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Biomedical subjects

W D Thompson

Publications and source records attributed to W D Thompson.

At least 19 recordsLinked to original sources
PubMed1996

The genetic attributable risk of breast and ovarian cancer.

BACKGROUND: The age-specific proportion of breast and ovarian cancer in the general population that is likely to be due to a breast/ovarian cancer susceptibility gene(s) is estimated. In addition, the age-specific penetrance of ovarian cancer for women predicted to be carriers of a susceptibility gene is calculated using population-based data. METHODS: Data are from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, which includes 4730 breast cancer cases aged 20 to 54 years. Information regarding the occurrence of breast and ovarian cancer was collected for mothers and sisters of the cases during an in-home interview. The probability of being a breast cancer susceptibility gene carrier was calculated for each of the breast cancer cases using information on the family history of breast cancer. The calculated risk of ovarian cancer in the first-degree relatives of breast cancer cases with a high probability of being a gene carrier is compared with that seen in first-degree relatives of breast cancer cases with a low probability of being a gene carrier and used to calculate the proportion of ovarian cancer cases that are likely to be due to a breast/ovarian susceptibility gene(s) as well as the age-specific risk of developing ovarian cancer for gene carriers. RESULTS: Approximately 10% of ovarian cancer cases and 7% of breast cancer cases in the general population are estimated to be carriers of a breast/ovarian cancer susceptibility gene; these women are found primarily in families characterized by multiple cases of the early onset of breast cancer. The proportion of breast cancer cases predicted to be attributable to the gene decreases markedly with age; approximately 33% of cases age 20-29 years compared with approximately 2% of cases age 70-79 years. The proportion of ovarian cancer cases predicted to be due to the susceptibility gene ranges from 14% among patients diagnosed in their 30s to 7% among those diagnosed in their 50s. Carriers are predicted to have at least 15 times the age-specific risk of ovarian cancer of noncarriers. Among women predicted to carry the gene, the cumulative risk of developing ovarian cancer by the age of 59 years is approximately 10%. CONCLUSIONS: The estimates provided may prove helpful to clinicians until such time as large-scale population-based screening for breast and ovarian cancer susceptibility genes is possible.

Adult↗
PubMed1996

Tubal sterilization and the risk of endometrial cancer.

Several animal and human studies suggest that tubal occlusion may curtail ovarian function, altering the production and balance of endogenous estrogens and progesterone, 2 hormones closely related to endometrial carcinogenesis. Despite this, and the increasing world-wide popularity of this method of contraception, little is known about its relationship with the risk of developing endometrial cancer. To assess whether tubal sterilization influences a woman's risk of developing epithelial endometrial carcinoma, data from a large multicenter population-based case-control study of endometrial cancer were analyzed. Cases were 437 women aged 20 to 54 years with histologically confirmed epithelial endometrial cancer ascertained through 6 population-based cancer registries in the United States. Controls were 3200 women selected at random from the populations of the areas from which the cases were detected. As compared with women who had never had tubal sterilization, women who had had this surgery had a crude odds ratio of 0.58 [95% confidence interval (CI), 0.43-0.78]. However, after adjusting for the combined confounding effects of age and parity, the magnitude of the protective association decreased to 0.87 (95% CI, 0.63-1.20). The magnitude of the protective effect did not significantly change with years since surgery or age at surgery. Although a modest, non-significant protective effect is suggested, these findings indicate that tubal sterilization does not substantially alter the risk of developing epithelial endometrial cancer in women 20 to 54 years of age. If there is an increase in risk, these data indicate that it is unlikely to be any greater than 20%.

Adult↗
PubMed1996

Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.

BACKGROUND: We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.

Adolescent↗
PubMed1996

A population-based study of endometrial cancer and familial risk in younger women. Cancer and Steroid Hormone Study Group.

Endometrial cancer remains an important cause of morbidity and mortality in the United States, and recent genetic evidence supports the hypothesis that hormonal dysregulation is not the only important risk factor for this tumor. This multicenter, population-based case-control study investigated familial aggregation of endometrial cancer and other cancers. Cases were 455 women 20-54 years of age diagnosed with histologically confirmed primary epithelial carcinoma of the endometrium. Controls consisted of 3216 women 20-54 years of age identified by random-digit dialing. Family histories of cancer in female relatives were obtained by interview of cases and controls. Endometrial cancer in a first-degree female relative increased the risk of endometrial cancer by nearly 3-fold [odds ratio (OR), 2.8; 95% confidence interval (CI), 1.9-4.2]. Cases also reported significantly more colorectal cancer in family members than did controls (OR, 1.9; 95% CI, 1.1-3.3). Family history of cancer of the cervix, lung, ovary, and thyroid was not significantly associated with endometrial cancer, and breast cancer was not related unless more than one relative was affected. Family history of endometrial cancer is an independent risk factor for cancer of the endometrium. In addition, the observed association with a family history of colorectal cancer suggests that genes important in familial colorectal cancer may have substantial implications for endometrial cancer. Nearly 5% of incident endometrial cancer among women between the ages of 20 and 54 may be attributable to a family history of endometrial cancer, and 2% may be related to colorectal cancer.

Adult↗
PubMed1995

An evaluation of the staining of lymphomas and normal tissues by the rabbit polyclonal antibody to protein gene product 9.5 following non-enzymatic retrieval of antigen.

We have previously described the staining of normal follicle centre lymphoid cells by the rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5), following an antigen unmasking step employing heat pretreatment. Applying this finding to a range of lymphomas to determine whether this phenomenon could have a role in identifying lymphomas of follicle centre origin revealed no relationship between type or grade of lymphoma and staining of neoplastic cells. Testing a range of normal tissues following antigen retrieval displayed increased sensitivity and a greater range of tissue positivity. Immunoblots of gel electrophoresed tonsil and brain extract were performed. Although subjecting these blots to antigen unmasking increased sensitivity, no novel epitopes, in terms of additional bands, appeared. This suggested that antibody specificity remained unaltered.

Blotting, Western↗
PubMed1995

Early adult body weight, body mass index, and premenopausal bilateral breast cancer: data from a case-control study.

Previous studies using current or recent adult body weight and body mass index are inconclusive as to a possible effect of increased body mass on premenopausal breast cancer incidence. Only five studies have presented data on early adult body mass, and no study has reported these data for premenopausal bilateral breast cancer. Because premenopausal bilateral breast cancer is assumed to be partly genetic and partly environmental in origin, it is crucial to identify possible modifiable risk factors for this cancer. We present data on early adult body weight and body mass (Quetelet Index, QI) from a case-control study of 142 premenopausal bilateral breast cancer cases from Los Angeles County, California, Connecticut, and Quebec, Canada, and 229 sister controls. The odds ratio (and 95% confidence interval) of premenopausal breast cancer adjusted for age, education, alcohol consumption, and oral contraceptive use was 0.7 (0.3-1.4) for women in the highest tertile of QI at age 18. The results do not suggest that elevated body mass index at a young age increases the risk of premenopausal bilateral breast cancer, but lend only weak support to the hypothesis of an inverse association between body mass index and premenopausal breast cancer.

Adolescent↗
PubMed1995

p53 mutation and expression in lymphoma.

Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.

Adult↗
PubMed1995

Reduced breast cancer risk after remarriage: evidence of genetic-immune protection.

Several reproductive factors have been found to be associated with breast cancer. Based on an immunologic rather than strictly hormonal interpretation of these observations, we hypothesized that, beyond the observed associations relating to pregnancy per se, multiple marriages would be found to protect women against breast cancer. We obtained cases and controls from linked records from the Utah Cancer Registry and genealogic records. A total of 2,414 women with newly diagnosed breast cancer and 9,138 individually matched controls were included. The unadjusted odds ratio for each marriage after the first was 0.81 [95% confidence interval (CI) = 0.68-0.97]. After adjustment for major reproductive factors, multiple marriages were still found to reduce the risk of breast cancer (odds ratio = 0.86; 95% CI = 0.72-1.03). The findings are consistent with the operation of an immunologic mechanism in the etiology of breast cancer and suggest that the gene/antigen responsible for this effect is quite common in males. Further empirical evaluation of the fetal antigen hypothesis seems warranted.

Aged↗
PubMed1994

Maternal pattern of reproduction and risk of breast cancer in daughters: results from the Utah Population Database.

BACKGROUND: Several studies have found that daughters born to older mothers have an elevated risk of breast cancer, and an endocrine hypothesis, among others, has been developed to explain these findings. Three recent studies have failed to find a consistent maternal age effect, indicating a need for further exploration of this issue. PURPOSE: We used Utah breast cancer records linked to genealogical records to investigate maternal and paternal age and other maternal reproductive factors in relationship to the daughter's risk of breast cancer. METHODS: The study group consisted of 2414 breast cancer case patients and 9138 individually matched control subjects. Breast cancer diagnoses were ascertained through the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The case patients and control subjects were born between 1875 and the end of 1947, and the mean age at diagnosis of the case patients was 65.9 years. RESULTS: No consistent effect for maternal or paternal age was found, except possibly among women who were firstborn children (odds ratio [OR] = 1.42 for a 10-year differential in maternal age; 95% confidence interval [CI] = 1.00-2.00). Further examination of the data indicated that mothers of case patients experienced long intervals between marriage and their first birth but not between subsequent births, and they went on to have fewer children. For each year of delay between the mother's marriage and first birth, the odds of breast cancer in the daughter increased 1.05-fold (95% CI = 1.01-1.10). CONCLUSIONS: We found no evidence of a consistent maternal age effect with regard to breast cancer risk in the daughter, but we did find evidence that the mothers of women who go on to get breast cancer have a reproductive pattern that could suggest some form of underlying infertility. IMPLICATIONS: These findings widen the epidemiologic support for the fetal antigen hypothesis, which is an immunogenetic explanation for the relationships between reproductive factors and breast cancer risk. That hypothesis provides strategies for the identification of breast cancer genes and the eventual development of a breast cancer vaccine.

Aged↗
PubMed1994

Genetic epidemiology of breast cancer.

It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk of developing the disease. Recent segregation analyses of population-based data on familial patterns provide evidence for a rare autosomal dominant allele that increases a carrier's susceptibility to breast cancer. The estimated proportion of breast cancer patients who carry this allele declines sharply with age at diagnosis. Empirical estimates of the risk associated with particular patterns of family history of breast cancer indicate the following: (1) having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5-3-fold, depending on age, (2) having multiple first degree relatives affected is associated with particularly elevated risks, (3) having a second-degree relative affected increases the risk by approximately 50%, (4) affected family members on the maternal side and the paternal side contribute similarly to the risk, (5) a family history of breast cancer is associated with bilateral disease, and (6) breast cancer in males is associated with breast cancer in female relatives in much the same way as is breast cancer in women. Ovarian cancer clearly has been shown to be associated with breast cancer in families, and genetic linkage has provided strong evidence for a breast-ovarian cancer gene located somewhere on chromosome 17q. At the population level, having a first degree relative with ovarian cancer may be at least as predictive of a woman's risk for developing breast cancer as is having a second-degree relative with breast cancer. Considerably weaker evidence points to a possible familial relationship between breast and endometrial cancer and between breast cancer in women and prostatic cancer in males. The clinical applications of the genetic epidemiology of breast cancer are complicated by uncertainty as to the efficacy of mammographic screening in women under the age of 50. For the vast majority of women with a positive family history, the epidemiologic evidence does provide the basis for offering considerable reassurance in that risks are not extremely high. For that rather small subgroup at exceptionally high risk, realistic estimates of the magnitude of absolute risk over the next 10-20 years may be more informative and less alarming than lifetime probabilities.

Age Factors↗
PubMed1994

Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction.

BACKGROUND: Improvements in screening techniques have made significant contributions to the early detection of breast cancer. Physicians thus face the task of providing appropriate screening schedules for their patients. One group for whom this is particularly important are those women with a family history of breast cancer. METHODS: In this report, data from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, are used to provide age-specific risk estimates of breast cancer for women with a family history of breast cancer. The data set includes 4730 patients with histologically confirmed breast cancer age 20-54 years and 4688 control subjects who were frequency matched to patients by geographic region and 5-year age intervals. The data set also includes family histories of breast cancer in mothers and sisters of both patients and control subjects. RESULTS: Genetic models fit previously to these data by the authors have provided evidence for a rare autosomal dominant allele that results in increased susceptibility to breast cancer. In addition, these models predict that women who carry the allele are at greater risk of developing breast cancer at any age than are women who do not carry the allele. The increase in risk in carriers versus noncarriers does, however, decrease with increasing age. Based on the parameters of this model, age-specific risks for a woman with one or more relatives affected with breast cancer at various ages at onset are given. CONCLUSIONS: These tables can be used for the purpose of counseling women at high risk of breast cancer development, that is, women with a family history of breast cancer.

Adult↗
PubMed1994

Management of non-palpable breast lesions detected mammographically.

A total of 212 consecutive fine-wire localization breast biopsies in 202 patients were performed on impalpable mammographically suspicious lesions. Preoperative fine-needle aspiration cytology was performed on 159 lesions and was valuable in planning the extent of the fine-wire localization biopsy. All 212 target lesions were accurately biopsied during the initial surgery. Overall, 134 lesions were malignant and 78 benign (benign:malignant ratio 1:1.72), with fewer biopsies for benign lesions performed in screened patients (benign:malignant ratio 1:2.43) than in those with symptoms (ratio 1:1). Breast conservation was achieved in 72 patients (80 per cent) with screen-detected in situ or invasive carcinoma and in 19 of 37 presenting via a symptomatic clinic. In 160 of 202 patients (79 per cent) the initial fine-wire localization biopsy was diagnostic and therapeutic.

Biopsy, Needle↗
PubMed1994

Non-enzymatic retrieval of antigen permits staining of follicle centre cells by the rabbit polyclonal antibody to protein gene product 9.5.

The rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5) will detect the L1 isoenzyme of ubiquitin carboxy-terminal hydrolase (UCH), which is a marker for neurones and neuroendocrine tissue. We re-evaluated this antibody using the technique of non-enzymatic antigen retrieval (boiling sections in citrate buffer, heated by microwave oven) followed by streptavidin-biotin-peroxidase staining. Due to the fortuitous choice of appendix as positive control material containing small nerves, we found strong, repeatable cytoplasmic and nuclear staining of lymphoid follicle centre cells in addition to neural tissue. This effect could be repeated on other lymphoid tissues and was not dependent on microwave heating, but did require boiling in an ionic buffer solution. Staining was also observed with a fresh batch of antibody and with four of the five different batches of antibody which were supplied to us. This pattern was not obtained in fresh tissue, in fixed material following trypsinization, or by increasing the primary antibody concentration. We suggest that the boiling of sections in citrate buffer is exposing an epitope for the anti-PGP9.5 antibody which is inaccessible in the native or fixed state and therefore we would recommend retesting of antibody specificity following non-enzymatic retrieval of antigen.

Animals↗