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Biomedical subjects

J E Manson

Publications and source records attributed to J E Manson.

At least 163 records · Page 9Linked to original sources

Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.

OBJECTIVE: To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN: Cohort study. SETTING: In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME MEASURE: Non-insulin-dependent diabetes mellitus. RESULTS: During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.

Adult↗

Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians.

BACKGROUND: Moderate alcohol consumption decreases the risk of coronary heart disease, but its relation to peripheral arterial disease (PAD) is uncertain. METHODS AND RESULTS: In the Physicians' Health Study, a randomized trial of the use of aspirin and beta-carotene in 22071 apparently healthy men, we documented 433 incident cases of PAD during 11 years of follow-up. After we controlled for age and treatment assignment, daily drinkers (> or = 7 drinks per week) had a relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17) compared with the reference group (< 1 drink per week). After additional control for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for exercise, diabetes mellitus, and parental history of myocardial infarction revealed an RR of 0.74 (0.57 to 0.97). CONCLUSIONS: Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men.

Adult↗

Prospective study of moderate alcohol consumption and mortality in US male physicians.

BACKGROUND: Although moderate alcohol consumption decreases the risk of myocardial infarction, its impact on all-cause mortality among apparently healthy men is unclear. METHODS: We performed a prospective cohort study in 22071 men in the Physicians' Health Study. Participants were aged 40 to 84 years and had no history of myocardial infarction, stroke, transient ischemic attack, or cancer. RESULTS: There were 1206 deaths (394 cardiovascular, 488 cancer, and 324 other) during 10.7 years of follow-up. Compared with participants who consumed less than 1 drink per week, the relative risk (95% confidence interval) of all-cause mortality for men who consumed 2 to 4 drinks per week was 0.72 (0.59-0.87); 5 to 6 drinks per week, 0.79 (0.64-0.99); 1 drink per day, 0.98 (0.84-1.15); and the highest drinking group (> or = 2 drinks per day), 1.51 (1.17-1.95). This association was similar with either nondrinkers or occasional drinkers used as the reference group and was not subject to material confounding or effect modification by any factor examined. The overall relationship was the result of a J-shaped association with cardiovascular mortality, an increase in cancer deaths for the highest drinking group, and a U-shaped association with other causes of mortality. CONCLUSIONS: Risk of all-cause mortality varies by level of alcohol consumption. In this apparently healthy cohort, men who consumed 2 to 6 drinks per week had the most favorable mortality profile and men who had 2 or more drinks per day the most unfavorable mortality profile. The difference between consumption of small and large amounts of alcohol may mean the difference between preventing and causing excess mortality.

Adult↗

Reproducibility of oral contraceptive histories and validity of hormone composition reported in a cohort of US women.

Histories of oral contraceptive (OC) use were reported by 116,686 women aged 25 to 42 years in the Nurses' Health Study II on a self-administered questionnaire accompanied by a color photo booklet of all OC preparations ever marketed in the US. To evaluate the quality of this information, we compared the responses of a randomly selected sample of 215 participants with their data from a subsequent, detailed telephone interview using a structured life events calendar. Agreement for a history of ever having used OC was high between the two methods (exact agreement 99%). Reported durations of use were equivalent (mean duration 42.7 months by telephone interview and 44.6 months by questionnaire). The Spearman correlation for duration of use calculated from the two methods was 0.94 (p < 0.0001). For a subset of women for whom we were able to obtain OC prescription records, the medical record confirmed the use of an identical or equivalent brand in 75% of intervals of reported use. Acceptably valid OC histories were obtained with a self-administered questionnaire.

Adult↗

Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.

OBJECTIVE: To quantify the incidence of uterine leiomyoma confirmed by hysterectomy, ultrasound, or pelvic examination according to age and race among premenopausal women. METHODS: From September 1989 through May 1993, 95,061 premenopausal nurses age 25-44 with intact uteri and no history of uterine leiomyoma were followed to determine incidence rates of uterine leiomyoma. The self-reported diagnosis was confirmed in 93% of the medical records obtained for a sample of cases. Using pooled logistic regression, we estimated relative risks (RRs) of uterine leiomyoma according to race and examined whether adjustment for other potential risk factors could explain the variation in the race-specific rates. RESULTS: During 327,065 woman-years, 4181 new cases of uterine leiomyoma were reported. The incidence rates increased with age, and the age-standardized rates of ultrasound- or hysterectomy-confirmed diagnoses per 1000 woman-years were 8.9 among white women and 30.6 among black women. After further adjustment for marital status, body mass index, age at first birth, years since last birth, history of infertility, age at first oral contraceptive use, and current alcohol consumption, the rates among black women were significantly greater for diagnoses confirmed by ultrasound or hysterectomy (RR 3.25; 95% confidence interval [CI] 2.71, 3.88) and by hysterectomy (RR 1.82; 95% CI 1.17, 2.82) compared with rates among white women. We observed similar RRs when the cohort was restricted to participants who reported undergoing a screening physical examination within the 2 years before baseline. CONCLUSION: A higher prevalence of known risk factors did not explain the excess rate of uterine leiomyoma among premenopausal black women.

Adult↗

A prospective study of oral contraceptive use and risk of breast cancer (Nurses' Health Study, United States).

Results of previous epidemiologic studies have provided reassurance that there is little, if any, increase in risk of breast cancer with oral contraceptive (OC) use in general. However, in several studies, an increased risk of breast cancer has been observed in two subgroups, young women who used OCs for extended durations and in women who used OCs prior to a first-term pregnancy. We evaluated these relationships using data from the ongoing Nurses' Health Study cohort (United States). We documented 3,383 cases of breast cancer from 1976 to 1992 among 1.6 million person-years of follow-up. We observed no overall relationship between duration of OC use and breast cancer risk, even among women who reported using OCs for 10 or more years (multivariate relative risk [RR] = 1.11, 95 percent confidence interval [CI] = 0.94-1.32). Among women less than 45 years of age, the multivariate RR for using OCs for 10 or more years was 1.07 (CI = 0.70-1.65) compared with never-users. The risk associated with five or more years of OC use prior to a first full-term pregnancy compared with never-use was 0.96 (CI = 0.65-1.43). Among women less than 45 years of age, we observed no evidence of an increased risk with OC use before a first full-term pregnancy (use for five or more years: RR = 0.57, CI = 0.24-1.31). Because of the age distribution of our cohort, we were unable to evaluate these relationships among women less than 40 years of age. Our study provides considerable evidence that long-term past OC use, either overall or prior to a first full-term pregnancy, does not result in any appreciable increase in breast cancer risk in women over 40 years of age.

Adult↗

Physical activity and risk of colon cancer: the Physicians' Health Study (United States).

Previous studies indicate that physical activity is related inversely to colon cancer risk. However, details regarding that association--whether a dose-response relation exists, whether the relation differs between non-obese and obese persons, the effect of long-term physical activity--are unclear. We examined these issues in the Physicians' Health Study (United States). Physical activity was assessed at baseline among 21,807 men, aged 40 to 84 years, and again 36 months later. Men were followed for an average of 10.9 years (from baseline) during which 217 developed colon cancer. After adjusting for potential confounders (including age, obesity, and alcohol intake), the relative risks for colon cancer associated with vigorous exercise in times per week (< 1, 1, 2-4, 5+, at baseline) were 1.0 (referent); 1.1 (95% confidence interval [CI] = 0.7-1.7); 1.2 (CI = 0.8-1.6); and 1.1 (CI = 0.7-1.6), respectively; P trend = 0.6. Physical activity was not associated significantly with colon cancer risk either among non-obese or obese men. When we used physical activity assessments at baseline as well as at 36 months, physical activity again was unrelated to colon cancer risk. These data do not support the hypothesis that physical activity reduces the risk of colon cancer. Plausible alternate explanations for the null finding include misclassification of physical activity and the potential for increased surveillance for colon cancer ('screening effect') among those physically active.

Adult↗

The Nurses' Health Study: 20-year contribution to the understanding of health among women.

The Nurses' Health Study was designed as a prospective follow-up study to examine relations between contraception and breast cancer. With follow-up questionnaires mailed every 2 years, investigators have added extensive details of lifestyle practices. The study, currently in its 20th year, has maintained high follow-up with > 90% of participants responding to each of the follow-up cycles since 1988. The relations between use of hormones, diet, exercise, and other lifestyle practices have been related to the development of a wide range of chronic illnesses among women. This review describes the methods used to follow up the study participants and summarizes the major findings that have been described over the first 20 years of the study. We highlight additional areas added to the study in recent years to address emerging issues in women's health. Special emphasis is placed on the recent findings from the study, including relations between weight gain and heart disease, diabetes, and mortality, the lack of relation between calcium and osteoporotic fractures, and the positive relation between postmenopausal use of hormones and risk of breast cancer.

Adult↗

Obesity and mortality: a review of the epidemiologic data.

At least one-third of Americans are obese, as defined by body mass indexes corresponding to body weight > or = 120% of ideal body weight, and this figure is rising steadily. Women and nonwhites have particularly high rates of obesity. Obesity greatly increases risks for many serious and morbid conditions, including diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, and some cancers. Obesity is clearly associated with increased risk for mortality, but there has been controversy regarding optimal weight with respect to mortality risk. We review the literature concerning obesity and mortality, with reference to body fat distribution and weight gain, and consider potential effects of sex, age, and race on this relation. We conclude that when appropriate adjustments are made for effects of smoking and underlying disease, optimal weights are below average in both men and women; this appears to be true throughout the adult life span. Central obesity, most commonly approximated by the waist-to-hip ratio, may be particularly detrimental, although this requires further study. Weight gain in adulthood is also associated with increased mortality. These observations support public health measures to reduce obesity and weight gain, including recent recommendations to limit weight gain in the adult years to 4.5 kg (10 lb).

Adolescent↗

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.

Acetylation↗

A prospective study of oral contraceptives and NIDDM among U.S. women.

OBJECTIVE: To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires. RESULTS: During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9-3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8-1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6-2.8), and for past users, RR = 0.9 (95% CI, 0.6-1.4), suggesting that increased surveillance may explain at least part of any excess risk. CONCLUSIONS: In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.

Adult↗

Postmenopausal hormone replacement therapy and cardiovascular disease.

Cardiovascular disease is the leading cause of mortality in postmenopausal women in developed countries. A possible cardioprotective role of hormone replacement therapy (HRT) is suggested by epidemiologic studies of HRT and reduced risk of coronary heart disease, as well as by randomized trials of HRT and lipid subfractions. Estrogen has beneficial effects on the lipid profile, raising high-density lipoprotein cholesterol levels and reducing low-density lipoprotein cholesterol levels each by approximately 10%. Other possible biologic mechanisms include beneficial effects on vascular function, oxidative status, endothelial-dependent vasodilation, intimal hyperplasia and insulin sensitivity. Estrogen's net effects on coagulation and fibrinolysis are less clear. Estrogen replacement therapy is associated with decreased atherosclerosis in several animal models. However, most of the available data on HRT derive from observational studies or small randomized trials assessing biologic intermediates rather than clinical events. Further research, including large-scale randomized clinical trials, are required to evaluate definitively the role of estrogen replacement therapy, especially given uncertainties about the effects of combined estrogen-progestin therapy and the balance of benefits and risk of this common intervention in postmenopausal women.

Cardiovascular Diseases↗

Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.

A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval, 0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years; 51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who were diagnosed with breast cancer following blood collection and prior to June of 1992 and compared with age-matched controls, the GSTM1 deletion was not associated with an elevation in risk (relative risk, 1.08; 95% confidence interval, 0.74-1.57). No significant interaction with cigarette smoking was evident. Thus, there was no significant increase in risk of incident breast cancer associated with the GSTM1 null genotype; however, the gene deletion polymorphism appeared to confer improved survival. These data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival. Further studies are required to determine whether this polymorphism is associated with improved breast cancer prognosis.

Adult↗

Birthweight as a risk factor for breast cancer.

BACKGROUND: The mammary gland is largely undifferentiated before birth and may be particularly susceptible to intrauterine influences that could increase the risk of cancer through acceleration of cell proliferation or other pregnancy-related processes. Studies of migrant populations, animal data, and limited epidemiological evidence suggest that breast cancer may originate in utero. In a nested case-control study we assessed whether birthweight and other perinatal factors are associated with risk of breast cancer. METHODS: This case-control study was nested within the cohorts of the two Nurses' Health Studies. We used self-administered questionnaires to obtain information from the mothers of 582 nurses with invasive breast cancer and the mothers of 1569 nurses who did not have breast cancer (controls). Information on risk factors for breast cancer during adulthood were obtained from the nurses; multiple logistic regression analysis adjusted for these risk factors. FINDINGS: Birthweight was a significant predictor of breast-cancer risk. With women who weighed 4000 g or more at birth as the reference category, the adjusted odds ratios for breast cancer were 0.86 (95% CI 0.59-1.25) for birthweights of 3500-3999 g, 0.68 (0.48-0.97) for birthweights of 3000-3499 g, 0.66 (0.45-0.98) for birthweights of 2500-2999 g, and 0.55 (0.33-0.93) for birthweights below 2500 g (p for trend 0.004). Prematurity was not significantly associated with risk of breast cancer. INTERPRETATION: Birthweight is significantly associated with breast-cancer risk, which suggests that intrauterine factors or processes affect the risk of breast cancer in the offspring. High concentrations of pregnancy oestrogens may have an important role in breast carcinogenesis, but other pregnancy hormones or intrauterine factors may also be involved.

Adult↗

Prospective study of exogenous hormones and risk of pulmonary embolism in women.

BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.

Adult↗

A prospective study of cigarette smoking and risk of age-related macular degeneration in men.

OBJECTIVE: To examine the association between cigarette smoking and the incidence of age-related macular degeneration (AMD) in men. DESIGN: Prospective cohort study with average person-years of follow-up for AMD of 12.2 years. PARTICIPANTS: A total of 21 157 US male physicians participating in the Physicians' Health Study who did not have a diagnosis of AMD at baseline, were followed for at least 7 years, and had known levels of baseline smoking. Based on information reported at baseline, 11% were current smokers, 39% were past smokers, and 50% were never smokers. MAIN OUTCOME MEASURE: Incident AMD, defined as a self-report that was confirmed by medical record, review, first diagnosed after randomization, and responsible for vision loss to 20/30 or worse. RESULTS: A total of 268 incident cases of AMD with vision loss were confirmed. In multivariate analysis, current smokers of 20 or more cigarettes per day, compared with never smokers, had an increased risk of AMD (relative risk [RR], 2.46; 95% confidence interval [CI], 1.60-3.79). Past smokers had a modest elevation in risk of AMD (RR, 1.30; 95% CI, 0.99-1.70). For current smokers of fewer than 20 cigarettes per day, there was a nonsignificant 26% increased risk of AMD (RR, 1.26; 95% CI, 0.61-2.59). CONCLUSIONS: These prospective data provide support for the hypothesis that cigarette smoking increases the risk of developing AMD.

Adult↗