Showing papers by "Frank E. Speizer published in 1997"
TL;DR: The relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976, was examined.
Abstract: Background Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. Methods We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. Results After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; ...
1,076 citations
TL;DR: Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones.
Abstract: Context. —Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease. Objective. —To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality. Design. —Cohort study. Setting. —A cohort of 95256 US female nurses aged 30 to 55 years who were followed up for 16 years. Main Outcome Meausure. —Incident and fatal breast cancer. Results. —During 1 203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m2vs ≤20 kg/m2; 95% confidence interval, 1.09-2.32;Pfor trend Conclusions. —Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones.
853 citations
TL;DR: Among 43,581 women enrolled in the Nurses' Health Study who in 1986 provided waist, hip, and weight information and who were initially free from diabetes and other major chronic diseases, NIDDM incidence was followed from 1986 to 1994.
Abstract: Obesity is an established risk factor for non-insulin-dependent diabetes mellitus (NIDDM). Anthropometric measures of overall and central obesity as predictors of NIDDM risk have not been as well studied, especially in women. Among 43,581 women enrolled in the Nurses' Health Study who in 1986 provided waist, hip, and weight information and who were initially free from diabetes and other major chronic diseases, NIDDM incidence was followed from 1986 to 1994. After adjustment for age, family history of diabetes, smoking, exercise, and several dietary factors, the relative risk of NIDDM for the 90th percentile of body mass index (BMI) (weight (kg)/height (m)2) (BMI = 29.9) versus the 10th percentile (BMI = 20.1) was 11.2 (95% confidence interval (CI) 7.9-15.9). Controlling for BMI and other potentially confounding factors, the relative risk for the 90th percentile of waist: hip ratio (WHR) (WHR = 0.86) versus the 10th percentile (WHR = 0.70) was 3.1 (95% CI 2.3-4.1), and the relative risk for the 90th percentile of waist circumference (36.2 inches or 92 cm) versus the 10th percentile (26.2 inches or 67 cm) was 5.1 (95% CI 2.9-8.9). BMI, WHR, and waist circumference are powerful independent predictors of NIDDM in US women. Measurement of BMI and waist circumference (with or without hip circumference) are potentially useful tools for clinicians in counseling patients regarding NIDDM risk and risk reduction.
844 citations
TL;DR: Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk.
Abstract: Context. —Gestational diabetes mellitus (GDM) affects 3% to 5% of pregnancies. Knowledge of risk factors for GDM is needed to identify possible preventive strategies. Objective. —To assess whether recognized determinants of non-insulindependent diabetes mellitus also may be markers for increased risk of GDM. Design. —Prospective cohort study. Setting. —The Nurses' Health Study II, which involves female US nurses aged 25 to 42 years at entry. Participants. —The analyses included 14613 women without previous GDM or other known diabetes who reported a singleton pregnancy between 1990 and 1994. Of these women, 722 (4.9%) reported a new diagnosis of GDM. Main Outcome Measure: Self-report of GDM, validated by medical record review in a subset. Results. —multivariate analyses including age, pregravid body mass index (BMI), and other GDM risk factors, the risk for GDM increased significantly with increasing maternal age ( P for trend, 2 and 2.90 (95% CI, 2.15-3.91) for BMI of 30 kg/m 2 or more (vs BMI of 2 ) Risk for GDM increased with greater weight gain in early adulthood, and it also increased among nonwhite women. Pregravid current smokers had a relative risk for GDM of 1.43 (95% CI, 1.14-1.80), and pregravid vigorous exercise was associated with a nonsignificant reduction in GDM risk. Conclusions. —Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk. These observations may facilitate the identification of women at particular risk for GDM and suggest potential strategies for reducing this risk even before a woman becomes pregnant, such as avoiding substantial weight gain and smoking.
733 citations
TL;DR: A 12-year prospective analysis among 91 731 women who were participating in the Nurses' Health Study and had no history of kidney stones at study entry found that high intake of dietary calcium was associated with a decreased risk for stone formation.
Abstract: Background: Calcium intake is believed to play an important role in the formation of kidney stones, but data on the risk factors for stone formation in women are limited. Objective: To examine the ...
661 citations
TL;DR: Obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke, according to prospective data from the Nurses' Health Study, which examined the associations of body mass index (BMI) and weight change with risk of stroke in women.
Abstract: Objective. —To examine the associations of body mass index (BMI) and weight change with risk of stroke in women. Setting and Design. —Prospective cohort study among US female registered nurses participating in the Nurses' Health Study. Participants. —A total of 116 759 women aged 30 to 55 years in 1976 who were free from diagnosed coronary heart disease, stroke, and cancer. Main Outcome Measure. —Incidence of ischemic stroke, hemorrhagic stroke (subarachnoid or intraparenchymal hemorrhage), and total stroke. Results. —During 16 years of follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic strokes) were documented. In multivariate analyses adjusted for age, smoking, postmenopausal hormone use, and menopausal status, women with increased BMI (≥27 kg/m 2 ) had significantly increased risk of ischemic stroke, with relative risks (RRs) of 1.75 (95% confidence interval [CI], 1.17-2.59) for BMI of 27 to 28.9 kg/m 2 ; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m 2 ; and 2.37 (95% CI, 1.60-3.50) for BMI of 32 kg/m 2 or more ( P for trend 2 . For hemorrhagic stroke there was a nonsignificant inverse relation between obesity and hemorrhagic stroke, with the highest risk among women in the leanest BMI category ( P for trend=.20). For total stroke the RRs were somewhat attenuated compared with those for ischemic stroke but remained elevated for women with higher BMI ( P for trend P for trend P for trend=.20), a direct relationship was observed between weight gain and total stroke risk ( P for trend Conclusions. —These prospective data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke. The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population.
617 citations
TL;DR: It is indicated that obesity, cigarette smoking, and hypertension are associated with increased risk of pulmonary embolism in women and control of these risk factors will decrease risks of pulmonaryembolism as well as coronary heart disease.
Abstract: Objective. —To investigate risk factors for pulmonary embolism in women. Design. —Prospective study based on biennial, mailed questionnaires. Setting. —Nurses' Health Study with 16 years of follow-up from 1976 to 1992. Patients. —A group of 112 822 women aged 30 to 55 years in 1976, free from diagnosed cardiovascular disease or cancer at baseline. Overall, there were 1 619770 person-years of follow-up. Measurements. —Based on self-report and medical records, we documented 280 cases of pulmonary embolism, of which 125 were primary (no identified antecedent cancer, trauma, surgery, or immobilization). Information on height, weight, cigarette smoking, hypertension, diabetes, and hypercholesterolemia was collected by questionnaire. Results. —In multivariate analysis, obesity, cigarette smoking, and hypertension were independent predictors of pulmonary embolism. Specifically, obese women (body mass index ≥ 29.0 kg/m2) had an increased risk of primary pulmonary embolism (multivariate relative risk=2.9; 95% confidence interval [CI], 1.5-5.4). Heavy cigarette smokers also had an increased risk of primary pulmonary embolism. The relative risk (RR) of primary pulmonary embolism was 1.9 (95% CI, 0.9-3.7) for women currently smoking 25 to 34 cigarettes per day and 3.3 (95% CI, 1.7-6.5) for those smoking 35 cigarettes or more daily as compared with never smokers. Hypertension, even after adjustment for body mass index, was also associated with an increased risk of primary pulmonary embolism (RR=1.9; 95% CI, 1.2-2.8). High serum cholesterol levels (RR=1.1; 95% CI, 0.62-1.8) and diabetes (RR=0.7; 95% CI, 0.3-1.9) did not appear to be related to primary pulmonary embolism. Conclusion. —These prospective data indicate that obesity, cigarette smoking, and hypertension are associated with increased risk of pulmonary embolism in women. Control of these risk factors will decrease risks of pulmonary embolism as well as coronary heart disease.
568 citations
Journal Article•
TL;DR: The risk of primary PE was uncommon in this cohort and was increased by current though not past use of postmenopausal hormones or OCs, consistent irrespective of cigarette-smoking status.
Abstract: 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.
428 citations
TL;DR: The hypothesis that exposure to DDT and PCBs increases the risk of breast cancer is rejected, as the data do not support the hypothesis.
Abstract: Background Exposure to “environmental estrogens” such as organochlorines in pesticides and industrial chemicals has been proposed as a cause of increasing rates of breast cancer. Several studies have reported higher blood levels of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) in patients with breast cancer than in controls. Methods We measured plasma levels of DDE and PCBs prospectively among 240 women who gave a blood sample in 1989 or 1990 and who were subsequently given a diagnosis of breast cancer before June 1, 1992. We compared these levels with those measured in matched control women in whom breast cancer did not develop. Data on DDE were available for 236 pairs, and data on PCBs were available for 230 pairs. Results The median level of DDE was lower among case patients than among controls (4.71 vs. 5.35 parts per billion, P = 0.14), as was the median level of PCBs (4.49 vs. 4.68 parts per billion, P = 0.72). The multivariate relative risk of breast cancer...
374 citations
TL;DR: Regular exposure to passive smoking at home or work increases the risk of CHD among nonsmoking women, and there was no relation apparent between duration of living with a smoker and risk ofCHD.
Abstract: Background Several epidemiological studies have suggested an association of passive smoking with coronary heart disease (CHD). However, few studies have taken account of exposure to passive smoking...
214 citations
TL;DR: A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated, and data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant Size at birth.
Abstract: Background Most studies of the reproductive consequences of cigarette smoking base exposure on self-reported smoking habits This study examines the relationship of birth outcomes to the timing and intensity of maternal active and passive smoking estimated both from self-reports and from cotinine concentration in maternal urine during early, middle, and late gestation Method This cohort study included 740 white and Hispanic women who obtained antenatal care at the East Boston Neighborhood Health Center between 1986 and 1992 At each antenatal visit, information on maternal active and passive smoking was obtained by a detailed questionnaire, and by measurement of urine cotinine concentrations Infant birth outcomes were obtained from hospital records Multiple linear regression was used to evaluate antenatal smoking variables on birth outcomes, with adjustment for maternal demographic characteristics, reproductive history, alcohol use, maternal weight and height, and infant gender Results The percentage of mothers who ever smoked cigarettes during pregnancy was 555% for white and 102% for Hispanic women A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated However, the relationship was less clear between maternal self-reported smoking status and these outcomes For the entire gestation, a 1000 ng increase in mean urine cotinine concentration was associated with a 59 +/- 9 g reduction in birthweight, a 025 +/- 005 cm reduction in length, and a 012 +/- 003 cm reduction in head circumference, respectively For maternal passive smoking, the much smaller magnitude of effect precludes firm conclusions Conclusions These data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant size at birth
TL;DR: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.
Abstract: Background Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. Methods We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. Results After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; ...
TL;DR: Past use of OCs was associated with a slightly increased risk of developing SLE, and the decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.
Abstract: The aim of this study was to examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE). A prospective cohort study of 121645 women who were followed up every 2 years between 1976 and 1990 was conducted as part of the Nurses Health Study. Women were classified as never users or past users of OCs based on self-report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (>or= 4 ACR criteria) 2) >or= 4 ACR criteria and any physicians diagnosis 3) >or= 4 ACR criteria and diagnosis by an ACR-certified rheumatologist 4) >or= 3 ACR criteria or 5) diagnosis by a physician even if the patient did not meet the ACR criteria. Compared with never users of OCs and after adjusting for age and ever use of postmenopausal hormones the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (>or= 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58) the relative risk for past users compared with never users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE. Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized but the small absolute risk observed for the development of SLE in White women should not be a dominant factor in the decision. (authors)
TL;DR: In this paper, the authors examined the relation between cardiovascular disease and postmenopausal hormone therapy during up to 16 years of follow-up in 59,337 women from the Nurses' Health Study, who were 30 to 55 years of age at base line.
TL;DR: Little evidence of an association between NAT2 genotype and breast cancer is observed in this prospective study of mainly Caucasian US women, and cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.
Abstract: 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.
TL;DR: The effect of total body fat as a percentage of weight (TBF%) on ventilatory function in a nationally representative sample of Australian school children aged 9, 12, and 15 years is examined.
Abstract: Childhood obesity is associated with a range of adverse consequences, and the prevalence is increasing in developed nations. Most of the literature on obesity and ventilatory function in children concerns samples selected for gross obesity with relatively little detail available from random population samples. This report examines the effect of total body fat as a percentage of weight (TBF%) on ventilatory function in a nationally representative sample of 2,464 Australian school children aged 9, 12, and 15 years. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were used as measures of ventilatory function. TBF% was estimated from skinfold thickness measurements. Ventilatory function was adjusted (for height and then for both height and weight) using linear regression on a logarithmic scale. Adjustment was performed within separate strata of age and gender. Analysis of covariance was used for hypothesis testing. Height-adjusted FVC and FEV1 values increased significantly with increasing weight within each age and gender group and for all subjects combined (P < 0.0001). The effect of TBF% independent of lean tissue was examined using FVC and FEV1 values adjusted for both height and weight, because body weight measures both lean and fat mass. Adjusted FVC and FEV1 values decreased significantly with increasing TBF% within each age and gender group and for all subjects combined (P < 0.0001). Ventilatory function decreased with increasing proportions of body fat. This is consistent with previous findings on lean tissue mass and ventilatory function. Although the magnitude of the effect was relatively small in clinical terms, from a public health perspective our findings indicate yet another adverse consequence of childhood obesity.
Journal Article•
TL;DR: Examining incident cases of colorectal cancer that occurred during 1,012,280 person-years of follow-up between 1980 and 1992 in the Nurses' Health Study suggests that a later age of menarche and use of oral contraceptives may reduce risk of colorescopy cancer, whereas women with aLater age at first pregnancy may have a higher risk.
Abstract: To explore the roles of reproductive factors and oral contraceptive use in the etiology of colorectal cancer, we examined incident cases of colorectal cancer (n = 501) that occurred during 1,012,280 person-years of follow-up between 1980 and 1992 in the Nurses' Health Study. The women completed mailed, self-administered questionnaires every 2 years to update information on the risk factors and major medical events. In multivariate analysis, the relative risk (RR) of colorectal cancer among women who experienced menarche at age 14 or older was 0.83 (95% confidence interval (CI) = 0.64-1.08) compared with women who had menarche at age 13; women whose menarche occurred under age 12 were at higher risk (RR = 1.22; 95% CI = 0.96-1.55, P for trend = 0.01). Compared with women whose first pregnancy was before age 24, the risk for colorectal cancer was significantly increased among women whose first pregnancy was at age 30 or older (RR = 1.57; 95% CI = 1.15-2.14; P for trend = 0.02). No important associations were seen for parity or age at menopause. Women who used oral contraceptives for 96 months or longer had a 40% lower risk of developing colorectal cancer (RR = 0.60; 95% CI = 0.40-0.89; P for trend = 0.02) compared with women who never used oral contraceptives. These prospective data suggest that a later age of menarche and use of oral contraceptives may reduce risk of colorectal cancer, whereas women with a later age at first pregnancy may have a higher risk.
TL;DR: Histories of oral contraceptive 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.
TL;DR: In this paper, a nested case-control study was conducted to assess whether birthweight and other perinatal factors are associated with risk of breast cancer, and the authors found that birthweight was a significant predictor of breast-cancer risk.
Abstract: Summary 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.
TL;DR: In this paper, the authors found 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).
Abstract: 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.
01 Jan 1997
TL;DR: This 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.
Abstract: 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. Cancer Causes and Control 1997, 8, 65-72
TL;DR: This article found no clear evidence in any subgroups of a major relation between total energy-adjusted fat intake and breast cancer risk, with fat intake being associated nonsignificantly positively with risk among women with a previous history of benign breast disease; no other significant interactions were observed.
Abstract: To assess more precisely the relative risks associated with established risk factors for breast cancer, and whether the association between dietary fat and breast cancer risk varies according to levels of these risk factors, we pooled primary data from six prospective studies in North America and Western Europe in which individual estimates of dietary fat intake had been obtained by validated food-frequency questionnaires. Based on information from 322,647 women among whom 4,827 cases occurred during follow-up: the multivariate-adjusted risk of late menarche (age 15 years or more compared with under 12) was 0.72 (95 percent confidence interval [CI] = 0.62-0.82); of being postmenopausal was 0.82 (CI = 0.69-0.97); of high parity (three or more births compared with none) was 0.72 (CI = 0.61-0.86); of late age at first birth (over 30 years of age compared with 20 or under) was 1.46 (CI = 1.22-1.75); of benign breast disease was 1.53 (CI = 1.41-1.65); of maternal history of breast cancer was 1.38 (CI = 1.14-1.67); and history of a sister with breast cancer was 1.47 (CI = 1.27-1.70). Greater duration of schooling (more than high-school graduation compared with less than high-school graduation) was associated significantly with higher risk in age-adjusted analyses, but was attenuated after controlling for other risk factors. Total fat intake (adjusted for energy consumption) was not associated significantly with breast cancer risk in any strata of these non-dietary risk factors. We observed a marginally significant interaction between total fat intake and risk of breast cancer according to history of benign breast disease, with fat intake being associated nonsignificantly positively with risk among women with a previous history of benign breast disease; no other significant interactions were observed. Risks for reproductive factors were similar to those observed in case-control studies; relative risks for family history of breast cancer were lower. We found no clear evidence in any subgroups of a major relation between total energy-adjusted fat intake and breast cancer risk.
TL;DR: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California and adjustment for differences in the distribution of established risk factors explained some of the excess in California.
Abstract: Background: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. Methods: The Nurses' Health Study cohort was established in 1976 when 121700 female nurses aged 30-55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1794565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariate-adjusted analysis), comparing California, the Northeast, and the Midwest with the South. Results: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05-1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00-1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. Conclusions: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California.
Journal Article•
TL;DR: The data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival, and the GSTM1 deletion appeared to confer improved survival.
Abstract: 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.
TL;DR: For example, the authors found that 30-50% increases in the risk of lung cancer in relation to approximately a doubling of respirable particle exposure, suggesting that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the US, based largely on the results of animal experimentation, may be too low.
Abstract: Epidemiologic studies over the last 40 years have observed that general ambient air pollution, chiefly due to the by-products of the incomplete combustion of fossil fuels, is associated with small relative increases in lung cancer. The evidence derives from studies of lung cancer trends, studies of occupational groups, comparisons of urban and rural populations, and case-control and cohort studies using diverse exposure metrics. Recent prospective cohort studies observed 30-50% increases in the risk of lung cancer in relation to approximately a doubling of respirable particle exposure. While these data reflect the effects of exposures in past decades, and despite some progress in reducing air pollution, large numbers of people in the US continue to be exposed to pollutant mixtures containing known or suspected carcinogens. These observations suggest that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the US, based largely on the results of animal experimentation, may be too low. It is important that better epidemiologic research be conducted to allow improved estimates of lung cancer risk from air pollution in the general population. The development and application of new epidemiologic methods, particularly the improved characterization of population-wide exposure to mixtures of air pollutants and the improved design of ecologic studies, could improve our ability to measure accurately the magnitude of excess cancer related to air pollution.
Journal Article•
TL;DR: Observations suggest that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the US, based largely on the results of animal experimentation, may be too low.
Abstract: Epidemiologic studies over the last 40 years have observed that general ambient air pollution, chiefly due to the by-products of the incomplete combustion of fossil fuels, is associated with small relative increases in lung cancer. The evidence derives from studies of lung cancer trends, studies of occupational groups, comparisons of urban and rural populations, and case-control and cohort studies using diverse exposure metrics. Recent prospective cohort studies observed 30-50% increases in the risk of lung cancer in relation to approximately a doubling of respirable particle exposure. While these data reflect the effects of exposures in past decades, and despite some progress in reducing air pollution, large numbers of people in the US continue to be exposed to pollutant mixtures containing known or suspected carcinogens. These observations suggest that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the US, based largely on the results of animal experimentation, may be too low. It is important that better epidemiologic research be conducted to allow improved estimates of lung cancer risk from air pollution in the general population. The development and application of new epidemiologic methods, particularly the improved characterization of population-wide exposure to mixtures of air pollutants and the improved design of ecologic studies, could improve our ability to measure accurately the magnitude of excess cancer related to air pollution.
TL;DR: In this article, the authors examined the relation between cardiovascular disease and postmenopausal hormone therapy during up to 16 years of follow-up in 59,337 women from the Nurses' Health Study, who were 30 to 55 years of age at base line.
Abstract: Background Estrogen therapy in postmenopausal women has been associated with a decreased risk of heart disease. There is little information, however, about the effect of combined estrogen and progestin therapy on the risk of cardiovascular disease. Methods We examined the relation between cardiovascular disease and postmenopausal hormone therapy during up to 16 years of follow-up in 59,337 women from the Nurses' Health Study, who were 30 to 55 years of age at base line. Information on hormone use was ascertained with biennial questionnaires. From 1976 to 1992, we documented 770 cases of myocardial infarction or death from coronary disease in this group and 572 strokes. Proportional-hazards models were used to calculate relative risks and 95 percent confidence intervals, adjusted for confounding variables. Results We observed a marked decrease in the risk of major coronary heart disease among women who took estrogen with progestin, as compared with the risk among women who did not use hormones (multivariat...