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Biomedical subjects

R E Shore

Publications and source records attributed to R E Shore.

At least 55 records · Page 3Linked to original sources

Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women.

A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer.

Aged↗

Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle.

Levels of total estradiol in premenopausal women vary widely over the course of the menstrual cycle with a spike at the time of ovulation and dissimilar patterns pre- and post-ovulation. Evaluating the association between breast cancer and premenopausal measurements of total estradiol when the measurements cannot be taken on a uniform day of the cycle is therefore a difficult methodological challenge. In a matched case-control study of breast cancer nested within a prospective study, premenopausal serum samples obtained up to 7 years before breast cancer diagnosis were available for total estradiol assay. By fitting a three-piece spline model that regressed the logarithm of total estradiol (ln estradiol) on day of menstrual cycle, the authors were able to adjust the measurements for day of the cycle on which they were collected by expressing them in terms of the number of standard deviations above or below the fitted ln estradiol value for that day. Applying the adjusted measurements to the nested case-control study, they found evidence of a 1.5 to 2-fold risk for women in the upper two tertiles of ln estradiol relative to women in the lowest tertile. Conditional logistic regression analysis for day-of-cycle-adjusted ln estradiol treated as a continuous variable resulted in a relative risk estimate of 1.19 (95% confidence interval 0.91-1.55) per standard-deviation increase in adjusted ln estradiol.

Adult↗

Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol.

BACKGROUND: The exceptionally high rate of second primary cancers among patients with oral and pharyngeal cancers is well recognized, yet there has been limited epidemiologic study of risk factors for second tumors. PURPOSE: To evaluate the relation of smoking and alcohol consumption to the development of second cancers among this high-risk patient group, we conducted a nested case-control study. METHODS: A total of 1090 patients enrolled in a 1984-1985 population-based, case-control study of oral cancer in four areas of the United States were followed through June 1989 for the occurrence of second primary cancers. Information on tobacco and alcohol consumption was obtained from the original interviews and was updated by follow-up interviews obtained for 80 case patients with second cancers and 189 sex-, study area-, and survival-matched cancer patients free of second cancers (control subjects). RESULTS: Tobacco smoking and alcohol drinking each contributed to risk of second cancers, with the effects of smoking more pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for alcohol) rose with duration and intensity of smoking and were strongest for tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as of the baseline survey experienced a fourfold increased risk of a second aerodigestive tract cancer relative to nonsmokers and former smokers. No reduction in risk was associated with cessation of smoking or drinking at or after the index diagnosis, although the short median interval (27 months) between tumor diagnoses limited observation of the effects due to recent cessation. Risk was significantly reduced, however, 5 years after smoking cessation. Among drinkers, second cancer risk was greatest for beer intake, with an OR for a second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers per week. CONCLUSIONS: Oral and pharyngeal cancer patients with the highest intakes of tobacco and alcohol are the ones most prone to develop second primary cancers. IMPLICATIONS: Avoidance of tobacco smoking and alcohol drinking is the most desirable way not only to prevent primary oral cancers, but also to reduce risk of second cancers of the aerodigestive system.

Aged↗

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↗

Dietary factors and second primary cancers: a follow-up of oral and pharyngeal cancer patients.

To investigate the possible relationship between dietary factors and the development of multiple primary cancer, a nested case-control study was carried out within a cohort of 1,090 oral and pharyngeal cancer patients. This patient group, enrolled in 1984-1985 in a population-based case-control study conducted in four areas of the United States, was followed up through June 1989 for the occurrence of second primary cancer. Information on a number of risk factors, including diet, ascertained from interviews conducted at baseline (1984-1985) and at follow-up were compared between 80 patients with histologically confirmed second primary cancers (39% in the upper aerodigestive tract, 32% in the lung, 29% elsewhere) and 189 sex- and survival-matched control patients free of second cancers. Although few significant trends emerged, the results were suggestive of a protective effect provided by higher intake of vegetables. Risk of second primary cancers was 40-60% lower among those with the highest levels of intake for total vegetables and most vegetable subgroups, including dark yellow, cruciferous, and green leafy vegetables and legumes. Risks were also nonsignificantly lower among those with high consumption of vitamin C and carotenoids, with the adverse effects of alcohol being most evident among heavy drinkers with low vitamin C or carotenoid intake. There was also some evidence of an interaction between smoking and vitamin C consumption, but numbers of nonsmokers were small. Among other dietary factors considered, positive associations were found with increasing consumption of meats, liver, and retinol. The findings suggest that dietary factors contribute along with alcohol and smoking to the excess risks of second primary cancers among patients with oral and pharyngeal cancers.

Aged↗

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↗

Thyroid cancer among persons given X-ray treatment in infancy for an enlarged thymus gland.

A cohort of 2,657 infants in Rochester, New York, who were given x-ray treatment for a purported enlarged thymus gland, along with 4,833 siblings, have been followed by mail surveys through about 1986, which represents an average of 37 years of follow-up, to determine their incidence of thyroid cancer. Estimated thyroid doses ranged from 0.03 to > 10 Gy, with 62% receiving > 0.5 Gy. There were 37 pathologically diagnosed thyroid cancers in the irradiated group and five in the sibling controls. The dose-response relation was essentially linear, with no evidence of an additional dose-squared component. The estimated relative risk at 1 Gy was 10 (90% confidence interval 5-23). Thyroid cancer rates were elevated even at low doses; i.e., a dose-response analysis over the range of 0-0.3 Gy showed a significant positive slope. The risk ratio was declining over time but was still highly elevated to at least 45 years after irradiation. An examination of potential risk factors showed that older age at first childbirth was significantly associated with thyroid cancer risk. An evaluation of interactions between possible risk factors and radiation suggested that Jewish subjects and women with older ages at menarche or at first childbirth were at greater risk for radiogenic thyroid cancer.

Age Factors↗

The influence of medical conditions associated with hormones on the risk of breast cancer.

Medical conditions related to hormonal abnormalities were investigated in a case-control study of breast cancer among women who attended a screening centre. Information was obtained by telephone interview regarding physician-diagnosed medical conditions such as thyroid or liver diseases, diabetes, and hypertension, as well as hirsutism, acne, galactorrhoea, and reproductive, menstrual, and gynaecological factors. Results are presented for 354 cases and 747 controls. Women with fertility problems who never succeeded in becoming pregnant were at significantly increased breast cancer risk (adjusted odds ratio [OR] = 3.5; 95% confidence interval [CI]:1.1-10.9). An elevated cancer risk was also associated with having excess body hair (OR = 1.5; 95% CI:1.0-2.3), or having excess body hair in addition to persistent adult acne (OR = 6.8; 95% CI:1.7-27.1). Recurrent amenorrhea (OR = 3.5; 95% CI:1.1-11.5), and a treated hyperthyroid condition (OR = 2.2; 95% CI:1.1-4.4) were significantly associated with risk. A non-significant elevation of risk was present for endometrial hyperplasia (OR = 1.8; 95% CI: 0.8-4.0). There was a suggestion of an association between a history of galactorrhoea and breast cancer risk (OR = 2.0; 95% CI:0.8-4.9) among premenopausal women. No associations were found with other medical or gynaecological factors. The possibility that some of these findings are due to chance cannot be excluded because of the problem of multiple comparisons.

Abortion, Spontaneous↗

Ethylene oxide: an assessment of the epidemiological evidence on carcinogenicity.

Mortality from cancer among workers exposed to ethylene oxide (EtO) has been studied in 10 distinct cohorts that include about 29,800 workers and 2540 deaths. This paper presents a review and meta-analysis of these studies, primarily for leukaemia, non-Hodgkin's lymphoma, stomach cancer, pancreatic cancer, and cancer of the brain and nervous system. The magnitude and consistency of the standardised mortality ratios (SMRs) were evaluated for the individual and combined studies, as well as trends by intensity or frequency of exposure, by duration of exposure, and by latency (time since first exposure). Exposures to other workplace chemicals were examined as possible confounder variables. Three small studies by Hogstedt initially suggested an association between EtO and leukaemia, but in seven subsequent studies the SMRs for leukaemia have been much lower. For the combined studies the SMR = 1.06 (95% confidence interval (95% CI) 0.73-1.48). There was a slight suggestion of a trend by duration of exposure (p = 0.19) and a suggested increase with longer latency (p = 0.07), but there was no overall trend in risk of leukaemia by intensity or frequency of exposure; nor did a cumulative exposure analysis in the largest study indicate a quantitative association. There was also an indication that in two studies with increased risks the workers had been exposed to other potential carcinogens. For non-Hodgkin's lymphoma there was a suggestive risk overall (SMR = 1.35, 95% CI 0.93-1.90). Breakdowns by exposure intensity or frequency, exposure duration, or latency did not indicate an association, but a positive trend by cumulative exposure (p = 0.05) was seen in the largest study. There was a suggested increase in the overall SMR for stomach cancer (SMR = 1.28, 95% CI 0.98-1.65 (CI 0.73-2.26 when heterogeneity among the risk estimates was taken into account)), but analyses by intensity or duration of exposure or cumulative exposure did not support a causal association for stomach cancer. The overall SMRs and exposure-response analyses did not indicate a risk from EtO for pancreatic cancer (SMR = 0.98), brain and nervous system cancer (SMR = 0.89), or total cancer (SMR = 0.94). Although the current data do not provide consistent and convincing evidence that EtO causes leukaemia or non-Hodgkin's lymphoma, the issues are not resolved and await further studies of exposed populations.

Ethylene Oxide↗

Benign thyroid adenomas among persons X-irradiated in infancy for enlarged thymus glands.

Thyroid adenoma incidence in a cohort of 2657 infants given X-ray treatment for a supposedly enlarged thymus gland, along with 4833 unirradiated siblings, has been ascertained for an average of 37 years since irradiation. Estimated thyroid doses ranged from 0.03 to > 8 Gy, with 62% receiving < 0.5 Gy. After excluding 4 adenoma cases with concurrent or previous thyroid cancer, there were 86 cases with pathologically diagnosed thyroid adenomas in the irradiated group and 11 in the sibling controls. The estimated excess relative risk (ERR) was 6.3 per gray (90% CI = 3.7, 11.2). Once the dose group with > or = 6 Gy, which was producing downward curvature in the dose-response function, was removed, the curve was compatible with linearity and the ERR was 7.8 per gray. Thyroid adenoma rates were elevated even at low doses: the lowest dose group (< 0.25 Gy) showed a significant elevation in risk. The relative risk appeared to be constant over time and was comparable for both sexes. Excess adenoma risk was observed in the irradiated group to the maximum follow-up interval of about 50 years. A number of potential risk factors for thyroid adenoma were examined both as risk factors in their own right and as modifiers of the radiogenic risk. Parity and use of hormones in relation to menopause were significantly associated with thyroid adenoma risk in women, while education, Jewish origin, history of hyperthyroidism or hypothyroidism, and family history of cancer were also adenoma risk factors in both sexes. An examination of interactions between possible risk factors and radiation suggested that women with a history of oral contraceptive use or hysterectomy and persons with a family history of cancer may have greater risk (per unit dose) of radiogenic thyroid adenomas than their counterparts.

Adenoma↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗