Showing papers by "Frank E. Speizer published in 1998"

Alcohol and breast cancer in women: a pooled analysis of cohort studies.

Abstract: Objective. - To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. Data Sources. - We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322 647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. Data Extraction. - Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. Data Synthesis. - For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate- adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. Conclusions. - Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.

Abstract: Background: High intake of folate may reduce risk for colon cancer, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood. Obje...

Body Weight, Weight Change, and Risk for Hypertension in Women

Abstract: Background: Obesity increases the risk for hypertension, but the effects of modest long-term weight changes have not been precisely quantified. Objective: To investigate body mass index (BMI) and w...

Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women.

Abstract: ate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06‐3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05‐3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23‐ 4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11‐4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy. Conclusion: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer. [J Natl Cancer Inst 1998;90: 1292‐9]

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study

Abstract: Objective: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses9 Health Study. Design: Prospective cohort study. Setting: Nurses9 Health Study. Subjects: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. Main outcome measures: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. Results: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking, use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. Conclusions: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.

Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease: Risk to relatives for airflow obstruction and chronic bronchitis

Abstract: Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.

Body size and risk of kidney stones

Abstract: A variety of factors influence the formation of calcium oxalate kidney stones, including gender, diet, and urinary excretion of calcium, oxalate, and uric acid. Several of these factors may be related to body size. Because men on average have a larger body size and a threefold higher lifetime risk of stone formation than women, body size may be an important risk factor for calcium oxalate stone formation. The association between body size (height, weight, and body mass index) and the risk of kidney stone formation was studied in two large cohorts: the Nurses' Health Study (NHS; n = 89,376 women) and the Health Professionals Follow-up Study (HPFS; n = 51,529 men). Information on body size, kidney stone formation, and other exposures of interest was obtained by mailed questionnaires. A total of 1078 incident cases of kidney stones in NHS during 14 yr of follow-up and a total of 956 cases in HPFS during 8 yr of follow-up were confirmed. In both cohorts, the prevalence of a stone disease history and the incidence of stone disease were directly associated with weight and body mass index. However, the magnitude of the associations was consistently greater among women. Specifically, the age-adjusted prevalence odds ratio for women with body mass index > or = 32 kg/m2 compared with 21 to 22.9 kg/m2 was 1.76 (95% confidence interval, 1.50 to 2.07), but 1.38 (95% confidence interval, 1.16 to 1.65) for the same comparison in men. For incident stone formation, the multivariate relative risks for the similar comparisons were 1.89 (1.51 to 2.36) for women and 1.19 (0.83 to 1.70) in men. Height was inversely associated with the prevalence of stone disease but was not associated with incident stone formation. These results suggest that body size is associated with the risk of stone formation and that the magnitude of risk varies by gender. Additional studies are necessary to determine whether a reduction in body weight decreases the risk of stone formation, particularly in women.

Beverage Use and Risk for Kidney Stones in Women

Abstract: Background: An increase in fluid intake is routinely recommended for patients who have had kidney stones to decrease the likelihood of recurrence. However, data on the effect of particular beverage...

Cigarette Smoking, Cytochrome P450 1A1 Polymorphisms, and Breast Cancer Risk in the Nurses' Health Study

Abstract: Environmental exposure to carcinogens may contribute to increasing breast cancer rates and geographic variation in breast cancer incidence in the United States. One class of chemicals that has received much attention are the polyaromatic hydrocarbons that are ubiquitous in the environment and occur in cigarette smoke. The cytochrome P450 1A1 ( CYP1A1 ) gene codes for an enzyme that contributes to aryl hydrocarbon hydroxylase activity, which is involved in the metabolism of polyaromatic hydrocarbons. Genotypic variants of CYP1A1 have been associated with increased aryl hydrocarbon hydroxylase activity, and some epidemiological studies suggest that women with the variant genotype(s) are at increased risk for breast cancer. We prospectively evaluated the associations between the CYP1A1 polymorphisms and breast cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case-control study nested within the Nurses' Health Study. We analyzed the T→C transition at nucleotide 6235 ( Msp I) and the A→G transition at nucleotide 4889 ( exon 7 ) in CYP1A1 by PCR-RFLP assays among 466 incident breast cancer cases and 466 matched controls. Relative risks (RRs) and 95% confidence intervals (CIs) were used to quantify the risk of breast cancer among subjects who had at least one variant allele relative to subjects who were homozygous for the wild-type allele, using conditional logistic regression. No overall increase in breast cancer risk with the variant CYP1A1 genotypes was apparent (RR MspI , 1.05; 95% CI, 0.74–1.50 and RR exon 7 , 0.88; 95% CI, 0.58–1.33). However, a suggestive increase in breast cancer risk was observed among women who had commenced smoking before the age of 18 and had the CYP1A1-Msp I variant genotype compared to nonsmokers who were homozygous wild type for the polymorphism (RR, 5.65; 95% CI, 1.50–21.3; percentage of all breast cancer cases attributable to this risk factor, 2.5%). A similar gene-environment association was observed for the exon 7 polymorphism (RR, 3.61; 95% CI, 1.11–11.7; percentage of all breast cancer cases attributable to this risk factor, 2.2%). These data are compatible with the hypothesis that cigarette smoking early in life is a modifiable cause of breast cancer in a subpopulation of genetically susceptible women. However, the proportion of breast cancer attributable to cigarette smoking at a young age among Caucasian women with the variant form of the CYP1A1 polymorphisms is low.

Lower levels of physical functioning are associated with higher body weight among middle-aged and older women

Abstract: OBJECTIVE: To compare levels of physical function, across levels of body mass index (BMI), among middle- to older-aged women. DESIGN: Cross-sectional study. Physical function, body weight and other covariates were measured in 1992. SUBJECTS: 56 510 women aged 45–71 y, free of cardiovascular disease and cancer, participating in the Nurses’ Health Study. MAIN OUTCOME MEASURES: The four physical function scores on the Medical Outcomes Study (MOS) Short Form-36 (SF36) Health Survey: physical functioning, vitality, bodily pain and role limitations. RESULTS: After adjusting for age, race, smoking status, menopausal status, physical activity and alcohol consumption, there was a significant dose-response gradient between increasing levels of BMI in 1992 and reduced function. For example, women with a BMI between 30–34.9 kg/m2 averaged: 9.0 point lower physical functioning score (95% Confidence interval (CI) −9.5, −8.5), 5.6 point lower vitality score (95% CI: −6.1, −5.1), and 7.0 point lower freedom from pain score (95% CI: −7.6, −6.4). These declines represent an approximate 10% loss of function compared to the reference category of women with BMIs ranging from 22.0–23.9 kg/m2. For the same BMI comparison, heavier women were at 66% increased risk of limitations in ability to work or perform other roles (RR=1.66; 95% odds ratio (OR) CI: 1.56, 1.76). These findings were replicated when the sample was restricted to women who had maintained their BMI over a ten year period. CONCLUSIONS: In addition to increasing risk of chronic health conditions, greater adiposity is associated with lower every day physical functioning, such as climbing stairs or other moderate activities, as well as lower feelings of well-being and greater burden of pain.

Menstrual Cycle Characteristics and History of Ovulatory Infertility in Relation to Breast Cancer Risk in a Large Cohort of US Women

Abstract: Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25-42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche > 13 years compared with age 39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18-0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer.

Effects of ozone and other pollutants on the pulmonary function of adult hikers

Abstract: This study evaluated the acute effects of ambient ozone (O3), fine particulate matter (PM2.5), and strong aerosol acidity on the pulmonary function of exercising adults. During the summers of 1991 and 1992, volunteers (18-64 years of age) were solicited from hikers on Mt. Washington, New Hampshire. Volunteer nonsmokers with complete covariates (n = 530) had pulmonary function measured before and after their hikes. We calculated each hiker's posthike percentage change in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), the ratio of these two (FEV1/FVC), forced expiratory flow between 25 and 75% of FVC(FEF25-75%), and peak expiratory flow rate (PEFR). Average O3 exposures ranged from 21 to 74 ppb. After adjustment for age,sex, smoking status (former versus never), history of asthma or wheeze, hours hiked, ambient temperature, and other covariates, there was a 2.6% decline in FEV1 [95% confidence interval (CI), 0.4-4.7; p = 0.02] and a 2.2% decline in FVC (CI, 0.8-3.5; p =0.003) for each 50 ppb increment in mean O3. There were consistent associations of decrements in both FVC (0.4% decline; CI,0.2-0.6, p = 0.001) and PEFR (0.8% decline; CI, 0.01-1.6; p = 0.05) with PM2.5 and of decrements in PEFR (0.4% decline; CI, 0.1-0.7; p = 0.02) with strong aerosol acidity across the interquartile range of these exposures. Hikers with asthma or a history of wheeze (n = 40) had fourfold greater responsiveness to ozone than others. With prolonged outdoor exercise, low-level exposures to O3, PM2.5, and strong aerosol acidity were associated with significant effects on pulmonary function among adults. Hikers with a history of asthma or wheeze had significantly greater air pollution-related changes in pulmonary function.

Exposure of young infants to environmental tobacco smoke: breast-feeding among smoking mothers.

Abstract: OBJECTIVES: This study examined the degree to which breast-feeding and cigarette smoking by mothers and smoking by other household members contribute to the exposure of infants to the products of tobacco smoke. METHODS: The subjects were 330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a longitudinal study of the pulmonary effects of prenatal and postnatal smoking. The main outcome measure was corrected urinary cotinine levels. RESULTS: Urinary cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers, urine cotinine levels were significantly increased in infants living in homes with other smokers; in this group there was no significant difference between bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room as the infant had only nonsignificant increases in cotinine levels compared with infants whose mothers restricted their smoking to other rooms. CON...

Predictors of dietary heterocyclic amine intake in three prospective cohorts

Abstract: Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids and creatinine. Although recognized as mutagenic, the etiological role of HCA in human cancer is unclear, due to the lack of information on the effect of typical food cooking methods on HCA concentrations and on variation in HCA exposure in populations. We estimated overall daily dietary HCA intake and variation in intake between individuals, using recent data on HCA concentrations in various meats prepared by cooking methods, temperatures, and times common in United States in the 1990s. Random samples of 250 participants from each of three large prospective cohorts were mailed a questionnaire to assess frequency of consumption, cooking method, and typical outside appearance of pan-fried, broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried, microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in composite samples by solid-phase extraction and high-performance liquid chromatography, were assigned to each food, cooking method, and doneness level. The dietary reports showed approximately 30-fold relative variation in 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6-phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA intake were compared (90th/10th percentile value). These reported variations in HCA exposure among participants in these three large cohorts indicates that estimation of HCA intake and determination of association with disease risk are feasible, if additional information on meat cooking methods is obtained.