Biomedical subjects

P Muti

Publications and source records attributed to P Muti.

At least 19 recordsLinked to original sources

PubMed2006

Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD.

OBJECTIVE: The objective of this study was to investigate the association between antioxidant nutrients and markers of oxidative stress with pulmonary function in persons with chronic airflow limitation. DESIGN: Cross-sectional study exploring the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). SETTING/SUBJECTS: The study data included 218 persons with chronic airflow limitation recruited randomly from the general population of Erie and Niagara counties, New York State, USA. RESULTS: After adjustment for covariates, multiple linear regression analysis showed that serum beta-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, vitamin C, and lycopene were positively associated with FEV1% (P < 0.05, all associations). Serum vitamins beta-cryptoxanthin, lutein/zeaxanthin, and lycopene, and dietary beta-cryptoxanthin, beta-carotene, vitamin C, and lutein/zeaxanthin were positively associated with FVC% (P < 0.05, all associations). Erythrocytic glutathione was negatively associated with FEV1%, while plasma thiobarbituric acid-reactive substances (TBARS) were negatively associated with FVC% (P < 0.05). CONCLUSION: These results support the hypothesis that an imbalance in antioxidant/oxidant status is associated with chronic airflow limitation, and that dietary habits and/or oxidative stress play contributing roles.

Antioxidants↗

PubMed2004

Oxidative stress and glucose levels in a population-based sample.

OBJECTIVES: To examine the relationship between markers of oxidative status and glucose on a population basis. STUDY DESIGN AND SETTING: We report here on a population-based sample of 1315 women and 981 men, aged 35-79 years, randomly selected from residents of Erie and Niagara Counties in western New York between 1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as markers of oxidative status. Study sample was categorized by quartiles of glucose, degree of abnormality of fasting glucose, and level of metabolic control in patients with diabetes. RESULTS: Men and women in the uppermost quartiles of glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 = 1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/- 0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting glucose, impaired fasting glucose was associated with higher levels of TBARS (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs. 1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64 vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/- 0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than normal or impaired fasting glucose. In men, abnormal fasting glucose was associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/- 0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/- 13.25 vs. 579.42 +/- 27.42 IU/l). CONCLUSIONS: Glucose levels play a role in determining oxidative status in a population sample. The balance between oxidative and antioxidant processes appears to be sensitive to glucose levels with moderate elevations of glucose affecting the oxidative status.

Aged↗

PubMed2004

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Adult↗

PubMed2003

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aged↗

PubMed2003

Alcoholic beverage preference and characteristics of drinkers and nondrinkers in western New York (United States).

BACKGROUND AND AIM: Dietary and lifestyle characteristics may differ for drinkers of specific alcoholic beverages and nondrinkers which would have important implications for studies of alcohol and disease. Our aim in this study was to describe differences in dietary and lifestyle characteristics associated with alcoholic beverage preference in a population-based sample of healthy study participants. METHODS AND RESULTS: Data were collected as part of a series of case-control studies of alcohol use, myocardial infarction, and lung, breast and prostate cancer in western New York from 1846 men and 1910 women aged 35 to 79, randomly selected from the general population of Erie and Niagara Counties. Beverage preference was defined for noncurrent vs current drinkers, and drinkers of beer, wine, liquor, and mixed beverages. Generalized linear models for continuous variables and Cochran-Mantel-Haenszel statistics for categorical variables were computed for the entire sample and stratified by gender. Participant characteristics differed by alcoholic beverage preference and drinking status. In general, wine drinkers had higher education and household incomes, lower prevalence of current smoking, higher intakes of dietary fiber, potassium, vitamin E, and total carotenoids, lower total fat intakes and higher amounts of fruits, vegetables, and grain products than consumers of other beverages. Conversely, beer and liquor drinkers had somewhat lower education and household incomes, higher rates of current smoking, higher energy and total fat intakes and consumed lower amounts of fruits, vegetables, and grain products. Finally, current nondrinkers were more likely to be older, less educated, have lower household incomes, and consume diets less consistent with dietary guidelines than current drinkers. CONCLUSIONS: These results suggest that usual beverage preference may encompass other health-related behaviors and underline the importance of accurate exposure measurement and use of statistical methods to accommodate these interrelationships.

Adult↗

PubMed2002

Minimal and best linear combination of oxidative stress and antioxidant biomarkers to discriminate cardiovascular disease.

BACKGROUND AND AIM: Free radicals have been implicated in the atherosclerotic process of coronary heart disease (CHD). Well-developed laboratory methods may make available a large number of biomarkers of individual oxidative stress and antioxidant status. Such markers are able to quantify different phases of the oxidative stress and antioxidant status of an individual. However, limited knowledge is available on how to combine these biomarkers to best discriminate between individuals with and without CHD. METHODS AND RESULTS: We evaluated combined discrimination properties of six biomarkers of oxidative stress and antioxidant status, as indicators of CHD, in a cross-sectional random sample of 968 white men and women from Buffalo, New York. Individuals with CHD had significantly higher levels of thiobarbuturic acid reacting substances (TBARS) and uric acid, and significantly lower levels of high-density lipoproteins (HDL) after adjusting for age and gender, when compared to healthy subjects. There were no significant differences in erythrocyte glutathione (GSH), trolox equivalent antioxidant capacity (TEAC), and glutathione peroxidase (GSHPx) levels. TBARS were found to be the best discriminating of the biomarkers when it was individually evaluated. TBARS discriminate 76.2% (95% C.I. 0.66-0.82) of the CHD cases from healthy controls. When combining TBARS, GSH, TEAC, HDL, uric acid and GSHPx, they discriminate 81.5% (95% C.I.: 0.67-0.90) of the area under the curve. CONCLUSIONS: These preliminary findings suggest that the combination of multiple markers of oxidative stress does not greatly improve ability to differentiate between individuals with and without CHD compared to the use of TBARS alone.

Adult↗

PubMed2001

Correlates of markers of oxidative status in the general population.

Oxidative stress has been implicated in the etiology of many chronic diseases, including cardiovascular disease. However, limited information exists on the factors that may influence oxidative status in the general population. In a random sample of the population of two counties in western New York, levels of several markers of oxidative status (i.e., thiobarbituric acid-reactive substances, erythrocyte glutathione, and glutathione peroxidase) were determined. A total of 894 men and 903 women aged 35-79 years were included in the study (1996-1999). In addition, a number of sociodemographic and lifestyle characteristics and cardiovascular disease risk factors were measured. Age, markers of glucose metabolism (e.g., plasma glucose level) and insulin resistance (e.g., serum triglycerides, high density lipoprotein cholesterol, body mass index), and postmenopausal status in women were associated with increased oxidative stress and reduced antioxidant potentials. Oxidative status and antioxidant potentials appear to be significantly associated with a number of major cardiovascular disease risk factors; most of them are linked to abnormalities in glucose and insulin metabolism.

Adult↗

PubMed2001

Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study.

BACKGROUND: The relationship between erythrocyte membrane fatty acids and postmenopausal breast cancer risk was analyzed previously only by retrospective studies, which suggested a protective effect of increased saturation index (SI), i.e., the ratio of membrane stearic to oleic acid. We investigated the relationships in a prospective study of hormones, diet, and prediagnostic breast cancer (the ORDET study) conducted in northern Italy. METHODS: A total of 4052 postmenopausal women were followed for an average of 5.5 years; 71 cases of invasive breast cancer were identified. For each case subject, two matched control subjects were chosen randomly from among cohort members. The various fatty acids in erythrocyte membranes were measured as a percentage of total fatty acids. Conditional logistic regression analysis evaluated the association between membrane fatty acid composition and breast cancer risk. The SI, which is influenced by the activity of the enzyme delta 9 desaturase (Delta 9-d), was also investigated. All statistical tests were two-sided. RESULTS: Oleic (highest versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer risk, but individual polyunsaturated fatty acids behaved differently. There was no association between saturated fatty acids and breast cancer risk. CONCLUSIONS: We have found that monounsaturated fats and SI in erythrocyte membranes are predictors of postmenopausal breast cancer. Both of these variables depend on the activity of the enzyme Delta 9-d. The dietary, metabolic, and hormonal factors acting on Delta 9-d expression and activity and, therefore, on patterns of fatty acid metabolism, should be further investigated as possible determinants of breast cancer.

Adult↗

PubMed2001

Measurement variability of plasma beta-sitosterol and campesterol, two new biomarkers for cancer prevention.

Phytosterols are plant sterols that are structurally similar to cholesterol and are characterized by anti-carcinogenic and anti-atherogenic properties. Beta-sitosterol and campesterol are the predominant phytosterols in blood. The present study aimed to analyse the reproducibility and overtime reliability of plasma beta-sitosterol and campesterol measurements. In order to study the reproducibility of the measurement (technical variability), three healthy premenopausal women donated a sample of their blood. Each blood sample was subdivided into six aliquots and analysed within the same run by the same laboratory technician. The intraclass correlation coefficients (ICCs) of the assay for plasma beta-sitosterol and campesterol were 0.88 and 0.94 (95% confidence intervals low bounds (95% CI(low)) were 0.66 and 0.82), respectively. To study the reliability of beta-sitosterol and campesterol measurement over time, seven premenopausal women were recruited. Over a 6-month period, each woman provided a fasting blood sample once a month at the same time of day, and the same numerical day of the luteal phase of her menstrual cycle (between the 20th and 24th day of her menstrual cycle). All plasma samples from the same individual were processed together at the same time by the same technician at the end of the 6-month period. The overtime ICCs of plasma beta-sitosterol and campesterol were 0.91 (95% CI(low) 0.49) and 0.58 (95% CI(low) 0.31), respectively. The high reproducibility and good overtime reliability of plasma beta-sitosterol and campesterol measurements indicate that they may be suitable for potential clinical and population-based studies on cancer prevention.

Adult↗

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

TBARS and cardiovascular disease in a population-based sample.

BACKGROUND: Oxygen radicals might play a crucial role in the pathogenesis of various diseases, including atherosclerosis. Thiobarbituric acid reaction substances (TBARS), a biomarker of oxidative stress, have been proposed as a summary measure of total circulating oxidation. However, there is no strong indication that circulating levels of TBARS are increased in patients with atherosclerosis. DESIGN: We evaluated the relation between TBARS and cardiovascular disease (CVD) in a cross-sectional random sample of white men and women from Buffalo, New York. METHODS: Logistic regression was used to estimate the risk associated with high levels of TBARS. The area under the ROC curve was used to evaluate the discriminating power of TBARS. RESULTS: After adjusting for age and gender, TBARS levels were significantly higher in those with prevalent CVD (OR= 1.73, 95% CI=1.32-2.38), compared to those without a CVD diagnosis. These OR were almost 50% higher after correcting for measurement error (ME) (OR=1.93, 95% CI=1.07-3.40). The area under the ROC curve was 0.69 (95% CI=0.62-0.77) and when corrected for ME reached 0.80 (95% CI=0.65-0.89). CONCLUSIONS: Our results indicate that elevated levels of TBARS were associated with increase risk of the prevalence of CVD, but this effect was no longer significant after adjusting for glucose.

Adult↗

PubMed2001

Markers of insulin resistance and colorectal cancer mortality.

A link between insulin metabolism and colorectal cancer has been hypothesized, supported by a series of potential physiological mechanisms, and confirmed by a number of reports in experimental animals. However, the evidence in humans is limited and mostly indirect. The aim of the present report is to analyze whether individuals with a cluster of metabolic abnormalities associated with abnormalities in insulin metabolism experience higher mortality for colorectal cancer than those without this cluster of metabolic abnormalities. A total of 21,311 men and 15,991 women 20-69 years of age were followed-up for an average of 7 years as part of the Risk Factors and Life Expectancy Project, a pooling of a number of epidemiological studies conducted in Italy. Our analyses indicate that participants with high levels of blood glucose and a cluster of metabolic abnormalities linked to insulin resistance experienced a significant increased risk of colorectal cancer mortality compared with participants without the cluster. For the presence of the cluster of metabolic abnormalities, the calculated hazard ratios and 95% CIs were 2.96 (1.05-8.31) for men, 2.71 (0.59-12.50) for women, and 2.99 (1.27-7.01) when both sexes were combined. These associations were independent from the potential confounding effect of age, drinking of alcoholic beverages, and smoking. Our findings are supportive of the hypotheses that glucose metabolism hyperinsulinemia, insulin resistance, and metabolic abnormalities associated with it may play a significant role in the etiology of colorectal cancer.

Adult↗

PubMed2001

Differences in attitudes toward organ donation among African Americans and whites in the United States.

The availability of organs within the African-American population has been an on-going issue. Historically, African Americans donate organs at a much lower rate than whites. Thus, this study was designed to compare general attitudes between African Americans, whites, and other minorities concerning the issue of organ donation and to identify the factors that hamper African Americans from becoming organ donors. We conducted a 12-question survey of 249 African Americans, 492 whites, and a category of others defining themselves as 71 Asians, 23 Hispanics, 22 Native Americans, and 35 unknowns for a total sample of 892. Samples were taken from six United States cities. Thirty-eight percent of African Americans stated they would not donate organs, compared to 10% of whites. When asked why not, African Americans stated "personal reasons" followed by "if I am an organ donor I won't get the necessary medical attention" as their top choices. Whites chose "religious reasons" followed by "organs may be taken before I am dead" as their top choices. African Americans were more concerned with getting proper medical treatment as opposed to whites, who worried their organs might be taken before their death. Regarding family discussion pertaining to organ donation, 66% of African Americans stated no discussion. Whites had a 46% rate for no family discussion. Regarding trust of doctors, 46% of African Americans expressed lack of trust for doctors, with 23% of whites expressing lack of trust for doctors. The results of this study point to the areas that must be given more focus by African-American health care providers and educators.

Adolescent↗

PubMed2000

Fatty acid composition of the red blood cell membrane in relation to menopausal status.

PURPOSE: Menopausal status effects female anatomical functioning at a variety of system-wide and cellular levels, including cellular membrane composition. This study analyzed a nested case-control ORDET data set of 433 pre and post-menopausal breast cancer controls to examine the effects of menopausal status on the fatty acid composition of the red blood cell membrane.METHODS: ORDET is a prospective cohort study conducted in Italy to investigate the etiologic role of hormones and diet in breast cancer development. The fatty acid composition was measured and analyzed by gas chromotography, comparing retention time with standard measurement. Twenty-two individual fatty acids were measured, recorded, and categorized into four fatty acid groups: saturated, monounsaturated, polyunsaturated n-6 (PUFA n-6), and polyunsaturated (PUFA n-3) fatty acids.RESULTS: Post-menopausal women had consistently lower mean values for all four fatty acid categories and all individual fatty acids. Statistically significant mean differences, by menopausal status, were observed for three of the four fatty acid categories: saturated fatty acids (p = 0.006), PUFA n-6 acids (p = 0.001), and PUFA n-3 acids (p = 0.000). The biggest statistically significant differences in mean values among individual fatty acids for each category were observed for Palmitic acid (p = 0.009), Oleic acid (p = 0.040), Linoleic acid (p = 0.000), and Docosahexaenoic acid (p = 0.000). Individual fatty acids were also less highly correlated among post-menopausal women.CONCLUSIONS: There was an observed relationship between menopausal status and the fatty acid composition of the red blood cell membrane that warrants further study. This relationship may contribute to the physiological and psychological changes that occur during and after menopause, and may have far-reaching implications for women's health.

Journal Article↗

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

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↗

PubMed2000

Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia.

In children with acute lymphoblastic leukaemia (ALL) treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group, the initial response to prednisone is the strongest predictor of therapy outcome. Glutathione S-transferases (GSTs) have been implicated in glucocorticoid resistance. In order to assess a potential association of phenotypically relevant GST polymorphisms with prednisone response in childhood ALL, we conducted a case-control study of 45 prednisone poor-responders (cases) and 90 prednisone good-responders (controls) who were frequency matched according to initial white blood cell count. In addition, we analysed the association of GST genotypes with relapse of leukaemia. In univariate analysis, homozygous deletion of GSTT1 (null genotype) conferred a 6.7-fold reduction in risk of prednisone poor-response compared to individuals who were either heterozygous or homozygous for GSTT1 [odds ratio (OR) = 0.15, P = 0.071; multivariate odds ratio = 0.18, P = 0.117]. GSTM1 and GSTP1 genotypes did not show any association with prednisone response. In addition, risk of relapse was predicted strongest by the GSTT1 genotype. In univariate analysis, the GSTT1 null genotype conferred a 5.9-fold reduction in risk of relapse compared to the heterozygous or homozygous presence of GSTT1 (OR = 0.17, P = 0.095; multivariate OR = 0.23; P = 0.173). No associations of the GSTM1 genotype with risk of relapse were observed. GSTP1 codon 105 and codon 114 polymorphisms were predominantely associated with central nervous system relapse. Our results add further support to the hypothesis that genetic polymorphisms within specific GST genes might be of clinical importance in childhood ALL.

Adolescent↗