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Biomedical subjects

J L Freudenheim

Publications and source records attributed to J L Freudenheim.

At least 19 recordsLinked to original sources
PubMed2001

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Breast Neoplasms↗
PubMed2001

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.

Body Weight↗
PubMed2001

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies.

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

Adult↗
PubMed2001

Is principal components analysis necessary to characterise dietary behaviour in studies of diet and disease?

OBJECTIVE: To assess the relative ability of principal components analysis (PCA)-derived dietary patterns to correctly identify cases and controls compared with other methods of characterising food intake. SUBJECTS: Participants in this study were 232 endometrial cancer cases and 639 controls from the Western New York Diet Study, 1986-1991, frequency-matched to cases on age and county of residence. DESIGN: Usual intake in the year preceding interview of 190 foods and beverages was collected during a personal interview using a detailed food-frequency questionnaire. Principal components analysis identified two major dietary patterns which we labelled 'healthy' and 'high fat'. Classification on disease status was assessed with separate discriminant analyses (DAs) for four different characterisation schemes: stepwise DA of 168 food items to identify the subset of foods that best discriminated between cases and controls; foods associated with each PCA-derived dietary pattern; fruits and vegetables (47 items); and stepwise DA of USDA-defined food groups (fresh fruit, canned/frozen fruit, raw vegetables, cooked vegetables, red meat, poultry, fish and seafood, processed meats, snacks and sweets, grain products, dairy, and fats). RESULTS: In general, classification of disease status was somewhat better among cases (54.7% to 67.7%) than controls (54.0% to 63.1%). Correct classification was highest for fruits and vegetables (67.7% and 62.9%, respectively) but comparable to that of the other schemes (49.5% to 66.8%). CONCLUSIONS: Our results suggest that the use of principal components analysis to characterise dietary behaviour may not provide substantial advantages over more commonly used, less sophisticated methods of characterising diet.

Case-Control Studies↗
PubMed2001

The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population.

Reduced pulmonary function is an important predictor of mortality in the general population, and antioxidant vitamins are thought to positively influence pulmonary function. Vitamin C, vitamin E, retinol, and carotenoids are powerful antioxidants but information about the joint relation of serum levels of these antioxidants to pulmonary function is limited. We analyzed the association of FEV(1) and FVC with serum vitamins C and E, retinol, and carotenoids (beta-cryptoxanthin, lutein/zeaxanthin, beta-carotene, and lycopene) in a cross-sectional study. The analysis was carried out in a sample of 1,616 randomly selected residents of Western New York, USA, age 35 to 79 yr and free of respiratory disease. Lung function was adjusted for height, age, sex, and race and expressed as percentage of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%). Participants in the lowest quartile of each of the serum antioxidants had consistently lower FEV(1)% and FVC% than those in higher quartiles. Multiple linear regression analysis revealed significant associations of vitamin C, vitamin E, beta-cryptoxanthin, lutein/zeaxanthin, beta-carotene, and retinol with FEV(1)% when these variables were investigated individually after adjustment for other covariates (smoking status, pack-years of smoking, weight, eosinophil count, and education). When all of these antioxidant vitamins were analyzed simultaneously in a multivariate regression model, the strongest association was seen with vitamin E and beta-cryptoxanthin. Only retinol showed an independent effect on FEV(1)% after controlling for vitamin E and beta-cryptoxanthin. As for FEV(1)%, vitamin E and beta-cryptoxanthin were most strongly related to FVC% when all variables were considered in the multivariate regression model. The differences in FEV(1) associated with a reduction of one standard deviation of serum vitamin E or beta-cryptoxanthin were equivalent to the negative influence of approximately 1 to 2 yr of aging. Our findings support the hypothesis that antioxidant vitamins may play a role in respiratory health and that vitamin E and beta-cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins.

Adult↗
PubMed2001

Alcohol consumption and lung cancer: a review of the epidemiologic evidence.

A role for alcohol consumption in lung cancer etiology has been suggested in some studies, but this possible relationship has been often regarded with skepticism, with any indication of an association being attributed to confounding by cigarette smoking. The purpose of this work was to review the epidemiological evidence for an association of alcohol and lung cancer and to identify gaps in that research. The studies reviewed here provide some indication that alcohol and particularly beer intake may increase lung cancer risk after controlling for cigarette smoking. Although the evidence is not conclusive, it warrants additional consideration of alcohol as a risk factor in lung cancer etiology, independent of cigarette smoking. Recommendations for future studies are provided.

Adult↗
PubMed2000

Apolipoprotein E genetic polymorphism, serum lipoproteins, and breast cancer risk.

Apolipoprotein E (apoE) is a polymorphic gene involved in lipid metabolism with three common variant alleles (epsilon2, epsilon3, and epsilon4). The epsilon4 allele has been associated with elevated levels of cholesterol as well as greater risk of coronary heart disease and Alzheimer's disease. In this case-control study we examined whether apoE genotype affected the association between serum lipids and breast cancer risk. In a subset of a study in western New York, 260 women with incident, primary breast cancer and 332 community controls were interviewed and provided blood samples. Polymerase chain reaction-restriction fragment length polymorphism analyses of the apoE polymorphism were performed. Participants were classified as apoE2 (epsilon2, epsilon2 or epsilon2, epsilon3), apoE3 (epsilon3, epsilon3), or apoE4 (epsilon4, epsilon4 or epsilon4, epsilon3). No unconditional logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with the apoE3 genotype, there were no associations with risk for women with the apoE2 (OR=1.0; 95% CI=0. 91-1.64) or apoE4 genotype (OR=0.97; 95% CI=0.63-1.54). Higher serum levels of total cholesterol, HDL cholesterol, and LDL cholesterol were not associated with risk, either in the total sample or among subgroups of women defined by apoE genotype. Women with the highest serum triglyceride levels had an increase in risk (OR=1.63; 95% CI=1. 03-2.59) compared to women with the lowest levels. This effect was not apparent among women with the apoE2 or apoE3 genotype, but much stronger among women with the apoE4 genotype (OR=4.69; 95% CI=1. 49-14.7). These data suggest that the apoE4 genotype may modify the association between serum triglycerides and breast cancer risk.

Aged↗
PubMed2000

Short-term storage of blood samples and DNA isolation in serum separator tubes for application in epidemiological studies and clinical research.

PURPOSE: To investigate the use of a simple DNA isolation technique for application in epidemiologic studies. To analyze systematically the potential impact of lag time between blood drawing and DNA isolation and the condition of storage of blood samples on the quantity and quality of isolated DNA in large-scale epidemiologic studies. METHODS: A modified single tube DNA isolation technique was used. DNA was isolated from samples collected from six participants and processed in triplicate: a) without delay after blood drawing; b) after blood cells were stored at 4 degrees C for 7 days; c) after blood cells were stored at -70 degrees C for 7 days; and d) after storage for 7 days at -70 degrees C with addition of lysis/digestion buffer. Polymerase chain reaction (PCR) and Southern blot analysis were performed to analyze the quality of the isolated DNA. RESULTS: The average amount of DNA isolated ranged from 27.0 to 71.1 microg/4.5 ml whole blood. Storage at 4 degrees C yielded, on the average, 20% less DNA than the samples processed without delay or after storage at -70 degrees C, although this difference was not statistically significant. All four conditions studied allowed isolation of highly pure DNA suitable for genetic analyses by Southern blot analysis and polymerase chain reaction. CONCLUSIONS: This pilot study suggests that storage for 7 days and at different temperatures allows isolation of high quality DNA. Using the described technique, storage of up to 7 days permits processing of large numbers of samples (50-70) in a single day, allowing for a reliable and cost-efficient way of processing in various settings. Further studies are needed to investigate the influence of long-term storage of biological specimens on DNA isolation and quality.

Blood Banks↗
PubMed2000

Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy).

OBJECTIVE: Insulin resistance and increased levels of serum steroids have been hypothesized to be relevant etiological factors for breast cancer. Measurements of markers of insulin resistance and elevated serum steroids may identify women at high risk for breast cancer. The present study analyzed the association of breast cancer with markers of insulin resistance and elevated serum sex steroids, abdominal adiposity, increase in sebum production and hirsutism in a case-control study nested in a prospective cohort study. METHODS: Between 1987 and 1992, 10,786 women (aged 35-69) were recruited in a prospective study on breast cancer in Italy, the ORDET study. Women with a history of cancer and on hormone therapy were excluded at baseline. At recruitment, abdominal adiposity was calculated from the ratio of waist-to-hip circumferences. Sebum production was measured on the forehead under standardized conditions using a sebumeter. Nine androgen-sensitive body areas were evaluated for hirsutism and a total hirsutism score was computed. After an average of 5.5 years of follow-up, 144 breast cancer cases were identified among the participants of the cohort. For each breast cancer case, four matched controls were randomly chosen from members of the cohort who did not develop breast cancer during the follow-up period. RESULTS: Waist-to-hip ratio was associated with breast cancer in premenopausal women: age and body mass index (BMI) adjusted relative risk (RR) for the highest tertile of waist-to-hip ratio was 2.2 [95% confidence interval (CI) 1.04-4.75], p for trend 0.03. In the analysis conducted within strata of BMI, the effect of waist-to-hip ratio was confined to the group of thinner women: RR for the highest tertile of waist-to-hip ratio was 3.4 (95% CI 1.2-9.5). Sebum production and hirsutism were associated with breast cancer among postmenopausal women. Age and BMI adjusted RRs for the upper tertiles were 2.2 (95% CI 1.1-4.6), p for trend 0.01, and 2.3 (95% CI 1.1-4.9), p for trend 0.03, for sebum and hirsutism, respectively. CONCLUSION: These results add evidence for a role of hormones and metabolic alterations in breast cancer etiology and for different relations of these risk factors with breast cancer in premenopausal and postmenopausal women.

Abdomen↗
PubMed2000

Diet in the epidemiology of endometrial cancer in western New York (United States).

OBJECTIVES: We examined diet and risk of endometrial cancer among women in the Western New York Diet Study (1986-1991). METHODS: Self-reported frequency of use of 172 foods and beverages during the 2 years before the interview and other relevant data were collected by detailed interviews from 232 endometrial cancer cases and 639 controls, frequency-matched for age and county of residence. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education, body mass index (BMI), smoking history, hypertension, diabetes, age at menarche, parity, oral contraceptive use, menopausal status, menopausal estrogen use, and energy. RESULTS: Risks were reduced for women in the highest quartiles of intake of protein (OR 0.4, 95% CI: 0.2-0.9), dietary fiber (OR 0.5, 95% CI: 0.3-1.0), phytosterols (OR 0.6, 95% CI: 0.3-1.0), vitamin C (OR 0.5, 95% CI: 0.3-0.8) folate (OR 0.4, 95% CI: 0.2-0.7), alpha-carotene (OR 0.6, 95% CI: 0.4-1.0), beta-carotene (OR 0.4, 95% CI: 0.2-0.6), lycopene (OR 0.6, 95% CI: 0.4-1.0), lutein + zeaxanthin (OR 0.3, 95% CI: 0.2-0.5) and vegetables (OR 0.5, 95% CI: 0.3-0.9), but unrelated to energy (OR 0.9, 95% CI: 0.6-1.5) or fat (OR 1.6, 95% CI: 0.7-3.4). CONCLUSIONS: Our results support previous findings of reduced endometrial cancer risks associated with a diet high in plant foods.

Aged↗
PubMed2000

Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women.

Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites, biologically strong estrogens, are associated with breast cancer risk, while 2-hydroxylated metabolites, with lower estrogenic activity, are weakly related to this disease. This study analyzes the association of breast cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone, in a prospective nested case-control study. Between 1987 and 1992, 10,786 women (ages 35-69 years) were recruited to a prospective study on breast cancer in Italy, the "Hormones and Diet in the Etiology of Breast Cancer" (ORDET) study. Women with a history of cancer and women on hormone therapy were excluded at baseline. At recruitment, overnight urine was collected from all participants and stored at -80 degrees C. After an average of 5.5 years of follow-up, 144 breast cancer cases and four matched controls for each case were identified among the participants of the cohort. Among premenopausal women, a higher ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone at baseline was associated with a reduced risk of breast cancer: women in the highest quintile of the ratio had an adjusted odds ratio (OR) for breast cancer of 0.58 [95% confidence interval (CI) = 0.25-1.34]. The corresponding adjusted OR in postmenopausal women was 1.29 (95% CI = 0.53-3.10). Results of this prospective study support the hypothesis that the estrogen metabolism pathway favoring 2-hydroxylation over 16alpha-hydroxylation is associated with a reduced risk of invasive breast cancer risk in premenopausal women.

Adult↗
PubMed1999

Recent alcohol intake as estimated by the Health Habits and History Questionnaire, the Harvard Semiquantitative Food Frequency Questionnaire, and a more detailed alcohol intake questionnaire.

Epidemiologic studies often rely on food frequency questionnaires (FFQs) to collect information on alcoholic beverage intake. However, estimation of alcohol intake using FFQs may be of some concern because of limited questions concerning alcohol intake. The authors compared estimates of alcohol intake during the 12-24 months prior to interview obtained from the Health Habits and History Questionnaire and the Harvard Semiquantitative Food Frequency Questionnaire with those from a more extensive alcohol questionnaire, the Drinking Pattern Questionnaire, among 133 healthy subjects (75 men, 58 women) aged 35-73 years, residents of western New York State. Data were collected in 1995 during two separate interviewer-administered computer-assisted interviews conducted approximately 2 weeks apart. For each questionnaire, average daily ounces (1 oz = 30 ml) of alcohol intake from alcoholic beverages were calculated as the product of the reported beverage-specific drink size (ounces) and the average daily frequency of intake multiplied by a factor representing the percentage of alcohol provided by each beverage. Estimates of total alcohol and liquor intake, but not of beer and wine intake, tended to be higher for the Drinking Pattern Questionnaire compared with the FFQs. Spearman's correlation coefficients ranged from 0.69 to 0.84. These results suggest that although the Drinking Pattern Questionnaire produced higher estimates than either FFQ, both FFQs provide a reasonable ranking of participants' alcohol intake.

Adult↗
PubMed1999

Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer.

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and alpha-tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer.

Aged↗
PubMed1999

Risk of premenopausal breast cancer and patterns of established breast cancer risk factors among teachers and nurses.

BACKGROUND: Contrasting results have been published regarding the risk of breast cancer among teachers and nurses. Confounding by reproductive factors may explain the increased risk observed among women in these occupations as information on those factors were not available in most studies. METHODS: We examined the risk of premenopausal breast cancer among teachers and nurses using occupational histories in a case-control study where information on established risk factors was available. RESULTS: Having ever held a teaching job was not related to breast cancer (OR = 0.74, 95% CI = 0.44-1.28) and women who worked for 10 years or less in this occupation had a non-significant deficit of risk (OR = 0.52, 95% CI = 0.27-1.02). No elevation in risk was found in association with having ever been a nurse (OR = 0.85, 95% CI = 0.45-1.61) or with duration of nursing. Although direct comparison of established risk factors among teachers and nurses and other women in the study showed some evidence of differential distribution, especially when comparing teachers to other women, adjustment for reproductive variables and other breast cancer risk factors did not change the results of this study. CONCLUSION: These findings suggest that teachers and nurses are not at an increased risk of breast cancer. This study also suggests that established risk factors for premenopausal breast cancer may not explain the elevation of risk found in other studies of teachers and nurses. However, this conclusion is limited by the fact that in the present study teachers and nurses had lower than expected breast cancer risk with or without adjustment for established risk factors. Limitations of this study such as low response rates and limited statistical power should be considered in the interpretation of these findings.

Adult↗
PubMed1999

An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units.

BACKGROUND: Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However, to date there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. METHODS: In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. RESULTS: Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. CONCLUSIONS: In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed.

Aged↗
PubMed1999

Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk.

OBJECTIVES: Because alcohol dehydrogenase 3 (ADH3) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH3 genotype in relation to alcohol intake and breast cancer risk. METHODS: We conducted a case-control study among Caucasian women aged 40-85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression. RESULTS: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7-1.7) associated with ADH3(1-1) compared to ADH3(1-2) and ADH3(2-2) genotypes. Risk was increased for premenopausal women with the ADH3(1-1) genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5-8.8) compared to lighter drinkers with the ADH3(2-2) or ADH3(1-2) genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption. CONCLUSION: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk.

Adult↗
PubMed1999

Study design and hypothesis testing: issues in the evaluation of evidence from research in nutritional epidemiology.

In addressing questions about the relations of dietary factors to disease in human populations, epidemiologic studies must account for the complexity of dietary habits, the intercorrelations among dietary habits, and the correlations of those habits with other behaviors. Furthermore, for studies of chronic disease, relevant dietary exposures may occur over decades. The classic epidemiologic study designs have been used to examine the associations between diet and disease; the strengths and weaknesses of those designs must be considered. Concerns have been raised regarding the validity of the measures of diet, the differential recall of diet by diseased individuals in case-control studies, and confounding by other related factors in both case-control and cohort studies. In clinical trials there may be difficulties in effecting the necessary dietary changes, especially for macronutrients, and there are also concerns about those circumstances in which participants cannot be blinded to their treatment. For case-control and cohort studies and for some clinical trials, intercorrelations among nutrients are a concern in the identification of factors that are important in the etiology of disease. It is important to understand these considerations when interpreting nutritional epidemiologic studies for the purpose of setting public policy. No one study can be considered definitive in the understanding of a diet-disease relation. However, epidemiologic findings from multiple studies taken together can contribute significantly to our understanding of diet in relation to disease in humans.

Bias↗