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Biomedical subjects

P Muti

Publications and source records attributed to P Muti.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Why and how to measure urinary sex steroid metabolites in epidemiological studies in women.

BACKGROUND AND AIM: Although numerous investigations have evaluated the association between urinary hormone levels and chronic diseases such as breast cancer and coronary heart disease, there are few data about the reliability of urinary measurements, particularly among premenopausal women. METHODS AND RESULTS: Over a six-month period, levels of estrone-3-glucuronide and pregnandiol-3-glucuronide were measured in both morning spot and overnight urine samples from seven healthy premenopausal women (ages 33-46). During this period, each subject provided one morning spot urine sample and one overnight urine sample per menstrual cycle on the same day of her menstrual cycle. All these samples were taken out of the freezer simultaneously and sent in the same parcel on dry ice to the laboratory for hormone determinations. All samples from each person were assayed simultaneously in the same run and by the same laboratory technician in a blind fashion. The intraclass correlation coefficients (ICC) for estrone-3-glucuronide and pregnandiol-3-glucuronide for the morning spot and overnight urine samples were 0.78 and 0.46 and 0.75 and 0.64 respectively. CONCLUSIONS: These data suggest that morning spot urine determinations are reliable and constitute an efficient alternative to the more complex overnight urine collection for epidemiological evaluation of urinary hormonal profiles.

Adult↗

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↗

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↗

Comparability of nutrient estimation by three food frequency questionnaires for use in epidemiological studies.

Replication of results is an important issue in studies of diet and disease, possibly dependent on data collection method. We compared assessments from the Health Habits and History Questionnaire (HHHQ), the Harvard Semiquantitative Food Frequency Questionnaire (HFFQ), and the New York State Cohort Food Frequency Questionnaire (CFFQ) for estimates of daily intakes of energy, protein, carbohydrates, total fat, dietary fiber, cholesterol, vitamins A, C, and E, and carotenoids. Fifty-nine men and 50 women aged 35-73 years completed the HHHQ and HFFQ as interviews and the 44-food CFFQ as a self-administered mailed questionnaire. Comparability was assessed with Spearman correlation coefficients. Quantitation of nutrient intake differed by nutrient, questionnaire, and nutrient calculation method. Ranking on energy and macronutrient intake for the HHHQ and HFFQ ranged from 0.62 to 0.80; ranking for micronutrient intake ranged from 0.56 to 0.80. For the CFFQ with the HHHQ or HFFQ, correlations ranged between 0.29 and 0.62. The CFFQ performs comparably to the HHHQ and HFFQ for some, but not all, nutrients; our results suggest that the HHHQ and HFFQ can be used interchangeably with reasonable confidence in studies of diet and disease.

Adult↗

The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group.

Many observations indicate that women have a much longer expectancy of life than men. Some population-based studies on cancer patients support the idea of the role of gender in predicting survival. However, the data are somewhat contrasting and inconclusive. The purpose of this paper was to evaluate the prognostic role of gender for cancer patients, making use of the large set of survival data made available by the EUROCARE II project for the period 1985-1989. By applying a multivariate approach the major confounders such as age, geographical area and cancer site were considered in analysing survival data on more than 1 million cancer cases collected by 45 population-based cancer registries in 17 European countries. The results were consistent with the general observation that in the industrialised countries women tend to survive longer than men. The multivariate analysis showed better survival from cancer in women than in men, estimated as an overall 2% lower relative risk of dying. The female advantage was particularly evident in young cases, reduced in patients in middle age groups and in the oldest patients completely reversed so that at this age men had the better prognosis. Longer survival for women was not present immediately after diagnosis, but the major advantage was seen after 3 years of follow-up. The risk of death for women was significantly lower for cancer of the head and neck, oesophagus, stomach, liver and pancreas. For bladder cancer, the risk of death was significantly greater for women. These results can be explained by gender differences in sub-site distributions (head and neck and stomach) and by the differences in the stage at diagnosis (presumably bladder). However, the consistency of the data, evident only when a vast set of data is analysed, suggest that women may be intrinsically more robust than men in coping with cancer.

Adolescent↗

Alcohol consumption and total estradiol in premenopausal women.

The present paper analyzes the relation between alcohol intake and serum total estradiol in premenopausal women while attempting to control or reduce several sources of variability of serum estradiol. Sixty premenopausal women were recruited, and alcohol intake was estimated by a semiquantitative questionnaire. Interviews, anthropometric measurements, and blood drawings (after overnight fasting) were conducted twice, 1 year apart. Both blood samples were obtained on the same day of the luteal phase of the cycle, in the same month and in the same hour and minute of the day. Samples from the first drawing were stored at -80 degrees C. Serum from both drawings was assayed simultaneously and in blind fashion. A significant association between alcohol intake and estradiol was found when estradiol was averaged across the two visits (Spearman's r = 0.29; P < 0.05). To control for intraindividual variability of estradiol over time, participants were then divided into tertiles of hormone distribution for each of the two sets of measurements and classified based on their consistency in estradiol across the two visits. Women showing consistently high estradiol levels at both visits were characterized by a significantly higher alcohol intake (92.8 g/week) in comparison with those showing consistently low estradiol at both visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with consistently high estradiol was significantly higher than in the group with consistently low estradiol. The present report indicates that drinkers seem to be characterized by consistently higher estradiol than nondrinkers, and that when the variability of estradiol in premenopause is considered, it is possible to identify a relationship between alcohol intake and estradiol.

Adult↗

Lactation history and breast cancer risk.

Lifetime lactation in relation to breast cancer risk was examined in a case-control study in two counties in western New York. Cases were women age 40 years and over with incident, primary, histologically confirmed breast cancer. Controls were age- and county-frequency matched, selected from New York State driver's license records (for those less than age 65 years) and from Health Care Finance Administration Records (for those age 65 or more). Included were women with at least one livebirth (253 premenopausal and 367 postmenopausal cases and 266 premenopausal and 427 postmenopausal controls). Breast cancer risk was very weakly associated with long duration of lactation among premenopausal women; the odds ratio for at least 20 months lifetime lactation was 0.50 (95% confidence interval 0.21-1.12). Among postmenopausal women, the protective effect of lactation was restricted to women with first lactation before age 25 years (odds ratio = 0.67, 95% confidence interval 0.46-0.95). However, age at first birth was highly correlated with age at first lactation. Neither insufficient milk as a reason for not breastfeeding nor having received medication to stop milk flow was associated with increased risk. These findings are in accordance with accumulating evidence that lactation may have a weak protective effect on breast cancer risk.

Aged↗

Oxidative stress and lung function.

It has been suggested that lung function can be altered by both free radical and oxidant exposure, while antioxidant vitamin intake is positively related to lung function. However, the information on the relation of blood levels of oxidants and antioxidants to lung function is sparse. The present cross-sectional study, conducted from September 1995 to May 1996, analyzes the association between lung function measured as forced expiratory volume in 1 second (FEV1) with 1) levels of thiobarbituric acid-reactive substances in plasma (p-TBARS) and in low and very low density lipoprotein cholesterol (LDL cholesterol/VLDL cholesterol-TBARS) as indicators of lipid peroxidation and 2) compounds with antioxidant activity, erythrocytic glutathione, plasma glutathione peroxidase, trolox equivalent antioxidant capacity, and serum bilirubin, which may protect against lipid peroxidation. The analysis was carried out in 132 nonsmoking subjects aged 37-73 years who were randomly selected from the residents of Erie and Niagara counties, New York. FEV1 in percent of the predicted value (FEV1%) was negatively and statistical significantly associated with p-TBARS (r = -0.19). A negative association with borderline statistical significance was observed between FEV1% with low density lipoprotein cholesterol/very low density lipoprotein cholesterol-TBARS (r = -0.16) and glutathione (r = -0.16), while FEV1% was positively related to serum bilirubin (r = 0.15). Participants in the lowest quartile of FEV1% showed significantly higher levels of p-TBARS (p = 0.02) and lower levels of bilirubin (p = 0.04) than did those in the highest quartile. Our results suggest that increased lipid peroxidation is associated with pulmonary airway narrowing in the general population.

Adult↗

Serum sex hormone levels after menopause and subsequent breast cancer.

BACKGROUND: High levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer. PURPOSE: Using an improved study design, we assessed prospectively the relationship between the principal steroid sex hormones in serum and the subsequent occurrence of invasive breast cancer in postmenopausal women. METHODS: Four thousand fifty-three healthy postmenopausal women aged 40-69 years, were enrolled from June 1987 through June 1992 in a prospective investigation of hormones and diet in the etiology of breast tumors (ORDET study) as part of a larger volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese Province, northern Italy. At recruitment, blood samples were taken between 8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in -80 degree Celsius freezers. Women who had received hormone treatment in the 3 months prior to enrollment, who had bilateral ovariectomy, or who had a history of cancer or liver disease were not recruited. Twenty-five women in the final eligible cohort of postmenopausal women developed histologically confirmed, invasive breast cancer during the first 3.5 years of follow-up for the cohort (13 537 women-years). For each case subject, four control subjects were randomly chosen after matching for factors possibly affecting hormone preservation in serum. One case subject and eight control subjects were excluded because premenopausal hormonal patterns were found; thus, after also excluding the four control subjects matched to the ineligible case subject, we included 24 case and 88 control subjects. In the spring of 1994, stored sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone sulfate and estradiol (E2) by in-house radioimmunoassay and for total and free testosterone and sex hormone-binding globulin by commercially available nonextraction iodination kits. Mean differences in risk factors were tested by analysis of variance for paired data. Relative risks (RRs) were estimated by conditional logistic regression analysis. All P values resulted from two-sided tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone, and E2 were significantly higher in case subjects than in control subjects: total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone, 1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL (P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026); for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS: This prospective study provides further evidence in support of the already established association between elevated estrogen levels and breast cancer. Even more importantly, it provides new evidence that high serum testosterone levels precede breast cancer occurrence.

Adult↗

Body fat distribution, peripheral indicators of androgenic activity, and blood pressure in women.

This report analyzes the association between blood pressure and three indicators of peripheral androgenic activity (PIAAs): body fat distribution, hirsutism, and sebum production. Furthermore, it analyzes the associations among these PIAAs to understand whether they are indicators of the same androgenic pattern. The study was conducted among 314 healthy women, aged 35-69 years, participating in the baseline examination of the Study of Hormones and Diet in the Etiology of Breast Cancer (ORDET), an Italian cohort study of breast cancer. Body fat distribution was measured as the ratio of waist-to-hip circumference (waist-to-hip ratio). Three hirsutism scores were developed by use of factor analysis after nine areas of androgen-sensitive, pilo-sebaceum units of the body were examined. Sebum production was measured by a sebumeter. Results indicated a positive correlation between the waist-to-hip ratio and the lip hirsutism score (r = 0.157). Conversely, sebum production correlated negatively with both the lip hirsutism score (r = -0.154) and the waist-to-hip ratio (r = -0.153). By use of multiple regression and with adjustment for age and body mass index, the waist-to-hip ratio was found to be positively and significantly related to both diastolic and systolic blood pressure, whereas sebum production was inversely and significantly related to both diastolic and systolic blood pressure. The facial hirsutism score was positively related to systolic blood pressure, while the limb hirsutism score was inversely and significantly related to diastolic blood pressure. Finally, interrelationships among these markers of androgenic activity were found to be weak, suggesting that these markers may be under the influence of local metabolism of the androgenic steroids. Further hormonal analyses are needed to determine whether PIAA measures obtained in epidemiological settings are useful in study of androgenic patterns and blood pressure.

Adult↗

Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period.

Serum hormones have been intensively investigated in association with several chronic diseases, but limited information exists on the reliability of a number of hormone determinations. The one-year reproducibility of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone, total estradiol, insulin, C-peptide, and prolactin was studied in 60 premenopausal and 47 postmenopausal women recruited in Varese province, Italy, 1991-1992. The hormonal determinations were made in blood samples collected twice, one year apart, after 12-h fast, in the same month, day, and hour and for premenopausal women on the same day of the luteal phase of the menstrual cycle. Samples from the first drawing were stored at -80 degrees C. Samples from both drawings were assayed simultaneously and in blind fashion. Total estradiol in postmenopause was not evaluated for limitation in the sensitivity of the laboratory method. The intraclass correlation coefficient in premenopausal women was 0.85 for DHEAS, 0.60 for total testosterone, 0.66 for free testosterone, 0.81 for insulin, 0.83 for C-peptide, 0.40 for prolactin, and 0.06 for total estradiol. In postmenopausal women, the coefficient was 0.90 for DHEAS, 0.88 for total testosterone, 0.71 for free testosterone, 0.67 for insulin, 0.73 for C-peptide, and 0.18 for prolactin. These data indicate that total estradiol measured during the luteal phase has a poor intraindividual reproducibility over time, and these findings may have important implications in studies of hormones in the etiology of chronic disease.

Adult↗

Exposure to breastmilk in infancy and the risk of breast cancer.

Early childhood nutrition may affect the subsequent risk of breast cancer in adulthood. We examined the association of having been breastfed with risk of breast cancer in a case-control study of women age 40-85 years in western New York. Cases (N = 528) had newly diagnosed primary, pathologically confirmed breast cancer; controls (N = 602) were randomly selected from the same community and were frequency matched on age. Having been breastfed was associated with decreased risk. The multivariate adjusted odds ratio was 0.74, and the 95% confidence interval was 0.56-0.99. We found little difference in the association for pre- and postmenopausal women despite a much higher frequency of breastfeeding among the older women. These findings indicate that early nutriture in general and bottle feeding in particular may relate to breast cancer development in adulthood.

Adult↗