Search PubMed⌕ Search

Biomedical subjects

L C Strong

Publications and source records attributed to L C Strong.

At least 91 records · Page 5Linked to original sources
PubMed1987

The genetic implications of long-term survival of childhood cancer. A conceptual framework.

This article outlines a conceptual framework for considering the genetic implications of childhood cancer and taking into account genetic predisposition as well as the genotoxic effects of cancer treatment. The primary consequences by which genetic effects are measured are somatic genetic damage, second tumors in the proband, germline genetic damage, and reproductive outcomes. Studies of retinoblastoma and rhabdomyosarcoma are offered as models for examining the etiology of genetic effects and defining the risks for a second malignant neoplasm. The conclusion from these studies is that there is a small subgroup of patients for whom the genetic implications of long-term survival are significant. Characteristics of this subgroup and the risks involved in treatment are defined. More optimistically, the data indicate that for the majority of patients, the risks involved in mutagenic and carcinogenic agents used in the treatment of childhood cancer are small. The authors conclude that treatment-related effects vary according to the genetic background of the proband.

Adolescent↗
PubMed1987

Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors.

A series of gene probes for chromosome 11 has been used to study the genetic events associated with the development of Wilms tumor. Examination of DNA samples from five patients with Wilms tumor in whom the tumors showed loss of chromosome 11 alleles and their parents indicate that alleles lost in the tumors are of maternal origin. These data suggest that the parental derivation of chromosome 11 alleles lost in these Wilms tumors is not random.

Alleles↗
PubMed1987

Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor.

Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop.

Child↗
PubMed1987

Cancer in survivors of childhood soft tissue sarcoma and their relatives.

One hundred fifty-nine 3-year survivors of childhood soft tissue sarcoma and their relatives were surveyed to determine the frequency of second malignant neoplasms (SMNs) in patients and cancer in their relatives. The cancer experience of the patients, their offspring, siblings, parents, parental siblings, and grandparents was compared to that expected of the general population based on age-, sex- and calendar year-specific rates from the Connecticut Tumor Registry. A significant excess of SMNs was observed in the patients (observed expected = 8:0.38). Among 758 first-degree relatives, a significant cancer excess was observed (34:20.68), attributable largely to cancer of soft tissue and bone (6:0.44) and breast (9:3.39) and to cancers occurring before age 35 years (12:4.14). Overall, a significantly lower than expected cancer incidence was confirmed in the 1,693 second-degree relatives (142:178). To identify patient characteristics associated with higher than expected familial cancer risk, kindreds were partitioned by patient age at diagnosis tumor type, tumor site SMN and other factors. A highly significant cancer excess was observed in the relatives of SMN patients (26:12.78). The tumor types occurring in excess in close relatives were also observed as SMNs in the patients. The findings confirm an association among childhood soft tissue sarcoma and cancers of the breast, bone, joint, or soft tissue as SMN in patients and in close relatives and suggest that the risk of a second tumor is associated with a familial predisposition to cancer.

Adolescent↗
PubMed1986

Familial aggregation of cancer in Laredo, Texas: a generally low-risk Mexican-American population.

Genealogies for the Mexican-American city of Laredo, Texas, have been assembled by computer from individual civil and church records of birth, marriage, and death. Documentation is available on vital events in the lives of over 300,000 individuals, about 80% of the city population from 1870-1981. These data were collected to determine the degree to which death from cancer is more clustered in families than would be expected by chance alone; methods specific to this data base have been developed to accomplish this task. A statistically significant excess of familial cancer was observed overall when all cancer sites were pooled, but no evidence was observed for excess familial risk at single sites except for breast cancer and perhaps for ovarian cancer. The excess of breast cancer risk is comparable to that observed in other populations. A few site-combinations manifest excess familial risk, most notably those involving and dominated by breast cancer and certain digestive system sites. We do not confirm the degree of familiarity observed elsewhere for cancers of the lung, colorectum, stomach, or other sites in this generally low-risk population. Even where we find evidence of excess risk, the degree of excess is small and the number of multiply affected families too small to test etiologic models by segregation analysis. The absence of excess familial risk does not appear to be due to inadequate numbers of cases, since breast cancer is familial with no more occurrences in Laredo than other sites. These results differ to some extent from those found in a similar study of Utah Mormons, but it is unclear whether this is because of differences in risk patterns or statistical properties of the analytic methods used in the two studies.

Adolescent↗
PubMed1984

Aggregation of colon cancer in family data.

Although only a small proportion of common cancers show familial aggregation, studying such families can elucidate the roles of shared environment and genes in the development of neoplasia. We report an analysis of nine colon cancer pedigrees using new nonparametric objective methods to measure familial aggregation as a means of determining the existence of heterogeneity in the data. Each family was selected through a proband with nonpolyposis colon cancer who had a first-degree relative with documented colon cancer. To assess the aggregation of different cancers in these families we employ a method which evaluates both excess number of cases as well as distribution by risk in family members. We find that eight of the nine families exhibit significant aggregation of colon cancer: endometrial cancer aggregates in three families, breast in none, kidney in one, and all sites in eight. In this way, we show that two families fit the criteria for Cancer Family Syndrome, and that one is not a high-risk cancer family.

Biometry↗
PubMed1984

A method to detect excess risk of disease in structured data: cancer in relatives of retinoblastoma patients.

It is often of interest to know whether there is increased occurrence of a trait in a pedigree or other structured set of epidemiological data. In answering such questions most current methods use aggregate measures, such as relative risk, that may not relate the outcome for each individual to that individual's risk. In this paper we present a simple method, and its computational algorithm, to overcome this limitation. This new method also permits one to identify high-risk families or subsets of a collection of data, which is not always possible using other approaches. In a study of cancer risk among relatives of retinoblastoma patients, by applying this new method it was found that 11 of 33 families each obtained through a unilateral retinoblastoma patient are at statistically high risk of cancer at all sites combined, while there are 15 of 47 such families obtained through a bilaterally affected proband. These results are unlikely to have occurred by chance, indicating an overall excess risk in the ancestors of these retinoblastoma cases. The proposed test procedure does not specify the cause of elevated risk; however, a method is proposed that provides some indication regarding possible causal mechanisms under some circumstances.

Biometry↗
PubMed1984

Cancer mortality in relatives of retinoblastoma patients.

The risk of other cancers in relatives of retinoblastoma (RTB) patients was determined by a survey of the mortality experience of siblings, parents, parental siblings, and grandparents of all U.S. or Canadian RTB patients referred to The University of Texas M.D. Anderson Hospital and Tumor Institute between 1944 and 1980. Expected mortality was ascertained by the application of age-, sex-, race-, and calendar year-specific U.S. mortality rates to the observed person-years. Among 607 relatives of 33 unilateral-sporadic RTB probands, no excess in cancer deaths was observed (observed/expected = 18/22). Among 733 relatives of 47 bilateral-familial RTB probands, a slight excess in cancer deaths was observed (41/31). A significant excess in cancer deaths was occurred in relatives under age 55 years (18/9) and in fathers (7/1) of the bilateral RTB probands. To determine whether the cancer excess was related to some unique allele associated with second tumors in RTB survivors, the cancer mortality of 203 relatives of the 14 RTB patients with second tumors was examined, and no excess was observed (11/11). To determine whether the excess might be attributable to an unexpressed RTB gene or precursor, the mortality experience was examined in 6 kindreds in which parents, unaffected by RTB, had more than 1 child with RTB. Among these 72 relatives a significant excess in cancer deaths was observed (8/2). The findings demonstrate a modest overall cancer excess in relatives of hereditary RTB patients and suggest it may be attributable to an unexpressed RTB gene or precursor in a small number of kindreds. Mechanisms for an apparent "precursor" might involve a delayed mutation, genetic mosaicism, or a submicroscopic balanced chromosomal translocation.

Adolescent↗
PubMed1983

Reduced NOR association frequency in a 13/18 translocation chromosome. A family study.

The association frequency of a functional, intercalary NOR in fibroblasts of five carriers of a translocation t(13;18) was significantly lower than the average association frequency of normal G- and D-group chromosomes in the same carriers. This decreased coefficient of association does not seem to be attributable to partial loss of the NOR during rearrangement or to a loss of NOR activity, as indicated by silver staining. It is hypothesized that either (1) interphase associations including this chromosome form less frequently or, more likely, (2) associations with this chromosome are differentially susceptible to physical disruption due to flattening of association complexes during cell preparation. The presence of this abnormal NOR chromosome did not affect the association behavior of normal G- and D-group chromosomes in carrier cells. In addition, the present study supports previous observations that G-group chromosomes associate with a greater average frequency than D-group chromosomes.

Chromosome Mapping↗
PubMed1982

Familial renal cell carcinoma with a 3;11 chromosome translocation limited to tumor cells.

Cytogenic studies were performed on the direct chromosome preparations of the renal cell carcinoma cells and the cultured peripheral blood lymphocytes of a patient with familial renal cell carcinoma. The results revealed a specific, acquired translocations (3p;11p) present in the majority of metaphases of the tumor, indicating that the development of renal cell carcinoma is associated with a deletion in the proximal end of 3p. Renal cell carcinoma is thus the third example--the first two being retinoblastoma and Wilms' tumor--of a chromosomal deletion occurring germinally or somatically in association with a specific tumor. This finding adds further support to the existence of specific human cancer genes.

Adenocarcinoma↗
PubMed1982

Wilms tumor with aniridia/iris dysplasia and apparently normal chromosomes.

Two patients with Wilms tumor, iris dysplasia (complete aniridia in one and subtle iris defects in the other), normal karyotypes, and no gene loss demonstrable by enzyme marker and direct DNA analyses are presented. The findings indicate that aniridia and less severe iris defects define a risk for Wilms tumor even in the absence of del (11p13), and that there is as yet no consistent biochemical genetic marker for the aniridia-Wilms tumor association.

Adolescent↗
PubMed1982

Carotid body tumors in humans: genetics and epidemiology.

Genetic factors in the etiology of carotid body tumors (CBT) were sought in a medical record review of 222 histologically diagnosed cases at 12 U.S. medical centers. Patients in the series, which had a marked female predominance (146 females:76 males), usually developed tumors between the fourth and seventh decades of life (mean, 44.7 yr). In 16 patients who also had other extra-adrenal paragangliomas, suggesting a multiple primary tumor syndrome, CBT were diagnosed significantly earlier (mean, 35.4 yr; P less than 0.01). The occurrence of thyroid cancer in 5 other patients appeared to be excessive. Familial CBT was recognized in 16 patients from 13 affected families, including 9 newly ascertained kindreds. Compared with non-familial lesions, familial CBT tended to develop bilaterally (38% vs. 8% unilaterally) and at slightly earlier ages (41.6 vs. 44.9 yr). CBT was reported to occur in an autosomal dominant pattern in some families and within sibships in others; relatives were not examined for confirmation. The familial findings are generally consistent with a two-step mutation model of the development of hereditary and nonhereditary CBT; apparent deviations from the model might be clarified with additional data on this rare neoplasm.

Adolescent↗
PubMed1981

Familial retinoblastoma and chromosome 13 deletion transmitted via an insertional translocation.

Surviving persons from a kindred in which retinoblastoma occurred over four generations, transmitted by eight unaffected individuals, underwent chromosomal analysis. The results revealed that the development of retinoblastoma was associated with a constitutional chromosome deletion del(13)(q13.1q14.5) and that the unaffected transmitting state was associated with a balanced insertional translocation. These findings indicate that predisposition to retinoblastoma may be attributed to the loss of specific genetic material and that a chromosomal mechanism may explain apparent lack of gene penetrance in certain families. The development of unilateral, and not bilateral, retinoblastoma suggests either that the chromosome deletion is different from the mutation of heritable retinoblastoma in general, or that the chromosome deletion lessens the probability of subsequent somatic carcinogenic events.

Carboxylesterase↗
PubMed1980

Bone sarcoma as a second malignant neoplasm in children: influence of radiation and genetic predisposition for the Late Effects Study Group.

Osteosarcoma or chondrosarcoma developed as a second malignant neoplasm (SMN) in 40 of 188 individuals with SMN whose first neoplasm occurred in childhood. A genetic susceptibility to cancer was found in 23; the SMN developed in an irradiated field in 32; both factors wer present in 16; neither in one. When a genetic predisposition was present, radiation shortened the interval to SMN. The intervals between tumors and the age at which the bone sarcomas developed in relation to genetic disease and therapy were analyzed by a two-mutation hypothesis. Studies of SMN in childhood permit us to make observation about the role of genetic factors and environmental mutagens in cancer etiology.

Adolescent↗
PubMed1980

The nature of cancer and the mechanisms of its control: a review.

Observations on the nature of spontaneous tumours of mammary gland origin in mice, published over a 60-year period in 320 papers, are reviewed. Data presented are (1) development of adequate experimental mice; (2) comparative studies on transplantable, chemically induced and spontaneous tumours by diverse genetic procedures, and (3) tumour regressions obtained with nucleosides. The fundamental conclusion derived from these data is that a genetic change, comparable to a somatic mutation, is involved in the origin of cancer. Nucleosides, especially 5-methyl cytidine (a mild mutagen), have been indicated in the controlling mechanism for this genetic change. The nucleosides appear to be involved in the stabilization of the helical formation of the chromatid strand. The concept of induced stability of chromosome behaviour is discussed, and a number of other aspects including viral and endocrine influence, and histocompatibility.

Animals↗
PubMed1979

Risk of radiation-related subsequent malignant tumors in survivors of Ewing's sarcoma.

Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 years, 4 new bone tumors were observed, whereas 1.2 x 10(-3) were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors.

Adolescent↗
PubMed1978

Three mice, two blind.

In a closed colony of approximately one million mice which had been rigidly pedigreed (brother to sister) from a few original mice, three unusual mice have appeared. These three have obviously deviated from what would be expected according to the accepted laws of inbreeding geneity. Thus three unexpected incidences of increased variability have occurred three times in addition to the occasional appearance of new mutations (approximately one in 26,000 mice). The first mouse developed a sudden increase in susceptibility to spontaneous tumors of mammary origin. She became the mother of the well-known C family used extensively in cancer research. The second mouse clearly exhibited, among clear-cut altered biological characteristics, several somatic mutations, thus indicating an unstable genetic condition. The third mouse developed a highly significant capacity to regress and eliminate spontaneous tumor tissue. The conclusion is reached that unstable biological states arise occasionally during the process of inbreeding.

Animals↗