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Biomedical subjects

W D Thompson

Publications and source records attributed to W D Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1993

A linkage analysis of D17S74 (CMM86) in thirty-five families with premenopausal bilateral breast cancer.

We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.

Age Factors↗
PubMed1993

Relationship between breast histopathology and family history of breast cancer.

BACKGROUND: The relationship between breast cancer histology and a number of epidemiologic risk factors associated with breast cancer was examined in 4071 histologically confirmed breast cancer cases aged 20 to 54 years from the Cancer and Steroid Hormone Study. METHODS: The distribution of risk factors, which included a family history of breast cancer, age at onset of breast cancer, laterality, race, age at menarche, age at menopause, history of benign breast disease, parity, number of livebirths and number of stillbirths, and age at first childbirth, were examined by histologic subgroup. To determine whether histology is associated with familial risk of breast cancer, a Cox proportional hazards model was used, modeling time to onset of breast cancer among mothers and sisters. RESULTS: Cases with medullary carcinoma were found to be significantly younger than cases with other tumor types in these data. In addition, medullary carcinoma was reported more frequently among black cases than among white cases. Cases with lobular carcinoma in situ were significantly more likely to have a mother and/or sister affected with breast cancer than cases with other tumor types and were also more likely to be bilateral, although few of these cases were both bilateral and reported a family history of breast cancer. The highest reported rates of benign breast disease occurred in cases with carcinoma in situ (both ductal and lobular) and tubular carcinoma. The remaining risk factors showed no association with histology. CONCLUSIONS: The current study clarifies the extent and nature of the relationship between breast cancer histology and epidemiologic risk factors including a family history of breast cancer.

Adult↗
PubMed1993

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men.

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Paget's disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.

Age Factors↗
PubMed1993

The calculation of breast cancer risk for women with a first degree family history of ovarian cancer.

Recent linkage analyses demonstrate the strength of the genetic association between breast and ovarian cancer in some families. These findings highlight the importance of considering a woman's family history of ovarian cancer in the calculation of her risk of breast cancer. In this study, data on breast and ovarian cancer from the Cancer and Steroid Hormone Study, a large, population-based, case-control study conducted by the Centers for Disease Control, are used to calculate age-specific and cumulative risks of developing breast cancer for a woman with a first degree family history of ovarian cancer. These risks are calculated using maximum likelihood estimates from an autosomal dominant genetic model fit previously to the observed age-specific recurrence data of breast cancer among first degree relatives of the breast cancer cases and controls in these data as well as from genotype-specific estimates of lifetime ovarian cancer risk derived from this model. Under this model, the lifetime risk of developing breast cancer for a woman with one or two first degree relatives affected with ovarian cancer is estimated to be approximately 13% and 31%, respectively. A woman with one first degree relative affected with ovarian cancer and one first degree relative affected with breast cancer has an estimated risk of 40 percent of developing breast cancer by age 79 years if the relative with breast cancer was diagnosed in her thirties. This risk decreases with increasing age of onset of the relative affected with breast cancer.

Adult↗
PubMed1993

Presence of growth-stimulating fibrin degradation products containing fragment E in human atherosclerotic plaques.

The key event in the formation of stenosing atherosclerotic lesions is widely thought to be smooth muscle cell proliferation, but the factors primarily responsible for initiating this remain uncertain. Previously we have shown that aqueous extracts of proliferative types of human atherosclerotic plaque stimulate cell proliferation in the chick chorioallantoic membrane (CAM). This has been attributed largely to the fibrin degradation products in the extracts, components removeable by affinity chromatography. We now demonstrate that the fibrinogen content of the extract, removeable by clotting out with thrombin, also makes a contribution to the activity by forming fibrin on the surface of the CAM. Affinity chromatography experiments using anti fragment D and E antisera indicate that activity resides in the E-containing fibrin fragments, consistent with previous work with FDP prepared in vitro.

Allantois↗
PubMed1993

Inhibition of wound healing in mice by local interferon alpha/beta injection.

Tumour vascular endothelium has been observed previously to be damaged by local injection of interferon alpha/beta, apparently before the onset of necrosis and regression of experimental tumours. In order to distinguish the effect of interferon alpha/beta on the vasculature from direct effects on tumour, the angiogenesis of wound healing was chosen for study. Injection of interferon alpha/beta subcutaneously adjacent to each wound at days 0 to 4 resulted in a markedly reduced rate of healing with poor edge reunion by day 3. Histologically, there was delay in the initiation of proliferation of not only capillary buds, but also fibroblasts and, to a lesser extent, epithelium across the incision. Nevertheless, no endothelial injury was seen at light or electron microscopic level. Healing subsequently resumed the normal pattern, though delayed, day 9 wounds resembling normal day 5 wounds. We conclude that interferon alpha/beta inhibits wound healing in mice by inhibition of proliferation of many cell types in addition to endothelium.

Animals↗
PubMed1993

Leukemia, lymphoma, and multiple myeloma after pelvic radiotherapy for benign disease.

The relationship between exposure to sparsely ionizing radiation and mortality due to cancers of hematopoietic and lymphopoietic tissues was studied among 12,955 women treated for benign gynecological disorders at any of 17 hospitals in New England or New York State and followed for an average of 25 years; 9770 women were treated by radiation (intracavitary 226Ra, external-beam X rays), while 3185 were treated by other methods, including curettage, surgery, and hormones. The average age at treatment was 46.5 years, and the mean dose to active bone marrow among irradiated women was 119 cGy. Forty deaths due to acute, myelocytic, or monocytic leukemia were observed among irradiated women. This number was 70% higher than expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.7; 90% confidence interval (CI) 1.3-2.3]. A deficit was recorded among nonirradiated women, based on three observed deaths (SMR = 0.5; 90% CI 0.1-1.2). A well-defined gradient in the SMR with dose among exposed women was not detected. The SMR was highest within 5 years after irradiation but remained elevated even after 30 years. The temporal pattern differed by subtype of leukemia: excess mortality due to chronic myelocytic leukemia occurred almost exclusively within the first 15 years, whereas the SMR for acute leukemia, though also elevated, varied little over time. Cancers of lymphoreticular tissue occurred more often than expected based on U.S. mortality rates, but not appreciably differently for irradiated and nonirradiated women. There was little or no evidence of effects attributable to radiotherapy for chronic lymphocytic leukemia [relative risk (RR) = 1.1; 90% CI 0.5-3.0], Hodgkin's disease (RR = 0.9; 90% CI 0.3-3.2), non-Hodgkin's lymphoma (RR = 0.9; 90% CI 0.6-1.6), or multiple myeloma (RR = 0.6; 90% CI 0.3-1.4). These results corroborate previous findings indicating that acute and myelocytic leukemias are the most prominent malignancies after exposure to sparsely ionizing radiation, occurring in excess shortly after irradiation, and that lymphomas are either not caused by radiation or are induced only rarely.

Bone Marrow↗
PubMed1993

Fibrin degradation products in growth stimulatory extracts of pathological lesions.

We have previously shown that similar patterns of fibrin degradation products (FbDP) by gel electrophoresis and immunoblotting are present in extracts of human atherosclerotic plaques, human and experimental wounds and breast cancers. Such extracts were also shown to stimulate cell proliferation including angiogenesis in the chick chorioallantoic membrane, now shown also for breast cancers. Removal of FbDP from plaque extracts by an anti-fibrinogen affinity column, or by an anti-fragment E column, reduced activity. Human FbDP prepared in vitro were active, but not FgDP. Fibrin fragment E was active, and we also showed that admixture of FbDP with a polyclonal rabbit anti-fibrin E but not anti-fibrin D neutralized activity. However attempts to raise comparable monoclonal blocking antibodies were hindered by species similarities. The response of the Balb/c mouse was predominantly directed at minor D contaminants, in contrast to the Sprague-Dawley rat which responded to fibrin fragment E in our antigen preparation.

Animals↗
PubMed1992

Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer.

This study examined risk factors for development of a contralateral breast cancer among 4,660 US women diagnosed with a first primary breast cancer between 1980 and 1982. The authors believe it to be the first prospective cohort study on this topic that has employed direct patient interviews. All subjects were interviewed within 6 months of the diagnosis of their initial tumor as part of the multi-center, population-based, case-control Cancer and Steroid Hormone Study, and they were followed until the end of 1986 through the Surveillance, Epidemiology, and End Results program. Exclusive of those diagnosed during the initial 6 months after diagnosis of a first primary, 136 second primary breast cancers were identified. Proportional hazards models were used to assess the independent effects of multiple predictors. Specific risk factors evaluated included: age at diagnosis of first primary, exposure to exogenous hormones, menstrual and reproductive histories, tumor characteristics, demographic variables, and treatment modalities. The age-specific incidence rates of second primary breast cancer were higher in all age categories than are the incidence rates of breast cancer in the general population, yet the age at diagnosis of first primary breast cancer was not an important predictor of contralateral breast cancer. The risk of contralateral breast cancer was increased among cohort members who reported a personal history of benign breast biopsy (multivariable-adjusted rate ratio (RR) = 1.69, 95% confidence interval (CI) 1.13-2.53) and in those with an initial tumor that was classified as lobular carcinoma (multivariable-adjusted RR = 1.96, 95% CI 1.17-3.27). Treatment with chemotherapy for the first primary was associated with a lower risk of development of a second breast cancer (multivariable-adjusted RR = 0.56, 95% CI 0.33-0.96), while radiation therapy had little effect on the risk (multivariable-adjusted RR = 1.19, 95% CI 0.78-1.80).

Adult↗
PubMed1992

The genetic epidemiology of second primary breast cancer.

It is well established that women with a family history of breast cancer run a higher risk of breast cancer than do women without a family history. The evidence, however, is less clear regarding a possible association between a family history of breast cancer and risk of second primaries. The purpose of this prospective study was to estimate the risk for second primary breast cancer associated with having a family history of breast, endometrial, and ovarian cancers. A cohort of 4,660 women with a first primary breast cancer diagnosed between 1980 and 1982 were interviewed as part of the Cancer and Steroid Hormone Study, a multi-center population-based case-control study, and followed through eight Surveillance, Epidemiology, and End Results (SEER) program registries for 4 to 6 years. Of these women, 136 developed a second primary breast cancer in the contralateral breast at least 6 months after diagnosis of the first primary. Cox proportional hazards modeling techniques were used to model the time to onset of second primary breast cancer while adjusting for multiple predictors. The risk of contralateral breast cancer was elevated among cohort members who reported a history of breast cancer in a first-degree relative (multivariable-adjusted rate ratio (RR) = 1.91, 95% confidence interval (CI) = 1.22-2.99). Early age at onset (< 46 years) in the relative further increased the risk of developing contralateral breast cancer (sister: multivariable-adjusted RR = 3.36, 95% CI 1.62-6.98; mother: multivariable-adjusted RR = 2.35, 95% CI 1.02-5.43). Bilateral breast cancer in mothers was also associated with more than a two and a half-fold increase in risk (multivariable-adjusted RR = 2.55, 95% CI 1.02-6.35). The association between family history of breast cancer and risk of contralateral breast cancer did not vary substantially according to age at onset of the first primary breast cancer. The age-adjusted rate ratio for development of a second primary breast cancer among women with a first-degree relative with endometrial cancer was 2.13 (95% CI 1.04-4.35), while the corresponding rate ratio among women with a family history of ovarian cancer was 1.69 (95% CI 0.42-6.83). There was little evidence that age at onset among the relatives with endometrial or ovarian cancer affected the risk. Some of these findings have not been previously reported and need replication in future studies.

Adult↗
PubMed1992

Breast cancer in men: risk factors with hormonal implications.

Cases included in a population-based case-control study of breast cancer in men were recruited from 10 geographic areas of the United States from 1983 to 1986. Controls, matched to cases on age and geographic area, were selected by random digit dialing for men under age 65 years and from Health Care Financing Administration files for older men. Results are based on responses from 227 cases and 300 controls to questions asked in a standardized personal interview. An increased risk of breast cancer was most strongly associated with undescended testes and was also related to orchiectomy, orchitis, testicular injury, late puberty, and infertility; and a decreasing trend in risk was observed with an increasing number of children. Relative risk estimates were also elevated in relation to a history of high blood cholesterol, rapid weight gain, benign breast conditions, and possibly obesity. These findings suggest that breast cancer in men develops in response to androgen deficiency associated with testicular dysfunction and under conditions associated with excess estrogen. Risk was also found to be elevated in men with a history of amphetamine use, diabetes, and cigar smoking and reduced in men with prior head trauma.

Adult↗
PubMed1992

Angiogenic activity of fibrin degradation products is located in fibrin fragment E.

The source of angiogenic activity of fibrin degradation products has been sought in a series of experiments, applying degradation products from different types of fibrin and fibrinogen to the chick chorioallantoic membrane. The presence of platelets or fibronectin during clotting was not essential for activity, and neither was crosslinking. Fibrinogen degradation products were non-stimulatory, as was serum. Molecular sieve column chromatography indicated a range of active fragments. Admixture of active fibrin degradation products with antifibrin fragment E, but not D, antiserum neutralized activity. Preparations containing only fibrin fragment E retained activity. A commercial preparation of fibrinogen fragment E was inactive until treated with thrombin. These experiments point to fibrin fragment E being the source of angiogenic activity, with thrombin cleavage being the essential step in generating activity.

Animals↗
PubMed1992

Fibrinogen/fibrin in atherogenesis.

Fibrin is a major component of many atherosclerotic plaques. Within the intima there is continuous formation of fibrin, and continuous fibrinolysis. In aortic lesions, a lipoprotein bound to fibrin can be released by incubation with plasmin. Most of this lipoprotein is accounted for by Lp(a). The atherogenicity of Lp(a) may be more associated with lipid deposition than with inhibition of fibrinolysis. Fibrin degradation products may be chemotactic to monocyte-macrophages and stimulate smooth muscle cell proliferation.

Antigens↗
PubMed1992

Oral contraceptives and premenopausal bilateral breast cancer: a case-control study.

We estimated the effect of oral contraceptive (OC) use on premenopausal bilateral breast cancer in a matched case-control study. One hundred forty-four cases were identified from population-based registries of Los Angeles County, California, and of Connecticut and from the major hospitals in Montreal and Quebec City. Matched controls were the unaffected sisters of the cases. When age was included in the model, ever-use of OCs for 1 year or more was associated with an odds ratio 1.7 (95% confidence interval = 1.0-2.9). The odds ratios associated with 1-2, 3-6, and 7 years of use were 1.2 (0.61-2.4), 2.5 (1.2-5.3), and 2.0 (0.93-4.2), respectively. Too few women had used OCs before their first full-term pregnancy or before age 25 for these estimates to be informative. Restricting the analyses to women who had ever given birth yielded an odds ratio for ever-use of OCs of 2.1 (1.0-4.4). The results indicate an increased risk of premenopausal bilateral breast cancer associated with OC use.

Adult↗
PubMed1992

Patterns of angiogenic response to mast cell granule constituents.

Agents derived from mast cell granule constituents, and compound 48/80 which stimulates release of mast cell granules, have been used by us to develop new methods for quantitating angiogenesis in the chick chorioallantoic membrane. Two of these methods provide different insights, demonstrating different patterns of response to dosage and over time, produced by different agents. Counting mesenchymal blood vessels is convenient for obtaining dose-response data. Histamine and compound 48/80 have been shown previously to give a sigmoid dose-response curve resulting in a plateau before the lethal dose. This contrasts with the effect of porcine sodium heparin (Evans Biologicals) which results in a minor increase then a relative decline in vessel number due to a failure of growth. Here, the ability to produce angiogenesis or antiangiogenesis appears to be dose-dependent. Measurement of the changes in DNA synthesis, leading to visible angiogenesis, may be performed once the optimal angiogenic dose is known, and again distinctive patterns of response with different agents have been found. Histamine results in a fall then rise to a peak at 36 hr. We now show that two types of heparin each produce a peak at 12 hr. Compound 48/80 results in a distinctive pattern that looks like a composite of the histamine and especially the heparin effects, and this suggests that both are relevant to induction of angiogenesis by mast cells. The elicitation of this pattern of response also provides a method, additional to electron microscopy, for discovering whether or not an angiogenic substance is likely to operate via mast cell stimulation. Such characteristic patterns offer a new way of classifying angiogenic substances.

Animals↗
PubMed1991

Polycystic ovaries and the risk of breast cancer.

Data from a case-control study that was conducted between 1980 and 1982 were analyzed to investigate the possible association between polycystic ovaries and the risk of breast cancer. The multicenter, population-based study included in-home interviews with 4,730 women with breast cancer and 4,688 control women aged 20-54 years. The age-adjusted odds ratio for breast cancer among women with a self-reported history of physician-diagnosed polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The inverse association was not an artifact of infertility, age at first birth, or surgical menopause. Because women with this syndrome have abnormal levels of certain endogenous hormones, the observation of a low risk of breast cancer in this group may provide new insights into hormonal influences on breast cancer.

Adult↗
PubMed1991

Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history.

To determine whether the occurrence of one or more histologic types of uterine sarcoma is related to events in a woman's reproductive life, a population-based case-control study was conducted. One-hundred sixty-seven women newly diagnosed with uterine sarcoma among residents of 6 geographic regions were compared to 208 women selected at random from the same populations with regard to histories of menstruation, pregnancy and childbearing, and breast feeding, as reported during a telephone interview. Compared to women whose menstrual periods began at age 13, women whose menses began earlier were at increased risk of leiomyosarcoma (OR = 2.0, 95% CI 0.9, 4.3); other histologic types were less strongly associated with early age at menarche. Women with leiomyosarcoma and endometrial stromal sarcoma, but not malignant mixed Müllerian tumors, tended to have ceased menstruating 2-3 years later than controls. None of the histologic types was clearly related to parity or to age at first live birth, but each was inversely related to age at last live birth. Associations were observed between leiomyosarcoma and histories of an induced abortion (OR = 4.2, 95% CI 1.2, 14.2) and of breast feeding after a live birth (OR = 0.5, 95% CI 0.3, 1.0); these relationships were not observed for other morphologic variants. These results suggest possible similarities and differences in menstrual and reproductive risk factors among histologic types of uterine sarcoma, and between these malignancies and the more common breast, endometrial and ovarian carcinomas.

Adult↗