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R E Shore

Publications and source records attributed to R E Shore.

At least 19 recordsLinked to original sources
PubMed1995

A prospective study of endogenous estrogens and breast cancer in postmenopausal women.

BACKGROUND: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. PURPOSE: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. METHODS: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling. RESULTS: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. CONCLUSIONS: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. IMPLICATIONS: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life.

Breast Neoplasms↗
PubMed1995

Height and mortality after myocardial infarction.

A case-control analysis was conducted to determine the relationship between height and mortality among patients enrolled in the already completed Beta Blocker Heart Attack Trial (BHAT). In a basic model including height (continuous) and relevant covariates the relative risk (RR) per 4-inch reduction in height (approximately 1 standard deviation) was 1.18 (95% confidence interval, 0.92 to 1.51). When sex was considered, the effect of short stature on mortality was found to be restricted to male subjects. The male RR per 4-inch reduction in height was 1.26 (0.96 to 1.63) whereas for women it was 0.89 (0.49 to 1.59). In males not randomized to propranolol (untreated) the effect was further modified with a RR per 4-inch reduction in height of 1.41 (1.00 to 1.99). It is hypothesized that short stature could be a marker for factors operating as far back as childhood that predispose males to mortality from coronary heart disease in later life.

Adult↗
PubMed1995

Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies.

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.

Adolescent↗
PubMed1994

Second cancers following oral and pharyngeal cancer: patients' characteristics and survival patterns.

A survey was made of second primary cancers among patients who were enrolled in a large case-control investigation of oral and pharyngeal cancer, hereafter called oral cancer, during 1984-1985 in four areas of the United States. Among the original 1090 patients with oral cancer (nearly all squamous cell carcinomas), 107 developed a second cancer (one-half of them squamous cell) by the end of follow-up in June 1989 (average follow-up 2.6 years), with 69% occurring in the oral cavity, pharynx, oesophagus, larynx or lung. Rates of second tumours varied by age and socioeconomic status, but not sex or race, and were higher among those whose initial cancer was localised, even after adjusting for their longer survival. Long-term survival was lower among those with second cancers. Conditional on surviving for 2 years, the survival at 5 years was under 50% and nearly 70%, respectively, for those with versus those without a second cancer in the first 2 years. These findings confirm the exceptionally high rate of second cancers (especially of the aerodigestive tract) following oral cancer, describe the clinical and pathological features of patients with multiple cancers and indicate the importance of preventive measures.

Adenocarcinoma↗
PubMed1994

Consumption of meat, animal products, protein, and fat and risk of breast cancer: a prospective cohort study in New York.

Epidemiologic studies have focused on the association between diet and breast cancer with conflicting results. Whereas a majority of case-control studies indicate a role for the intake of total fat and saturated fat, most prospective cohort studies either are negative or indicate very modest associations. Only a few authors have examined the role of meat intake in relation to breast cancer risk. The aim of this study was to examine the relation between risk of breast cancer and dietary intake of meat, animal products, fat, and protein. Between 1985 and 1991, we recruited 14,291 New York City women in a prospective cohort study of endogenous hormones, diet, and cancer in which they reported on their recent diet using a food frequency questionnaire self-administered at enrollment. From the cohort, 180 invasive breast cancer cases diagnosed before December 1990 and five times as many controls, individually matched by age, calendar time at enrollment, menopausal status, and, if premenopausal, phase of menstrual cycle, were included in a nested case-control study. There was an evident increase in the relative risk (RR) of breast cancer for increasing consumption of meat. Women in the upper quintile of meat consumption, as compared with the lowest quintile, had an energy-adjusted RR of 1.87 (95% confidence interval = 1.09-3.21). There was a modest RR increase in the upper quintile of total and saturated fat and no apparent association for other types of fat, protein, dairy products, poultry, or fish.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Use of human data in quantitative risk assessment of carcinogens: impact on epidemiologic practice and the regulatory process.

Epidemiologic data are increasingly being used to assess cancer risk from chemicals as their value is recognized and as more and better studies become available. Weight-of-evidence approaches are now available for classifying the experimental and epidemiological evidence regarding human carcinogenicity. When the human data are extensive and of good quality, they should be given substantial weight in assessing risk. Both the positive and the negative epidemiologic data should be used in a quantitative risk assessment (QRA), because only then can an unbiased risk assessment be derived. Good-quality epidemiological studies are those with sound methodology, lack of bias, long enough follow-up times to observe a carcinogenic response, adequate exposure information, and dose-response information. Before a lack of carcinogenicity can be inferred, it is essential that the exposures be of substantial duration and intensity, and that the number of exposed persons be reasonably large. Epidemiologists need to give more attention to exposure assessment, because lack of quantitative exposure information is often the limiting factor that prevents the use of epidemiologic data in QRA. Development of methods to estimate historical workplace exposure intensities from surrogate industrial hygiene variables should receive high research priority, since they have the potential to increase the usefulness in QRA of many epidemiologic studies that have limited exposure information. Several frequently used surrogates for exposure measurements have limitations or pitfalls in their use. In particular, the use of "ever/never" exposed has a large potential to produce falsely negative results by means of a "dilution" effect, especially in the common case where the exposure distribution is skewed. Duration of exposure (rather than duration x intensity) may also give misleading results. There is little information to suggest that synergistic exposures to multiple toxicants in an industrial environment are likely to invalidate QRAs, probably because few studies have identified a group of workers with major workplace exposures to multiple carcinogens that cause the same type of cancer. Most of the interactive effects which have been identified to date are between smoking and some occupational carcinogen, so this possibility needs careful evaluation for smoking-related diseases. It is important to evaluate dose-response gradients in a QRA to obtain maximum precision and accuracy in the resulting risk coefficient. The analysis should take into account an appropriate cancer induction period. Various methods to account for cancer induction times are compared; those that incorporate a lag period or model the induction-time distribution are superior to other methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinogens↗
PubMed1992

Intermittent ST depression and mortality after myocardial infarction.

BACKGROUND: We conducted a case-control analysis to determine the contribution made to mortality by intermittent ST depression (STD) among patients enrolled in the already completed Beta Blocker Heart Attack Trial. METHODS AND RESULTS: STD was determined by computer analysis of 24-hour ECG tapes as a change in ST level by +/- 0.1 mV or more from the median value of ST of all normally conducted complexes for greater than or equal to 1 minute. All computer-detected ST events were verified by trained readers. To estimate risk of dying associated with STD, 261 deaths were compared with controls matched for age, sex, drug status, and time elapsed since acute myocardial infarction. In a model including relevant covariates, STD had a relative risk (RR) of 1.73 (95% confidence interval, 1.09-2.73). The RR was 2.56 (1.39-4.71) in untreated patients and 0.98 (0.48-2.00) in propranolol-treated patients. A history of angina, although not independently significant, was found to enhance these RRs. A gradient of risk was shown in the placebo group by a RR of 1.91 in those with 1-30 minutes of STD and 4.33 in those with greater than 30 of STD (p = 0.001, trend test). CONCLUSIONS: The findings in this large study show a significant contribution to mortality among untreated early post-myocardial infarction survivors from transient STD on 24-hour monitoring. The absence or reduction of effect in the treated group also suggests an anti-ischemic mechanism by which propranolol exerts a protective effect on mortality. Trials to determine whether reduction of STD improves survival would be warranted.

Adult↗
PubMed1992

Issues and epidemiological evidence regarding radiation-induced thyroid cancer.

The available information on the induction of thyroid cancer in humans by ionizing radiation is summarized and weaknesses or gaps in assessing risk are identified. Issues to be addressed include: average estimates of thyroid cancer risk from external irradiation, the effects of age on thyroid cancer induction, shape of the dose-response curve for acute irradiation, magnitude of risk at low doses, effects of dose fractionation or dose protraction, the relative effectiveness of iodine-131 (131I) in inducing thyroid cancer compared to external radiation, the temporal course of radiogenic thyroid cancer risk, mortality caused by thyroid cancer, host-susceptibility factors for radiogenic thyroid cancer, and biological factors in risk. It is concluded that the most important needs are to obtain more information on thyroid cancer risks following low-level or highly fractionated radiation exposures and following 131I exposure in children.

Age Factors↗
PubMed1991

Hair dye use and breast cancer: a case-control study among screening participants.

To investigate whether hair dye use increases the risk of breast cancer, a case-control study was conducted among patients attending a screening center in New York City. The study group consisted of 398 breast cancer cases identified at the screening center between 1977 and 1981, and 790 randomly selected controls screened during the same period. Subjects were interviewed by telephone to obtain information on known risk factors for breast cancer, along with a complete history of hair dye use detailing type of dye, color, duration, frequency, and temporal periods of use. Most subjects (77%) had used hair dye at least once, 38% of the subjects at least 100 times. However, little increased risk of breast cancer was found among hair dye users. The adjusted odds ratio for ever having used hair dye was 0.8 (95% confidence interval 0.6-1.1), and there was no evidence of a trend in risk with increasing number of hair dye uses. The results were the same whether all past exposures were considered or only exposures more than 10 years before disease. Breast cancer risk did not increase with increasing intensity of exposure, as measured by frequency of use or darkness of color. No effect was seen for different types or colors of dye, or for use during different periods of reproductive life. Although personal hair dye use was unrelated to breast cancer risk, there was an adjusted odds ratio of 3.0 (95% confidence interval 1.1-7.8) for 5 or more years of work as a beautician. Overall, the results of this study, taken in conjunction with the findings of other epidemiologic studies, do not implicate hair dye use as an important cause of human breast cancer.

Adult↗
PubMed1991

Endogenous hormones and breast cancer: a prospective cohort study.

A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far.

Adult↗
PubMed1991

Time variations in the risk of cancer following irradiation in childhood.

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model.

Adolescent↗
PubMed1990

Second malignancies following radiotherapy for testicular seminoma.

Traditional treatment for testicular seminoma produces excellent survival. We report five, second non-testicular malignancies which occurred in a group of seminoma patients. A total of 79 men with primary testicular seminoma were available for analysis. All underwent a radical inguinal orchiectomy. Those with Stage I disease received adjuvant radiation therapy to the para-aortic and ipsilateral iliac nodes. The usual dose was 2500 cGy in 15 treatments. Stage II patients also received prophylactic mediastinal radiation therapy to a dose of 2500 cGy. None of the 51 Stage II patients died of tumour, whereas four of the 28 Stage II patients died of their disease. The median follow-up was ten years (range 4-25 years). The second malignancies seen were melanoma (2), myeloma, caecal adenocarcinoma, and retroperitoneal fibrosarcoma. All but one tumour developed within the radiation fields. Based on US SEER data for white males, only 1.5 cancers were expected, giving significantly greater (P = 0.04) relative risk. This observation lends support to observation, rather than elective treatment, in patients with Stage I testicular cancer.

Dysgerminoma↗
PubMed1990

Overview of radiation-induced skin cancer in humans.

There are about a dozen studies of the incidence of skin cancer among irradiated populations with known skin doses that are available for estimating the risk of radiation-induced skin cancer. It is of note that they provide no evidence for a dose threshold and are compatible with a linear dose-response relationship, at least for ultraviolet radiation exposed skin. The studies also provide varying amounts of evidence concerning a number of other important issues in assessing skin cancer risk: types of skin cancer induced by ionizing radiation, the appropriateness of relative risk vs absolute risk models, combined effects of ionizing and UV radiations, and variations in sensitivity to skin cancer induction among demographic and genetic subgroups. Little epidemiological information is available on several factors, such as the RBE for high-LET radiation, the effects of dose protraction or fractionation, or variations in risk by age at irradiation. A reasonable estimate of skin cancer lethality was 0.2 per cent when weighted for the relative proportions of squamous cell and basal cell skin cancers. Average risk estimates of radiation-induced skin cancer incidence were: absolute risk (AR) of 8.5 X 10(-4) person-year-Sv and excess relative risk (RR) of 52 per cent/Sv. Lifetime skin cancer risk was calculated by life-table methods for males from exposures spread out over ages 20-60 years. The estimates for excess skin cancer incidence were 2 per cent and 11 per cent per Sv under the AR and RR models, respectively, while the corresponding mortality risks were 4 X 10(-5) and 2 X 10(-4) per Sv.

Environmental Exposure↗
PubMed1990

Occupational radiation studies: status, problems, and prospects.

At least 350,000 workers at U.S. radiation facilities are being followed up to monitor their mortality experience, with particular reference to cancer. Although these studies are expensive, they are needed from the standpoint of public health and radiation protection; they also provide a useful check that the risk extrapolation models based on high dose data are not seriously out of line. Unfortunately, there are a number of problems in interpreting radiation worker studies that stem mainly from the fact that the expected magnitude of effects is small because of the low doses. Problems of falsely positive effects caused by chance or by study biases are difficult to distinguish from real effects. Dose-effect analyses and pooled analyses from several studies offer some improvements in assessing the risk from low doses but do not obviate all the problems. Future studies should explore whether there are biological markers of exposure, damage, or susceptibility that would improve our power to assess individual risk.

Dose-Response Relationship, Radiation↗
PubMed1990

Men assigned to ethylene oxide production or other ethylene oxide related chemical manufacturing: a mortality study.

A retrospective cohort study was conducted to examine the mortality experience of 2174 men employed between 1940 and 1978 by a large chemical company and who had been assigned to a chemical production department that used or produced ethylene oxide (EO). Comparisons were made with the general United States population, the regional population, and with a group of 26,965 unexposed men from the same plants. Comparisons with general United States death rates showed fewer deaths than expected in the EO group due to all causes and for total cancers. There was no statistically significant excess of deaths due to any cause. Seven deaths each due to leukaemia and pancreatic cancer were observed with 3.0 and 4.1 deaths expected. Among the subcohort of men who worked where both average and peak exposure levels were probably highest, however, one death due to pancreatic cancer (0.9 expected) and no deaths due to leukaemia were observed. Four of the seven who died from leukaemia and six of the seven who died from pancreatic cancer had been assigned to the chlorohydrin department where the potential for exposure to EO is judged to have been low. The relative risk of death due to each disease was strongly related to duration of assignments to that department. When men who worked in the chlorohydrin department were excluded, there was no evidence for an association of exposure to EO with pancreatic cancer or leukaemia. Together with the failure to show independent EO associations, the chlorohydrin department results suggest that leukaemia and pancreatic cancer may have been associated primarily with production of ethylene chlorohydrin or propylene chlorohydrin, or both. These results emphasise the importance of examining additional concurrent/asynchronous exposures among human populations exposed to EO.

Adult↗
PubMed1989

The risk of breast cancer after irradiation of the thymus in infancy.

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

Adult↗