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Biomedical subjects

Jo L Freudenheim

Publications and source records attributed to Jo L Freudenheim.

17 recordsLinked to original sources

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors.

BACKGROUND: Findings from previous studies regarding the association between the CYP17 genotype and breast cancer are inconsistent. We investigated the role of the MspAI genetic polymorphism in the 5' region of CYP17 on risk of breast cancer and as a modifier of reproductive risk factors. METHODS: Questionnaire and genotyping data were obtained from a population-based, case-control study of premenopausal (n = 182) and postmenopausal (n = 214) European-American Caucasian women in western New York. Cases and controls were frequency matched by age and by county of residence. Odds ratios and 95% confidence intervals were used to estimate relative risks. RESULTS: The CYP17 genotype was not associated with breast cancer risk; however, controls with the A2/A2 genotype (associated with higher estrogens) had earlier menarche and earlier first full-term pregnancy. Premenopausal women with A1/A1 genotypes, but not with A2 alleles, were at significantly decreased risk with late age at menarche (odds ratio = 0.37, 95% confidence interval = 0.14-0.99), and at increased risk with late age at first full-term pregnancy (odds ratio = 4.30, 95% confidence interval = 1.46-12.67) and with use of oral contraceptives (odds ratio = 3.24, 95% confidence interval = 1.08-9.73). Associations were weaker among postmenopausal women. CONCLUSION: These results suggest that the effects of factors that may alter breast cancer risk through a hormonal mechanism may be less important among premenopausal women with putative higher lifetime exposures to circulating estrogens related to the CYP17 A2 allele.

Adult↗

Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups.

Intakes of specific nutrients and food groups have been shown previously to be related to ovarian cancer risk, but no studies, to our knowledge, have emphasized the effect of phytochemical intakes on this cancer. We conducted a case-control study of diet and ovarian cancer in western New York involving 124 primary, histologically confirmed ovarian cancer cases and 696 population-based controls, frequency matched to cases on age and county of residence. Diet was assessed with a detailed food-frequency questionnaire. Nutrient and phytochemical intakes were calculated from published food composition data. The odds ratios (OR) and 95% CI for risk of ovarian cancer with each nutrient, phytochemical and food group were estimated with unconditional logistic regression adjusting for age, education, total months menstruating, difficulty becoming pregnant, oral contraceptive use, menopausal status and energy intake. Compared with women in the lowest quintile of intake, reduced risks were observed for women in the highest quintile of intake of dietary fiber (OR 0.43, 95% CI, 0.20-0.94), total carotenoids (OR 0.33, 95% CI, 0.16-0.68), stigmasterol (OR 0.42, 95% CI, 0.20-0.87), total lignans (OR 0.43, 95% CI, 0.21-0.85), vegetables (OR 0.47, 95% CI, 0.23-0.97) and poultry (OR 0.45, 95% CI, 0.22-0.92). These results support a protective effect on ovarian cancer of phytoestrogen intakes, and our results support the hypothesis that a plant-based diet may be important in reducing risks of hormone-related neoplasms.

Adult↗

Alcohol drinking patterns differentially affect central adiposity as measured by abdominal height in women and men.

Alcohol drinking in light-to-moderate amounts has been associated with reduced coronary heart disease (CHD) risk. However, there is evidence that the way people consume alcohol (drinking pattern) may affect risk. Central adiposity, a known CHD risk factor may be one mechanism in the pathway between alcohol consumption and CHD risk. Our study examined whether various drinking patterns differentially affect fat distribution, particularly abdominal fat in women and men. In a randomly selected population-based cohort (n = 2343), 35-79 y old, we assessed drinking pattern as reported for the past 30 d, including beverage type and amount, frequency of consumption, percentage of time drinking while eating and number of drinks consumed/drinking day. Central adiposity was determined using an abdominal caliper to measure supine height of the abdomen. Current drinkers tended to have smaller abdominal heights than nondrinkers (women, P < 0.0001; men, P = 0.0559). For drinking pattern, frequency was inversely associated, but drinking intensity (drinks/drinking day) was positively associated with central adiposity in women (P trend for frequency, 0.0007; intensity, 0.0010) and men (P trend for frequency, 0.0005; intensity, 0.0004), even when age, education, physical activity, smoking status and amount of alcohol (g) were included in the models. When frequency and intensity were considered together, daily drinkers of <1 drink/drinking day had the smallest mean abdominal height measures with the largest measures in less than weekly drinkers who consumed 4 or more drinks/drinking day. These results support the hypothesis that drinking pattern affects the distribution of body fat, an important CHD risk factor.

Abdomen↗

Positional accuracy of geocoded addresses in epidemiologic research.

BACKGROUND: Geographic information systems (GIS) offer powerful techniques for epidemiologists. Geocoding is an important step in the use of GIS in epidemiologic research, and the validity of epidemiologic studies using this methodology depends, in part, on the positional accuracy of the geocoding process. METHODS: We conducted a study comparing the validity of positions geocoded with a commercially available program to positions determined by Global Positioning System (GPS) satellite receivers. Addresses (N = 200) were randomly selected from a recently completed case-control study in Western New York State. We geocoded addresses using ArcView 3.2 on the GDT Dynamap/2000 U.S. Street database. In addition, we measured the longitude and latitude of these addresses with a GPS receiver. The distance between the locations obtained by these two methods was calculated for all addresses. RESULTS: The distance between the geocoded point and the GPS point was within 100 m for the majority of subject addresses (79%), with only a small proportion (3%) having a distance greater than 800 m. The overall median distance between GPS points and geocoded points was 38 m (90% confidence interval [CI] = 34-46). Distances were not different for cases and controls. Urban addresses (median = 32 m; CI = 28-37) were slightly more accurate than nonurban addresses (median = 52 m; CI = 44-61). CONCLUSIONS: This study indicates that the suitability of geocoding for epidemiologic research depends on the level of spatial resolution required to assess exposure. Although sources of error in positional accuracy for geocoded addresses exist, geocoding of addresses is, for the most part, very accurate.

Environmental Health↗

Relation between lung function and RBC distribution width in a population-based study.

STUDY OBJECTIVES: Pulmonary function is dependent not only on smoking, but also on nutritional status. Since an increased RBC distribution width (RDW) has been associated with nutritional deficiencies, we postulated that RDW has an inverse relation to pulmonary function. The purpose of this study was to test this hypothesis. DESIGN AND SETTING: A cross-sectional study was conducted of a random sample of the general population in western New York. PARTICIPANTS: A total of 1,616 subjects of both genders who were aged 35 to 79 years and were free of respiratory disease. INTERVENTIONS: None. MEASUREMENTS: Pulmonary function was assessed from FEV(1), FVC, height, body weight, total pack-years of smoking, smoking status, hemoglobin concentration, and hematologic indexes, eosinophil count, education, and blood levels of retinol, beta-cryptoxanthin, and vitamin E. RESULTS: We found a direct relation between RDW and the number of pack-years of smoking and smoking status, and an inverse relation between FEV(1) and FVC with RDW, even when potentially confounding variables such as smoking were taken into account. When the variability of FEV(1) due to smoking was used for comparison, an additional 27% of that variability in FEV(1) was explained by variations in antioxidant vitamin levels, and another 24% by RDW. CONCLUSIONS: The results confirmed our hypothesis that there is an inverse relation between RDW and pulmonary function, and raise the possibility that RDW may be a biomarker for as-yet unidentified nutrients that affect pulmonary function.

Adult↗

Beverage specific alcohol intake in a population-based study: evidence for a positive association between pulmonary function and wine intake.

BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. METHODS: We expressed pulmonary function as percent of predicted normal FEV1 (FEV1%) and FVC (FVC%) after adjustment for height, age, gender and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage specific recent (past 30 days) and lifetime alcohol consumption. RESULTS: Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors and for FEV1%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV1% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than for white wine. CONCLUSION: While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist.

Journal Article↗

Lung function in relation to intake of carotenoids and other antioxidant vitamins in a population-based study.

Accumulating evidence suggests that dietary antioxidant vitamins are positively associated with lung function. No evidence exists regarding whether dietary carotenoids other than beta-carotene are related to pulmonary function. In 1995--1998 the authors studied the association of forced expiratory volume in 1 second and forced vital capacity as the percentage of the predicted value (FEV(1)% and FVC%, respectively) after adjustment for height, age, gender, and race with the intakes of several carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene) in a random sample of 1,616 men and women who were residents of western New York State, aged 35--79 years, and free from respiratory disease. They observed significant associations of lutein/zeaxanthin and vitamins C and E with FEV(1)% and FVC% using multiple linear regression after adjustment for total energy intake, smoking, and other covariates. When they analyzed all of these antioxidant vitamins simultaneously, they observed the strongest association of vitamin E with FEV(1)% and of lutein/zeaxanthin with FVC%. The differences in forced expiratory volume in 1 second and forced vital capacity associated with a decrease of 1 standard deviation of dietary vitamin E or lutein/zeaxanthin were equivalent to the influence of approximately 1--2 years of aging. Their findings support the hypothesis that carotenoids, vitamin C, and vitamin E may play a role in respiratory health and that carotenoids other than beta-carotene may be involved.

Adult↗

Exposures associated with serum organochlorine levels among postmenopausal women from western New York State.

BACKGROUND: Organochlorines, such as 2,2-bis (4-chlorophenyl)-1,1-dichloroethylene (DDE), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are lipophilic compounds that are ubiquitous in the environment and may cause adverse health effects in humans. METHODS: We examined the correlation between epidemiological exposure variables and serum DDE, PCB, and HCB levels in a sample of 192 healthy, female postmenopausal western New York residents; a subset of the control group from a case-control study on breast cancer risk. Usual diet, reproductive and medical histories, and other lifestyle information were obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, and 69 PCB congeners were determined by gas chromatography with electron capture detection. Statistical analyses included computations of crude and age and lipid adjusted correlation coefficients, as well as multiple linear regression analysis. RESULTS: Results indicated that the strongest predictors for serum DDE levels were age, serum lipids, parity, and fruit and dairy consumption. Statistically significant predictors of PCB levels included age, serum lipids, parity, and fish consumption. Serum HCB levels were related to age, serum lipids, and fruit and red meat consumption. CONCLUSIONS: Our findings are consistent with previous investigations that reported strong associations between organochlorine levels and age and serum lipids. The absence of other data showing an association between fruit intake and organochlorine levels make the importance of this finding unclear.

Age Factors↗

Evidence for a positive association between pulmonary function and wine intake in a population-based study.

BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcoholic beverages may be an important source of oxidants and antioxidants. We analyzed the relation of beverage-specific alcohol intake with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. METHODS: We expressed pulmonary function as percent of predicted normal FEV1 (FEV1%) and FVC (FVC%) after adjustment for height, age, gender, and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage-specific recent (past 30 days) and lifetime alcohol consumption. RESULTS: Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors, and for FEV1%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV1% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than with white wine. CONCLUSION: While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist.

Adult↗

Urinary estrogen metabolites and prostate cancer: a case-control study in the United States.

OBJECTIVE: To analyze the association of prostate cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1), in a case-control study conducted in Buffalo, NY, between 1998 and 2001. METHODS: One hundred and thirteen men, aged 45-85 years, with incident, primary pathologically confirmed prostate cancer were enrolled in the study; 317 residence-matched controls were also enrolled. Cases were enrolled and the specimens collected before starting any therapy. To exclude latent prostate carcinomas, the present study included only patients with clinically apparent disease (stage B and higher). Prostate cancer cases and control subjects were excluded if on hormonal treatment, or affected with metabolic or endocrine diseases. Control subjects with a prostate-specific antigen (PSA) value higher than 4 ng/ml were excluded from the control group. Urine was used for the determinations of 2-OHE1 and 16alpha-OHE1. Age, race, body weight, waist-to-hip ratio, and smoking were analyzed as possible confounders. RESULTS: Althpugh the results were not statistically significant, elevated 2-OHE1 urinary levels suggested a reduced prostate cancer risk: men in the highest tertile had an adjusted odds ratio (OR) for prostate cancer of 0.83 (95% confidence interval (CI) 0.43-1.44). Conversely, elevated 16alpha-OHE1 urinary levels were associated with an increased risk of prostate cancer: the highest tertile had an adjusted OR for prostate cancer of 1.69 (95% CI 0.93-3.06, p for linear trend = 0.02). Finally, the 2-OHE1 to 16alpha-OHE1 ratio was associated with a reduced risk of prostate cancer with an OR of 0.61 (95% CI 0.33-1.15, p for linear trend = 0.04). CONCLUSION: Results of this case-control study suggest that the estrogen metabolic pathway favoring 2-hydroxylation over 16alpha-hydroxylation may reduce risk of clinically evident prostate cancer.

Adenocarcinoma↗

Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies.

BACKGROUND: More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consumption and to assess whether non-dietary risk factors modify the relation. METHODS: We combined the primary data from eight prospective cohort studies from North America and Western Europe with at least 200 incident breast cancer cases, assessment of usual food and nutrient intakes, and a validation study of the dietary assessment instrument. The pooled database included 351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow-up. RESULTS: We found no significant association between intakes of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast cancer risk. Categorical analyses suggested a J-shaped association for egg consumption where, compared to women who did not eat eggs, breast cancer risk was slightly decreased among women who consumed < 2 eggs per week but slightly increased among women who consumed > or = 1 egg per day. CONCLUSIONS: We found no significant associations between intake of meat or dairy products and risk of breast cancer. An inconsistent relation between egg consumption and risk of breast cancer merits further investigation.

Animals↗

The risk of breast cancer associated with dietary lignans differs by CYP17 genotype in women.

Lignans are plant compounds metabolized in the gut to produce the phytoestrogens enterolactone and enterodiol. Reduced breast cancer risks associated with higher urinary lignan excretion may be related to competitive inhibition of endogenous estrogens. Evidence exists that associations with reproductive risk factors for breast cancer differ according to cytochrome P450c17alpha (CYP17) genotype. Genetic variability in estrogen metabolism could affect lignan metabolism thereby modifying risk associations. We examined breast cancer risk, dietary lignans and CYP17 genotype among 207 women with primary, incident, histologically confirmed breast cancer and 188 controls frequency matched to cases by age and county of residence. Self-reported frequency of intake of 170 foods and beverages during the 2 y before the interview and other relevant data were collected by detailed in-person interviews. Dietary lignan intake was expressed as the sum of enterolactone and enterodiol production from foods. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education and other breast cancer risk factors. Women in the highest tertile of dietary lignans tended to have reduced breast cancer risk (OR 0.45, 95% CI 0.20-1.01 and OR 0.59, 95% CI 0.28-1.27, pre- and postmenopausal women, respectively). Substantially reduced risks in the highest tertile of lignans were observed for premenopausal women with at least one A2 allele (OR 0.12, 95% CI 0.03-0.50). Our results suggest that CYP17 genotype may be important in modifying the effect on breast cancer risk of exogenous estrogens, particularly for premenopausal women.

4-Butyrolactone↗

Impact of losses to follow-up on diet/alcohol and lung cancer analyses in the New York State Cohort.

The main objective of the study was to evaluate whether passive surveillance methods can be used in cohort studies without a significant distortion of risk estimates when the active follow-up of every participant is not possible. A nested case-control study including 525 lung cancer cases and 525 controls was conducted among participants of the New York State Cohort Study (n = 57,968 men and women), which allowed the active follow-up of a sample of the cohort and the assessment of the effect of losses to follow-up. Although there were some differences with respect to dietary intake between controls lost to follow-up and those located, the results of the nested case-control study including and excluding losses to follow-up were comparable. Moreover, the results derived from the passive and the active follow-up data were similar. Our findings lent credence to passive follow-up methods and suggested that losses to follow-up did not compromise the validity of the study. Although attempts to trace every participant are preferable in a cohort study, passive surveillance may yield unbiased risk estimates when a rare disease is being investigated.

Aged↗

Dietary fat and risk of lung cancer in a pooled analysis of prospective studies.

Lung cancer rates are highest in countries with the greatest fat intakes. In several case-control studies, positive associations have been observed between lung cancer and intakes of total and saturated fat, particularly among nonsmokers. We analyzed the association between fat and cholesterol intakes and lung cancer risk in eight prospective cohort studies that met predefined criteria. Among the 280,419 female and 149,862 male participants who were followed for up to 6-16 years, 3,188 lung cancer cases were documented. Using the Cox proportional hazards model, we calculated study-specific relative risks that were adjusted for smoking history and other potential risk factors. Pooled relative risks were computed using a random effects model. Fat intake was not associated with lung cancer risk. For an increment of 5% of energy from fat, the pooled multivariate relative risks were 1.01 [95% confidence interval (CI), 0.98-1.05] for total, 1.03 (95% CI, 0.96-1.11) for saturated, 1.01 (95% CI, 0.93-1.10) for monounsaturated, and 0.99 (95% CI, 0.90-1.10) for polyunsaturated fat. No associations were observed between intakes of total or specific types of fat and lung cancer risk among never, past, or current smokers. Dietary cholesterol was not associated with lung cancer incidence [for a 100-mg/day increment, the pooled multivariate relative risk was 1.01 (95% CI, 0.97-1.05)]. There was no statistically significant heterogeneity among studies or by sex. These data do not support an important relation between fat or cholesterol intakes and lung cancer risk. The means to prevent this important disease remains avoidance of smoking.

Case-Control Studies↗

Fasting glucose is a risk factor for breast cancer: a prospective study.

There is some evidence that glucose and other factors related to glucose metabolism, such as insulin and insulin-like growth-factors (IGFs) may contribute to breast cancer development. The present study analyzed the hypothesis that serum glucose, insulin levels, and IGF-I pattern are associated with breast cancer using a nested case-control study. Between 1987 and 1992, 10,786 women ages 35-69 were recruited in a prospective study in Italy. Women with history of cancer and on hormone therapy were excluded at baseline. At recruitment, blood samples were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants. After 5.5 years, 144 breast cancer cases were identified among the participants of the cohort. Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period. In premenopausal women, glucose was associated with breast cancer risk: the age, body mass index, and reproductive variable adjusted relative risk (RR) for the highest quartile of serum glucose versus the lowest was 2.8 [95% confidence interval (CI), 1.2-6.5], and P for trend was 0.02. Insulin showed a weaker association with breast cancer, the adjusted RR of the highest quartile versus the lowest was 1.7 (95% CI, 0.7-4.1), and P for trend was 0.14, whereas the adjusted RR of the highest quartile of IGF-I was 3.1 (95% CI, 1.1-8.6), and P for trend was 0.01. Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk: the adjusted RR for the highest quartile was 2.1 (95% CI, 0.95-4.75), and P for trend was 0.02. In postmenopausal women, the associations of glucose, insulin, and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26. These results indicate that chronic alteration of glucose metabolism is related to breast cancer development.

Adult↗