is common and accounts for about 8% of all breast cancer. It has a distinctive natural history characterized by early age of onset, excess bilaterality, and vertical transmission consonant with an autosomal dominant inheritance pattern. We describe an informative kindred wherein this knowledge was effectively applied, with resultant high yield: early breast cancer diagnosis in a mother who was a putative obligate gene carrier, and a contralateral breast cancer diagnosis in her daughter. A more intensive stance on breast cancer diagnosis must be employed in members of hereditary breast cancer kindreds who are judged to be at inordinately increased risk. Breast cancer control through application of genetic knowledge is readily achievable in the clinical practice setting.

Adult↗
PubMed1988

Hereditary nonpolyposis colorectal cancer--Lynch syndromes I and II.

HNPCC is an autosomal dominantly inherited disorder with proclivity to early onset colorectal cancer in the absence of multiple polyps of the colon. There is a predilection for proximal colonic location (70 per cent) and an excess of synchronous and metachronous colorectal cancers. HNPCC is subdivided into Lynch syndrome I, which is restricted to site-specific colon cancer susceptibility, and Lynch syndrome II, which shows all of the features of Lynch syndrome I, but in addition, patients are at inordinately increased risk for carcinoma of the endometrium, ovary, and other anatomic sites. The frequency of HNPCC is conservatively estimated to be 4 to 6 per cent of the total colorectal cancer burden. Because of the fact that the family history is underreported almost uniformly in medical practice, we believe that the true frequency of this disease may be much greater. Heterogeneity may be extant with respect to tumor association, in that in certain Lynch syndrome II kindreds, carcinoma of the pancreas, kidney, breast, and other anatomic sites may predominate. Knowledge of the natural history of HNPCC predicates surveillance and management strategies. Thus, because of the early onset of and proximal predilection for colorectal cancer, we recommend initiation of colonscopy at age 25 and annually thereafter. We also recommend guaiac testing of the stool at least twice a year. In the case of Lynch syndrome II, in addition to colonscopy, we recommend intensive surveillance for the endometrium, including aspiration biopsies. Other targeted organs, depending on the tumor spectrum in the family, should be given priority attention. Because of an excess of synchronous and metachronous colorectal cancer in HNPCC, subtotal colectomy with ileorectal anastomosis is the treatment of choice for initial colorectal cancer. In women presenting with initial colorectal cancer who have completed their families, consideration should be given to prophylactic hysterectomy and bilateral salpingo-oophorectomy at the time of surgery for colorectal cancer. Needed are biomarkers of acceptable sensitivity and specificity for the genotype, because HNPCC lacks premonitory physical signs. We believe that increased knowledge about colorectal cancer etiology and carcinogenesis can be attained through the study of families prone to the Lynch syndromes.

Adult↗
PubMed1988

Tumor variation in three extended Lynch syndrome II kindreds.

Lynch syndrome II is characterized by an autosomal dominantly inherited susceptibility to early onset colon cancer with proximal predominance, an excess of synchronous and metachronous colonic cancer, carcinoma of the endometrium, ovary, and multiple primary cancer excess. Knowledge of the full tumor spectrum in this disorder(s) remains elusive. Cancers that are uncommon in this disease, but present in three extended Lynch syndrome II families, included brain tumors, carcinoma of the bile duct, duodenum, the urological system, and breasts. Long-term followup of these families (as long as two decades) provided the opportunity to trace in depth this tumor spectrum. Full scrutiny of cancer of all anatomic sites in the absence of biomarkers of high sensitivity and specificity to the cancer-prone genotype will be necessary to comprehend more clearly whether these (or other) cancer sites are integral to this disorder, whether common environmental exposures are involved and, finally, whether chance can explain these cancer associations.

Adolescent↗
PubMed1987

alpha-L-fucosidase variant and lipid-associated sialic acid in hereditary ovarian cancer.

In a previous study of alpha-L-fucosidase (ALF) activities in plasma samples from three ovarian cancer-prone kindreds, we observed a significant inverse correlation of cancer susceptibility and enzyme activity. Because a low level of plasma ALF activity is an inherited characteristic that has been termed the "fucosidase variant," the above demonstration has provoked great interest in the fucosidase variant relative to the genetic transmission of ovarian cancer susceptibility. We have now observed in these same plasma samples that the concentrations of lipid-associated sialic acid (LAS) are also inversely correlated with the ALF activities and, therefore, directly correlated with ovarian cancer susceptibility. In the fucosidase variant individual, the ALF is modified intracellularly, but the modified enzyme only exhibits decreased activity in the plasma. For this reason, ALF cannot be involved in tumorigenesis. Rather, the factor that modifies ALF is probably involved and is the inherited character. Therefore, we hypothesize that this modifier is responsible not only for the "fucosidase variant" but also for the elevated concentration of LAS and plays a role in hereditary ovarian cancer.

Adolescent↗
PubMed1987

Familial bladder cancer in an oncology clinic.

We have evaluated family history and cigarette smoking history on 49 consecutively ascertained patients with urinary bladder carcinoma and compared them with 956 consecutively ascertained patients with histologically verified cancer (all sites), all of whom were being treated in the same oncology clinics. Data was collected through interviews, questionnaires, and primary medical and pathology documents. Cancer risks were compared on the basis of anatomic sites involved and with cumulative risk estimated from data in the Third National Cancer Survey. A permutation test was also employed. Significant heterogeneity of risk (z = 4.85, p less than or equal to 0.02) for bladder cancer was found in relatives of probands with bladder cancer. Significant heterogeneity or increase in risk of bladder cancer was not observed when families with lung, other smoking related cancer, and nonsmoking related cancer were analyzed. Though based on a limited number of verified bladder cancer patients, we have provided statistical evidence in support of our hypothesis that bladder cancer may have a stronger familial etiologic component than heretofore recognized.

Humans↗
PubMed1987

Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II).

Primary genetic factors are etiologic in at least 5-10% of patients with colon cancer. The polyposis syndromes (FPC) are easily identified examples because of the spectacular number of polyps. The hereditary nonpolyposis syndromes (HNPCC), although five times more common than FPC, are usually not recognized because they do not have such a distinctive clinical, premonitory genetic marker. Colorectal cancer expression was surveyed in 10 extended, thoroughly documented HNPCC kindreds. One hundred sixteen patients were found to have 183 colorectal cancers. Despite the striking family history, less than 5% were correctly treated by subtotal colectomy. This provided a unique opportunity to study the natural history. Five findings differed significantly (p less than 0.05) from patients with sporadic colon cancer: (1) mean age of initial colon cancer diagnosed was 45.6 years; (2) 69.1% of first colon cancers were located proximal to the splenic flexure of the colon; (3) 18.1% had synchronous colon cancer; (4) 24.2% had metachronous colon cancer develop with life table analysis showing the risk for a metachronous lesion at 10 years to be 40%; and (5) only 23.3% of cancers were located in the sigmoid colon or rectum. Based on this data, it is recommended that the family history of all patients with a newly diagnosed colon cancer be evaluated for evidence of this syndrome. If an autosomal dominant inheritance pattern emerges, an in-depth genetic investigation is indicated. When HNPCC is confirmed, the following recommendations apply: a subtotal abdominal colectomy is indicated at the time of the initial colon cancer because of the risk of synchronous and metachronous lesions. The rectum should be spared in favor of careful lifetime surveillance because of the proclivity for proximal colon cancer involvement. As yet unaffected members of a newly diagnosed HNPCC kindred who are in the "direct genetic line" should be cautioned that they are at 50% risk and must begin an intensive surveillance program beginning in the third decade with careful attention to the right colon. Patients from newly diagnosed HNPCC families who have had a previous conventional colectomy for colon cancer should, at the very least, enter an intensive surveillance program; a prophylactic completion subtotal colectomy should be considered for patients who are less than totally compliant.

Adolescent↗