Biomedical subjects

B E Storer

Publications and source records attributed to B E Storer.

At least 37 records · Page 2Linked to original sources

PubMed1996

Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women.

Several epidemiological studies have identified an association between nonsteroidal anti-inflammatory drug (NSAID) use and colorectal cancer risk in women. We examined this association in a population-based case-control study in Wisconsin women. Between 1991 and 1992, 184 women ages 40-74 years with colorectal cancer were identified through the statewide cancer registry and 293 population-based control women were randomly selected via telephone. Regular NSAID use was defined as at least twice weekly for 12 months or longer. After adjusting the data for age, controls were more likely than cases to report regular NSAID use (38 versus 27%). Following adjustment for age, prior sigmoidoscopy use, family history of large bowel cancer, and body mass index, women who regularly used NSAIDs were approximately one-third less likely to be diagnosed with colorectal cancer compared to women who did not use NSAIDs [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.40-1.03]. A statistically significant effect of duration of use was identified, although the ORs did not show a consistent trend. No significant effect of frequency of NSAID use was observed. When the type of NSAID used was examined (aspirin or nonaspirin), subjects who used nonaspirin compounds had a statistically significantly lower risk of colorectal cancer (OR, 0.43; 95% CI, 0.20-0.89), compared to nonusers, whereas aspirin users had only a small, nonsignificant reduction in cancer risk (OR, 0.79; 95% CI, 0.46-1.36). These data add support to the hypothesis that regular NSAID use is associated with lower colorectal cancer risk in women and suggest that the type of NSAID used may be important.

Adult↗

PubMed1996

Cigarette smoking and breast cancer.

A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

Age Factors↗

PubMed1995

Cigarette smoking in relation to risk of large bowel cancer in women.

Smoking habits were ascertained by interview from Wisconsin women aged 30-74 years with newly reported diagnoses of colon (n = 536) and rectal (n = 243) cancer and 2315 randomly selected population controls. After controlling for age, body mass index, alcohol consumption, family history of large bowel cancer, and history of screening sigmoidoscopy, significantly elevated risks were observed for women who had ever smoked, in both the colon (odds ratio, 1.28; 95% confidence interval, 1.03-1.58) and rectum (odds ratio, 1.44; 95% confidence interval, 1.08-1.92). Risk significantly increased with greater number of cigarettes smoked per day, longer duration of smoking, and earlier age at initiation for both the colon and the rectum; however, only duration of smoking was not independently associated with risk. Among former smokers, risk for both colon and rectal cancer remained elevated. These data suggest that women who smoke are at elevated risk of both colon and rectal cancer and that increased risk persists even among former smokers.

Adult↗

PubMed1995

Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.

Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.

Breast Neoplasms↗

PubMed1995

Postmenopausal hormone use and risk of large-bowel cancer.

BACKGROUND: The epidemiology of large-bowel cancer suggests a role for endocrine factors in its development. Although analytic studies have not consistently provided evidence for an association between reproductive history and large-bowel cancer, some relatively small studies have observed a reduced risk among women using postmenopausal hormone replacement therapy (HRT). PURPOSE: This study was planned to evaluate more precisely the relationship between HRT and the risk of colon and rectal cancers. METHODS: Female residents of Wisconsin aged 30-74 years with a diagnosis of colon or rectal cancer within 2 years were identified through a statewide tumor registry. Control subjects were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old and from lists of Medicare beneficiaries if they were 65-74 years old. Information on post-menopausal hormone replacement use, medical history, and family history was obtained in telephone interviews. After premenopausal women were excluded, 694 case subjects and 1622 control subjects remained for analysis. The odds ratios and 95% confidence intervals (CIs) obtained from conditional logistic regression models were used to estimate relative risks (RRs). All RRs were adjusted for age, family history of large-bowel cancer, use of screening sigmoidoscopy, and recent alcohol consumption. RESULTS: Compared with postmenopausal women who never used HRT, recent users had an RR of 0.54 (95% CI = 0.36-0.81) for colon cancer and an RR of 0.91 (95% CI = 0.54-1.55) for rectal cancer. This inverse association was observed among users of both estrogen only and combined estrogen and progestin preparations. Decreasing time since last use was inversely associated with colon cancer risk (P for trend < .001). The effect of HRT appeared to be stronger among women at lower absolute risk of colon cancer, particularly among women with lean body mass. CONCLUSIONS: Use of HRT was associated with a statistically significant reduced risk of colon cancer. In contrast, no statistically significant relationship was observed for rectal cancer. Given the widespread use of postmenopausal hormones and the morbidity and mortality from adenocarcinoma of the bowel in women, these findings may have potentially important public health implications.

Aged↗

PubMed1995

Multiple births and risk of breast cancer.

Data from a large, multicenter, population-based case-control study were analyzed to investigate the relation between multiple birth pregnancies and subsequent breast-cancer risk in the gravidas. Women less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, western Massachusetts, Maine and New Hampshire. Controls aged less than 65 years were selected randomly from lists of licensed drivers, and controls aged between 65 and 74 were selected randomly from lists of Medicare beneficiaries. Information on reproductive history and other factors was obtained by means of telephone interviews. After excluding nulliparous women, 5,880 case subjects and 8,217 controls remained for analysis. Multiple birth pregnancies occurred in 146 cases and 218 controls. Adjusted for the number of full-term pregnancies and other confounders, the odds ratio (OR) for any multiple birth pregnancy was 0.94 (95% confidence interval, 0.75 to 1.17). The null association between multiple birth pregnancies and breast cancer remained if the mother's first pregnancy or last pregnancy resulted in a multiple birth. In addition, no trend in risk emerged for age at first multiple birth or time since last multiple birth. While other investigators have suggested biological mechanisms to explain both protective and detrimental effects of multiple births and subsequent development of breast cancer, this study does not support either assertion.

Adult↗

PubMed1995

Assessing breast self-examination.

BACKGROUND: Women practice breast self-examination (BSE) according to their own schedule and skill. This variation in how BSE is performed has complicated the interpretation of studies of BSE efficacy and utilization. METHODS: We compared two methods commonly used to assess BSE competency, self-report of practice and ability to detect lumps in a model, among 81 women participating in a controlled toxicity trial of tamoxifen. Subjects were postmenopausal, were under 65 years of age, and had a history of breast cancer within the past 10 years but were currently free of disease. Women were asked to describe their usual BSE practice and were assigned a score (0-10) based on the number of recommended techniques and positions mentioned. Subjects were then instructed to examine a silicone breast model embedded with lumps (HealthEdCo) and to report any abnormalities. RESULTS: Overall proficiency was low by both measures. No significant correlation (r = 0.16, P = 0.15) was found between the two measures of proficiency. Higher correlations were observed among older women and among those practicing BSE monthly. CONCLUSIONS: This study suggests that the two techniques are not comparably evaluating BSE proficiency. Further, both of these methods are likely to be poor measures of true BSE practice.

Aged↗

PubMed1995

The association of body size and large bowel cancer risk in Wisconsin (United States) women.

Body size is associated with the risk of many diseases, including diabetes, heart disease, and some cancers. To evaluate the association of body size with large bowel cancer, height and weight measurements were ascertained by telephone interview from 779 Wisconsin (United States) women with newly reported diagnoses of carcinoma of the colon and rectum. Controls (n = 2,315) interviewed for this case-control study were selected randomly from Wisconsin driver's license files and Health Care Financing Administration files. The effects of weight and height were examined using multiple logistic regression to control for potential confounding variables. In this study, weight adjusted for height increased the risk of colon cancer (odds ratio [OR] for 72.57-148.33 kg cf 36.29-58.05 kg = 1.4, 95 percent confidence interval [CI] = 1.0-1.9) but did not increase the risk of rectal cancer. Height did not influence risk for cancer of either the colon or the rectum. Left-colon subsite analysis showed especially strong associations with current weight and with percent change in weight since age 18. These data suggest that a dose-response relationship exists between body size and risk of colon cancer in women; body size did not appear to influence risk of rectal cancer.

Adult↗

PubMed1995

The association of reproductive and menstrual characteristics and colon and rectal cancer risk in Wisconsin women.

Reproductive and menstrual characteristics were ascertained by telephone interview from Wisconsin women with newly reported diagnoses of carcinoma of the colon (n = 536) and rectum (n = 243) and 2315 population control subjects. The relationships of parity, age at first full-term pregnancy, age at menarche, regularity and length of menstrual cycles, age at menopause, and type of menopause to colon and rectal cancer were examined. In our study population, no reproductive or menstrual characteristics were significantly associated with colon cancer, although subsite analyses suggested an increased risk for transverse colon cancer in women reporting irregular menstrual cycles. Only parity was associated with rectal cancer; women who had given birth five or more times were at significantly lower risk compared to those who were nulliparous (odds ratio: 0.60; confidence interval: 0.36, 0.99). The odds ratio per birth also suggested an inverse association. These data give little support to the hypothesis that female reproductive events modify colon and rectal cancer risk.

Adult↗

PubMed1994

Lactation and a reduced risk of premenopausal breast cancer.

BACKGROUND: The evidence of an association of lactation with a reduction in the risk of breast cancer among women has been limited and inconsistent. The effect of lactation appears to be confined to premenopausal women with a history of long lactation, but most studies of this relation have been limited in statistical power. We conducted a multicenter, population-based, case-control study with a sample large enough for us to describe more precisely the association between lactation and the risk of breast cancer. METHODS: Patients less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old, and from lists of Medicare beneficiaries if they were 65 through 74 years old. Information on lactation, reproductive history, and family and medical history was obtained by means of telephone interviews. After the exclusion of nulliparous women, 5878 case subjects and 8216 controls remained for analysis. RESULTS: After adjustment for parity, age at first delivery, and other risk factors for breast cancer, lactation was associated with a slight reduction in the risk of breast cancer among premenopausal women, as compared with the risk among women who were parous but had never lactated (relative risk, 0.78; 95 percent confidence interval, 0.66 to 0.91); the relative risk of breast cancer among postmenopausal women who had lactated, as compared with those who had not, was 1.04 (95 percent confidence interval, 0.95 to 1.14). With an increasing cumulative duration of lactation, there was a decreasing risk of breast cancer among premenopausal women (P for trend < 0.001) but not among postmenopausal, parous women (P for trend = 0.51). A younger age at first lactation was significantly associated with a reduction in the risk of premenopausal breast cancer (P for trend = 0.003). As compared with parous women who did not lactate, the relative risk of breast cancer among women who first lactated at less than 20 years of age and breast-fed their infants for a total of six months was 0.54 (95 percent confidence interval, 0.36 to 0.82). CONCLUSIONS: There is a reduction in the risk of breast cancer among premenopausal women who have lactated. No reduction in the risk of breast cancer occurred among postmenopausal women with a history of lactation.

Age Factors↗

PubMed1994

Human T cells in hu-PBL-SCID mice proliferate in response to Daudi lymphoma and confer anti-tumour immunity.

In vitro culture of human peripheral blood lymphocytes (PBL) with Daudi (Burkitt lymphoma) cells results in selective proliferation of V gamma 9/V delta 2 T cells with high cytotoxicity against Daudi cells. After adoptive transfer into severe combined immunodeficient (SCID) mice, these cells exert specific anti-tumour activity against Daudi lymphoma. To test whether cytotoxic V gamma 9/V delta 2 T cells are induced in SCID mice, human PBL injected intraperitoneally were stimulated with irradiated Daudi cells (PBL/Daudi-SCID). After 7-14 days, PBL/Daudi-SCID had a significantly higher percentage of human gamma delta T cells in their peritoneal cavity, lymph nodes and blood than controls (PBL-SCID). DNA content analysis of T cell subsets from PBL/Daudi-SCID showed a significantly higher percentage of cells in S + G2 + M phases of the cell cycle in the TCR-gamma delta-1+ than in CD3+ cell population. Human cells recovered from PBL/Daudi-SCID showed specific cytotoxicity against Daudi cells. PBL/Daudi-SCID inoculated with a lethal dose of Daudi lymphoma survived significantly longer than controls. This protection was specific for Daudi cells and was not mediated by murine natural killer (NK) cells. Thus human peripheral blood T cells grafted in SCID mice proliferate in response to antigen and confer specific immunity.

Animals↗

PubMed1994

Early adulthood physical activity and colon cancer risk among Wisconsin women.

Frequency of strenuous activity during ages 14-22 was ascertained retrospectively from 536 Wisconsin women with newly reported diagnoses of colon cancer and 2315 controls randomly selected from Wisconsin driver's license and Medicare beneficiary lists. Thirty-five % of cases and 34% of controls reported strenuous activity during this period of early adulthood. After adjusting for age, family history of large bowel cancer, history of screening sigmoidoscopy, and body mass index in logistic regression models, women who reported any strenuous activity were at a similar risk of colon cancer as women who did not report activity [odds ratio (OR), 1.02; 95% confidence interval (CI), 0.82-1.27); no significant decrease in risk was seen with increase in frequency of activity (P for trend = 0.84). Results were similar for the right and left colon subsites. These data suggest that early adulthood physical activity may not confer the same protective effect that has been observed with recent physical activity.

Age Factors↗

PubMed1993

Cancer of the large bowel in women in relation to alcohol consumption: a case-control study in Wisconsin (United States).

Age-specific consumption of beer, wine, and liquor was ascertained by telephone interview from 779 women in Wisconsin (United States) with newly reported diagnosis of carcinoma of the colon and rectum. Population controls (n = 2,315) interviewed for this case-control study were randomly selected from Wisconsin driver's license files and Health Care Financing Administration files. Overall, there was a modest indication that high levels of alcohol consumption (11 or more drinks per week) were associated with increased risk of large bowel cancer (adjusted odds ratio [OR] = 1.47, 95 percent confidence interval [CI] = 1.0-2.22). In site-specific analyses, only rectal cancer demonstrated a significant linear trend (P = 0.01) with increasing consumption. Significant beverage-specific effects were observed for liquor and colon cancer: the adjusted ORs for 1-2, 3-5, and 6+ drinks per week were 1.12, 1.68, 1.51, respectively (P trend = 0.01). Beer was associated significantly with rectal cancer: the adjusted ORs for 1-2, 3-5, 6-10, and 11+ drinks per week were 1.25, 1.25, 1.58, 2.42, respectively (P trend = 0.02). Wine consumption was associated inversely with these cancers. These relationships appeared to be consistent for recent, past, and total lifetime consumption, and were not attributable to differences in dietary habits.

Adult↗

PubMed1993

Pharmacodynamics of biological response in vivo after single and multiple doses of interferon-beta.

Interferons (IFNs) induce gene regulation in vivo that may be used to identify effective doses, schedules, and potential correlates of therapeutic response. To critically examine minimum effective dose, duration of response, and cumulative effects of repetitive doses, a range of subcutaneous doses of IFN beta ser was studied in 32 healthy human volunteers. IFN-induced products of gene regulation assessed were beta 2-microglobulin, neopterin, and tryptophan in serum and 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral blood mononuclear cells. Eight subjects per group received 0.09, 0.9, 9, or 45 MU of IFN beta. Responses were measured at 24, 48, and 72 h after single and multiple doses. The lowest biologically effective dose was 0.9 MU; significant (p < 0.02) increases were observed at 24 h in beta 2-microglobulin and cellular 2-5A synthetase activity. At the two higher doses, 9 and 45 MU, changes were observed at 24 h in all products (p < 0.01). A dose response (p < 0.01) over the range of 0.09-45 MU was observed for all these serum and intracellular gene products. Changes in neopterin, beta 2-microglobulin, and cellular 2-5A synthetase correlated significantly with each other. The response to a single dose of IFN beta was as great in magnitude as the response to multiple doses, suggesting an alternate-day schedule would maintain biological response.

2',5'-Oligoadenylate Synthetase↗

PubMed1993

Small-sample confidence sets for the MTD in a phase I clinical trial.

Properties of procedures for interval estimation of the maximum tolerable dose (MTD) in a Phase I clinical trial are examined, using a two-stage stochastic sampling scheme (Storer, 1989) as a paradigm for development. Although the likelihood function for the data arising from such a scheme is identical to one arising under a conditional binomial sampling assumption, intervals based on the exact distribution of the usual large-sample statistics under this assumption do not offer improvement over unadjusted intervals. However, consideration of the distribution of these statistics based on the true stochastic sampling scheme can lead to the construction of intervals with correct coverage probabilities that do not depend on the true values of the model parameters. Membership in the confidence set can be evaluated by Monte Carlo simulation at a restricted maximum likelihood estimate of the nuisance slope parameter, despite upward bias in its estimation from the up-and-down sampling scheme. The lack of information in the small-sample setting is reflected in a large proportion of confidence intervals that include infinite values for the MTD, especially when the dose-response curve is shallow. Intervals based on a likelihood ratio criterion perform best in this regard.

Algorithms↗

PubMed1992

Screening sigmoidoscopy and colorectal cancer mortality.

BACKGROUND: Sigmoidoscopy may reduce colorectal cancer mortality by identifying both cancers and precursor lesions (including polyps) for treatment; however, evidence regarding the efficacy of this technique as a screening procedure is extremely limited. PURPOSE: In the absence of data from randomized controlled trials, we performed a retrospective case-control study to determine if sigmoidoscopy screening is associated with a reduction in colorectal cancer mortality. METHODS: The medical records of 66 members of the Greater Marshfield Community Health Plan (GMCHP) who died of large-bowel cancer from 1979 to 1988 were reviewed for history of screening for colorectal cancer (case subjects). For comparison, the records of 196 GMCHP members of similar gender, age, and enrollment duration were randomly selected for review (control subjects). RESULTS: History of screening sigmoidoscopy was much less common among case subjects (10%) than among control subjects (30%). Risk for death from colorectal cancer was reduced among individuals having had a single examination by screening sigmoidoscopy (odds ratio = 0.21; 95% confidence interval = 0.08-0.52), compared with the risk for those who never had one. The reduction in risk appeared to be limited to tumors in the rectum and distal colon. Neither fecal occult blood testing nor digital rectal examination was associated with a reduction in colorectal cancer mortality. CONCLUSIONS: These results suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon.

Aged↗

PubMed1992

Antilymphoma activity of human gamma delta T-cells in mice with severe combined immune deficiency.

Human Burkitt lymphoma (Daudi) cells grow as disseminated tumors in mice with severe combined immune deficiency (SCID) after either i.v. or i.p. injection. These cells are lysed in vitro by human V gamma 9/V delta 2 T-cells that recognize the groEL homologue on the Daudi cell surface. We report that both Daudi cell-stimulated peripheral blood mononuclear cells (Daudi-PBMC) containing 41-95% of V gamma 9/V delta 2 T-cells and V gamma 9/V delta 2 T-cell clones prolong the survival of SCID mice given inoculations of a lethal dose of Daudi cells. Groups of 6-8-week-old SCID mice were given inoculations i.v. or i.p. of 10(5) Daudi cells followed (through different injection sites) by: (a) 10(7) Daudi-PBMC; or (b) 10(7) unstimulated PBMC; or (c) 0.9% saline solution. All animals in groups (b) and (c) died of disseminated lymphoma, and their survival was significantly shorter than that of mice in group (a) (P < 0.001 for both i.v. and i.p. routes). Significant antitumor effects were also detected when Daudi-PBMC were injected 4 days before or 4 days after Daudi cells (P < 0.05). In vivo depletion of murine natural killer cells by anti-asialo GM-1 rabbit antiserum did not affect survival, suggesting that these cells did not contribute to lymphoma killing. Daudi-PBMC did not exert in vivo antitumor activity against the control Raji lymphoma. Mice receiving i.p. injections of Daudi cells followed by cytotoxic V gamma 9/V delta 2 T-cell clones also survived significantly longer (P < 0.05 for 3 different clones) than animals given Daudi cells alone or Daudi cells followed by noncytotoxic gamma delta T-cell clones. Our results indicate that this model system can be used for studies of human antilymphoma T-cell responses in vivo.

Animals↗

PubMed1992

Absence of biological effects of orally administered interferon-beta ser.

To assess biological effectiveness of interferon (IFN) administered orally, we measured serum IFN and several proteins and metabolites induced by IFN after oral administration of 2.5 mg or 7.5 mg of recombinant IFN-beta ser to 6 healthy volunteers. These IFN-induced metabolites, beta 2-microglobulin, and neopterin in serum, and 2',5'-oligoadenylate (2-5A) synthetase in peripheral blood mononuclear cells, are more sensitive to the presence of IFN than bioassay of IFN in serum. Up to 48 h after oral IFN was administered, serum IFN, beta 2-microglobulin, neopterin, or 2-5A synthetase were not generally increased compared to pretreatment levels, indicating that oral IFN had no significant biological effects.

Adenine Nucleotides↗