Antioxidant vitamins, cancer, and cardiovascular disease.
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Antioxidants↗
Biomedical subjects
E R Greenberg
Publications and source records attributed to E R Greenberg.
Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation.
OBJECTIVE: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. DESIGN: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. SETTING: Medical school-affiliated dermatology practices. PATIENTS: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. INTERVENTION: Oral beta carotene, 50 mg per day for a median of 4.3 years. MAIN OUTCOME MEASURES: All-cause mortality and mortality from cardiovascular disease and cancer. RESULTS: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. CONCLUSIONS: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.
Administration, Oral↗
Regional differences in the incidence and treatment of carcinoma in situ of the breast.
Greater use of mammography in the United States in recent years has increased the detection of early neoplasms of the breast, including carcinoma in situ. However, the occurrence and treatment of diagnosed carcinoma in situ of the breast has not been fully described. Our goal was to examine temporal, geographic, and demographic patterns in the incidence and treatment of in situ breast cancer. The study included data from all women with in situ breast cancer that had been detected in the nine Surveillance, Epidemiology, and End Results areas of the United States from 1975 through 1990 (Surveillance Program, Cancer Statistics Branch, Bethesda, MD: National Cancer Institute, November, 1993). We calculated age-adjusted incidence rates (1970 United States standard) using data on histology and treatment from the Surveillance, Epidemiology, and End Results data tape. We assessed predictors of treatment by mastectomy using multiple logistic regression. From 1975-1979 to 1986-1990, the age-adjusted incidence rate of in situ breast cancer increased from 4.7 to 16.9/100,000 women. The increase occurred in all age groups and among both white and black women. However, there was nearly a 2-fold difference in incidence rates across geographic areas in 1986-1990, ranging from < 12/100,000 in Iowa and New Mexico to > 20/100,000 in San Francisco and Seattle. Geographic variability in treatment was also evident, with mastectomy, rather than breast-conserving therapy, performed on 46% of the women with in situ breast cancer in San Francisco and on 66% of those in Iowa. The incidence of diagnosed in situ breast cancer increased markedly during the 1980s, and there was substantial geographic variability in the rates of detection of these tumors and in the type of therapy received. Although mastectomy became a less common treatment over time, it was still performed on a high proportion of women with in situ breast cancer during the latter part of the decade.
Adult↗
Reliability of whole crypt mitotic count as a measure of cellular proliferation in rectal biopsies.
We conducted a reliability study of whole crypt mitotic count, a measure of cellular proliferation with potential use as an intermediate marker in studies of colorectal cancer risk and prevention. The study involved biopsies taken from two distinct locations at 8-10 cm from the anal verge for 20 subjects scheduled to undergo routine endoscopy. In addition to the overall count of mitoses per crypt (mitotic count), we investigated two novel measures based on the percentages of heights of mitotic cells within crypts: the mean height, and the maximum minus minimum (max - min) height of mitoses. The max - min height was positively correlated with mitotic count (r = 0.64); however, there was little correlation between mitotic count and the mean height of mitotic cells (r = 0.12). Components of variance were estimated for the three measures; for mitotic count and max - min height, the variability between persons was substantially greater than that between locations within an individual. For mean height, the between-person and between-location variabilities were roughly equal. These results suggest that whole crypt mitotic count has promise as a reliable measure of rectal cellular proliferation, but further studies will be necessary to assess the utility of this assay.
Adult↗
Risk of breast cancer in relation to lifetime alcohol consumption.
BACKGROUND: Although an association between alcohol consumption and risk of breast cancer has been observed in many studies, questions of major importance remain, including the nature of the dose-response relationship and the effects of drinking at various periods in life. PURPOSE: Our goal was to address the issues listed above with a large case-control study. METHODS: We conducted a population-based case-control study in Maine, Massachusetts (excluding the four counties that include metropolitan Boston), New Hampshire, and Wisconsin. Case patients were eligible if their diagnosis of invasive breast cancer was first reported to one of the four statewide cancer registries during the period of 1988 through 1991. During the accrual period, 11,879 potentially eligible case patients and 16,217 control subjects were identified. After excluding ineligible women from the study, telephone interviews were obtained from 6888 case patients and 9424 control subjects. Complete data for recent alcohol consumption, and thus final eligibility for study participation, were determined for 6662 case patients and 9163 control subjects. The average age at time of interview was 58.7 years. The questions on alcohol use addressed average consumption during five periods of the subjects' lives: ages 16-19, 20-29, 30-39, 40-59, and 60-74 years. Similar responses from 211 control subjects upon reinterview 6-12 months later were taken to be indicative of the reliability of the questionnaire used in this study. RESULTS: Lifetime average alcohol consumption (measured as the average grams per day consumed from age 16 to the recent past) and recent alcohol consumption (average grams per day consumed in the previous age interval) were associated with risk of developing breast cancer. The multivariate relative risk of breast cancer, in those who drink compared with abstainers, associated with average lifetime consumption of 12-18 g/day of alcohol (about one drink) was 1.39 (95% confidence interval [CI] = 1.16-1.67), of 19-32 g/day (about two drinks) was 1.69 (95% CI = 1.36-2.10), of 33-45 g/day (about three drinks) was 2.30 (95% CI = 1.51-3.51), and of greater than or equal to 46 g/day (four or more drinks) was 1.75 (95% CI = 1.16-2.64) (P for trend < .0001). The multivariate relative risk per 13 g/day (about one drink) of alcohol consumed before 30 years of age was 1.09 (95% CI = 0.95-1.24), whereas the relative risk associated with recent consumption of 13 g/day was 1.21 (95% CI = 1.09-1.34). CONCLUSIONS: In these data, alcohol consumption was clearly related to breast cancer risk. Risk appeared to increase even at moderate levels of consumption. For women of all ages combined, consumption before 30 years of age was not an important determinant of risk.
Adolescent↗
Long-term morbidity following jejunoileal bypass. The continuing potential need for surgical reversal.
OBJECTIVE: To review the late sequelae of jejunoileal bypass (JIB) and the potential role of late surgical reversal in ameliorating morbidity and mortality following JIB. DESIGN: Patients who underwent JIB between 1965 and 1977 were contacted and pertinent health-event information was gathered. Early sequelae were defined as disorders occurring within the first 2 years after JIB; late sequelae were those occurring after 2 years. Health events occurring between 0 and 23 years after JIB were documented. SETTING: A private, tertiary referral center. PATIENTS: Patients underwent JIB for morbid obesity that had failed medical and/or psychiatric interventions. MAIN OUTCOME MEASURES: Body mass index (BMI) (weight kilograms divided by the square of the height in meters), diarrhea, electrolyte imbalance, acute, and chronic liver disease, renal disease, JIB reversal, reason for JIB reversal, death, and cause of death. RESULTS: A total of 453 morbidity obese patients underwent JIB. By 2 years following JIB, the mean (+/- SD) BMI dropped from 49.3 +/- 8.1 to 31.1 +/- 0.8 and remained at this level until year 15, after which weight gradually increased (BMI, 35.4 +/- 3.1). The most severe early complication was acute liver failure, which occurred in 7% of patients and caused seven deaths. At 15 years, the actuarial probability of the most common serious late complications related to JIB were renal disease (37%), with two deaths; diarrhea (29%); and liver disease (10%), with three deaths. One hundred thirty-eight patients (31%) had a bypass reversal. The most common indications for reversal were diarrhea and electrolyte disturbance (29%), renal disease (19%), and liver disease (17%). Fifty-six patients died more than 30 days after JIB: 64% before JIB reversal, 13% at the time of reversal, and 23% subsequently. CONCLUSIONS: Jejunoileal bypass is associated with progressive accrual of serious, sometimes life-threatening complications. Lifelong follow-up for early diagnosis and surgical reversal before life is threatened should reduce the morbidity and mortality associated with this procedure.
Acid-Base Imbalance↗
Strenuous physical activity in young adulthood and risk of breast cancer (United States).
The epidemiologic data on the relation between strenuous physical activity and breast cancer are limited and inconsistent. Because risk of breast cancer may be influenced by ovarian function which, in turn is modulated by physical activity, the hypothesis that exercise may be associated with a reduced risk of breast cancer merits further investigation. We, therefore, conducted a large case-control study in 1988-1991, and interviewed 6,888 women (17 to 74 years of age) with breast cancer in Maine, Massachusetts, New Hampshire, and Wisconsin (United States). Interviewed controls (9,539 women, 18 to 74 years of age) were selected randomly from lists of licensed drivers (for younger women) or from a roster of Medicare enrollees (for older women). We used multivariate adjusted odds ratios (OR) and 95 percent confidence intervals (CI) from logistic regression models to estimate relative risks between self-reported physical activity when 14 to 22 years of age and breast cancer. When compared with sedentary controls, women who reported any strenuous physical during ages 14 to 22 years had a modest reduction in the risk of breast cancer (OR = 0.95, CI = 0.93-0.97). However, those who exercised vigorously at least once a day had a 50 percent reduction in risk of breast cancer (OR = 0.5, CI = 0.4-0.7). These data support the hypothesis that women who are physically active have a reduced risk of breast cancer.
Adolescent↗
Nonsteroidal antiinflammatory drugs and human cancer. Report of an interdisciplinary research workshop.
BACKGROUND: Since the 1970s, work in several disciplines (toxicology, pharmacology, clinical medicine, epidemiology) increasingly has suggested that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may reduce the occurrence or progression of colorectal cancers and polyps and perhaps of other gastrointestinal tumors. The potential application of these findings for chemoprevention of such cancers in man now deserves serious consideration. METHODS: An interdisciplinary workshop was held by the American Cancer Society in March 1994 to review the current knowledge of NSAIDs and cancer and to seek a consensus on future research directions, particularly concerning the possibility of randomized prevention trials in human populations. RESULTS: A wide-ranging review was conducted of past and current research regarding (1) NSAIDs' effects in experimental animal cancer models; (2) clinic experience in NSAID treatment, particularly in familial polyposis; (3) pharmacologic studies regarding the enzymatic and metabolic actions of NSAIDs; and (4) epidemiologic observations on the relationship of aspirin/NSAID usage to colorectal cancer occurrence in human populations. CONCLUSIONS: Combined evidence from different research disciplines strongly supports the notion that aspirin and other NSAIDs act to prevent the development or progression of certain human gastrointestinal cancers, especially colorectal cancer. Consequently, the workshop recommended that randomized prevention trials be undertaken. For various logistic reasons, such trials probably should focus on NSAID effects on the occurrence and progression of colorectal polyps rather than on carcinoma itself. Continued research also is needed to clarify further the pharmacologic, clinical, and epidemiologic nature of NSAIDs' influences on human carcinogenesis.
Animals↗
A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group.
BACKGROUND: People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. METHODS: We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. RESULTS: Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS: The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.
Adenomatous Polyps↗
Changes in prostate cancer incidence and treatment in USA.
We examined time trends and geographical variations in the detection and treatment of prostate cancer in USA, based on information from white men aged 50 to 79 who resided in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program of the United States National Cancer Institute. Prostate-cancer incidence and treatment rates were determined for the 9 population-based cancer registries which participate in the SEER program. Prostate-cancer mortality rates were assessed from data compiled by the National Center for Health Statistics. Prostate cancer incidence rates increased by 6.4% per year between 1983 and 1989. The increase appeared to be due to detection of early-stage disease; there was no increase in the incidence rate of metastatic cancer. Incidence rates varied widely among the SEER program areas: in 1989 from 267.9 per 100,000 in Connecticut to 606.8 in Seattle. Radical prostatectomy rates more than tripled between 1983 and 1989 in the SEER areas as a whole. Among men aged 70-79, the rate of prostatectomy increased by nearly 35% per year. There was a five-fold variation among SEER areas in radical prostatectomy rates in 1989, with a low of 43.4 per 100,000 in Connecticut and a high of 224.4 in Seattle. Prostate cancer mortality rates did not increase during the period of study; there was little variation among areas in prostate-cancer mortality rates, and no apparent correlation between the incidence and mortality rates for an area. Increases in rates of prostate cancer incidence and prostate surgery have occurred in the United States without clear evidence that screening and prostectomy are effective in reducing mortality. Moreover, much of the growth in incidence and radical prostatectomy rates has occurred among older men, who appear least likely to benefit from early detection and surgery of occult prostate cancer.
Aged↗
Steady-state serum concentration of alpha tocopherol not altered by supplementation with oral beta carotene. The Polyp Prevention Study 1 Group.
BACKGROUND: The antioxidants beta carotene and vitamin E may play a role in cancer prevention. However, some studies have suggested that oral supplements of beta carotene may cause a decrease in serum levels of alpha tocopherol (vitamin E). PURPOSE: We conducted this study to determine if beta carotene supplements affect serum levels of vitamin E and vice versa. METHODS: Five hundred five patients in a clinical trial of antioxidant vitamins, used to prevent recurrences of colonic polyps, received either a placebo, 25 mg of beta carotene per day, 1 g ascorbic acid plus 400 mg alpha tocopherol per day, or all three agents combined. Serum levels of beta carotene and vitamin E were measured before and after 9 months of supplementation, using high-performance liquid chromatography. RESULTS: Vitamin E levels changed very little among the groups receiving placebo or beta carotene and went up substantially and equally in the groups receiving vitamin E plus ascorbic acid or all three agents together. Conversely, beta carotene levels changed very little for the groups receiving placebo or ascorbic acid plus vitamin E but went up substantially and equally for the groups receiving beta carotene alone or all three agents. CONCLUSIONS: We conclude that oral supplementation with beta carotene for 9 months does not alter serum concentration of vitamin E and that supplementation with vitamin E plus ascorbic acid does not alter serum beta carotene levels.
Administration, Oral↗
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↗
Carotenoids, cigarette smoking, and mortality risk.
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Adult↗
Statistical methods in research.
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Age Factors↗
Prospects for preventing colorectal cancer death.
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Aged↗
Reduced risk of large-bowel adenomas among aspirin users. The Polyp Prevention Study Group.
BACKGROUND: Epidemiological studies have indicated that aspirin consumption can lower the risk of large-bowel cancer. These studies are not entirely consistent, however, and their interpretation has been complicated by the possibility that cancer symptoms may have led patients to avoid aspirin or that aspirin may have influenced cancer diagnosis and treatment. PURPOSE: Our purpose was to determine the effect of aspirin on risk of large-bowel neoplasms in a study in which aspirin use would not be expected to affect tumor detection and tumor-related symptoms would not likely influence aspirin use. A less complicated assessment of the relationship between aspirin and large-bowel tumors should thus be possible. METHODS: We studied 793 patients enrolled in a clinical trial of nutrient supplements to prevent large-bowel adenomas. Unlike invasive cancers, adenomas usually do not cause symptoms or detectable gastrointestinal bleeding; thus, adenomas are unlikely to influence aspirin use. Each patient had at least one large-bowel adenoma diagnosed and removed shortly before study entry and had been judged to be free of further tumors by colonoscopy. Use of aspirin was assessed by responses on questionnaires administered 6 and 12 months after enrollment. We performed complete colonoscopies on all patients 1 year after they entered the study and removed all polyps. RESULTS: Patients who reported taking aspirin on both questionnaires (consistent users) had a lower risk of new adenomas at their 1-year follow-up colonoscopy (odds ratio = 0.52; 95% confidence interval = 0.31-0.89) compared with patients who did not report using aspirin on either of the questionnaires. The apparent protective effect of consistent aspirin use was present among both men and women and did not appear to be influenced by the number of prior adenomas. CONCLUSIONS: These data further support the hypothesis that aspirin has an antineoplastic effect in the large bowel. Nevertheless, the question of whether aspirin should be used to prevent large-bowel tumors would be best answered by a randomized controlled clinical trial specifically designed to address this issue.
Adenoma↗
Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up.
OBJECTIVE: Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy. DESIGN: Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records. PARTICIPANTS: Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women. MAIN OUTCOME MEASURES: Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates. MAIN RESULTS: The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence. CONCLUSION: Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.
Abortion, Spontaneous↗
Retinoids or carotenoids: is there another choice?
Both retinoids and carotenoids decrease cancer occurrence in selected animal models of carcinogenesis, but the retinoids appear to have more potent activity against a wider variety of tumors. Further use of retinoids for cancer prevention will be limited, however, because of their toxic effects on bone and skin (among other organs). In contrast to retinoids, carotenoids seem to be free of important toxicity and this fact makes them more promising for use in the general adult population. However, the idea that carotenoids have a cancer-preventive effect in humans is based almost entirely on epidemiological studies of diet and serum which could simply reflect the effects of some other dietary constituents. In the search to explain the profoundly lower risk of death associated with eating a diet high in fruits, vegetables, and grains, there is a place for clinical trials testing one specific nutrient, such as beta-carotene, against one disease, such as lung cancer, but we should not rely exclusively on these narrowly focused studies. In addition, careful analyses of cohort studies may reveal broad patterns of diet that are associated with lower mortality. These diets can then be tested in clinical trials for their efficacy against a variety of causes of death and disability. For now, the most rational and prudent choice would be to consume a diet high in fruits, vegetables, and grains and not to take either supplemental antioxidants or retinoids until there is clear evidence of their effectiveness and safety.
Animals↗