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Background/Objectives:: The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population, using newly updated harmonized European Union food composition data. This work also aimed at analyzing in a holistic way the total content of the diet in major classes of polyphenols. Subjects/Methods:: Six thousand nine hundred and eighty-one men and 7048 women (aged ⩾35years) of the Moli-sani cohort, randomly recruited from the general population, were analyzed. The European Prospective Investigation into Cancer (EPIC) and Nutrition-Food Frequency Questionnaire was used for dietary assessment. The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables (FCTs), when data were missing. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated and polyphenol antioxidant content (PAC) score (−28, 28) constructed, to assess the total content of the diet in these nutrients. Results:: Seasonal and citrus fruits, leafy, grain, pod and root vegetables, and onions and garlic accounted for different proportions (11–70%) of the total intake of different polyphenols. Within the Moli-sani population, men or older, or no/former smokers, or physically active or obese/overweight individuals presented higher consumption of flavonoids, lignans and PAC score (Pfor all <0.01). Multiple regression analysis showed that PAC score and its seven components were positively associated with Mediterranean diet (MeD) adherence in both genders (β-coefficient >0, P<0.001). In addition, 1 unit increase in PAC score was associated with 7.1–7.8% increase in the likelihood of high MeD adherence (P<0.001). Conclusions:: The intake of flavonoids and lignans in an European Union population was calculated using harmonized European Union FCT data. In addition, a holistic approach in dietary analysis of polyphenol intake was proposed.

Aim: Differences in C-reactive protein (CRP) levels and its determinants in three European populations at different risk of coronary artery disease(CAD) were studied.Methods: Subjects were recruited randomly in Limburg (Belgium), Abruzzo (Italy) and south-west (SW) London (England).Results: Ten-year risk of fatal coronary events (estimated using risk equations provided by the SCORE Project) was lower both in men and women from Abruzzo, intermediate in people from Limburg and higher in subjects from SW London. Within each country, high sensitivity (hs)-CRP levels were higher in the high-risk class in men but not in women. Men from Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women always had higher hs-CRP levels than men. The strongest hs-CRP determinant was body mass index (BMI, R2 = 0.14) in women and waist circumference (WC, R2 = 0.046) in men. The highest hs-CRP levels were observed in subjects with both high BMI and high WC. Metabolic syndrome was associated with high levels of CRP both in men and women, even after adjustment for confounders. Discussion: Difference in CRP levels cannot explain the European gradient of CVD risk, although CRP levels are associated with the calculated SCORE risk of fatal coronary events within each country.

The objective of this study is to evaluate the effect of cryopreservation at different storage temperatures on urinary 6-sulfatoxymelatonin (aMT6s) concentration. Overnight urine from 28 postmenopausal women participating in the ORDET cohort study was filtered and separated into 6 mL aliquots. Urine samples were stored at –80°C and at –30°C for an average of 14 years. Urinary aMT6s concentration was assessed using a competitive immunoassay. Mean aMT6s values of samples stored at –30°C were systematically lower than those of samples stored at –80°C (10.7 ng/mL versus 15.8 ng/mL, p<0.001). Bland Altman plots showed disagreement between determinations at different storage temperatures at the highest levels of the metabolite concentration. The degree of agreement evaluated in terms of intra-class correlation coefficient was 0.68 (95% CI 0.41–0.84, p<0.0001). Pearson's correlation coefficient between aMT6s values of the two differently stored samples was 0.93 (p<0.001), while the Kendal tau coefficient for rank distribution was 0.73 (p<0.001). Our data suggest that storage temperatures might affect degradation of aMT6s during storage. However, individual characterization by melatonin levels does not seem to be affected by cryopreservation conditions.

Objective: Aging is associated with appetite decline, weight loss, reduced fat-free mass (FFM), and increased fat mass (FM). Ghrelin and leptin are short- and long-term determinants of energy balance respectively, whose dysregulation could alter food intake. We evaluate the relationship of circulating ghrelin and leptin responses to standardized oral mixed nutrient load (SOMNL) with body composition, daily food intake, and insulin sensitivity in healthy elderly subjects (ES).Design and methods: Twenty-six ES (12/14 M/F, 69±4 years) and ten young healthy controls (LY) (5/5 M/F, 27±3 years) were studied at the International Center for the Assessment of Nutritional Status (Milan, Italy) with air plethysmography, dual energy X-ray absorptiometry, indirect calorimetry, and dietary intake assessment. Basal and postprandial ghrelin, leptin, testosterone, glucose, insulin and C-peptide concentrations, and insulin resistance (homeostasis model assessment (HOMA-R)) and sensitivity (quantitative insulin-sensitivity check index (QUICKI)) were evaluated.Results: Basal ghrelin levels were similar in ES and LY, whereas leptin was higher in ES than LY, in agreement with the higher amount of FM. Basal and percentage change in ghrelin were inversely related to FFM, appendicular skeletal muscle mass (SMM), and QUICKI, but not to FM. Basal and percentage change in leptin were directly related to FM and not to FFM indexes. Ghrelin basal concentration was negatively correlated with energy and protein intake and with QUICKI. Percentage change in Ghrelin after SOMNL correlated negatively with protein intake, but positively with resting energy expenditure and energy intake, and glucose, insulin, C-peptide basal concentrations, and HOMA-R.Conclusion: In ES, basal and postprandial ghrelin increases with FFM, specifically SMM, reduction, whereas leptin increases with relative FM increases.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral–pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case–control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16–4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27–0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05–0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02–6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02–1.61), bladder cancer (OR = 1.38, 95% CI = 1.06–1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Δ4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids –the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

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.

EPIC-Italy is the Italian section of a larger project known as EPIC (European Prospective Investigation into Cancer and Nutrition), a prospective study on diet and cancer carried out in 10 European countries. In the period 1993-1998, EPIC-Italy completed the recruitment of 47,749 volunteers (15,171 men, 32,578 women, aged 35-65 years) in 4 different areas covered by cancer registries: Varese (12,083 volunteers) and Turin (10,604) in the Northern part of the country; Florence (13,597) and Ragusa (6,403) in Central and Southern Italy, respectively. An associate center in Naples enrolled 5,062 women. Detailed information for each individual volunteer about diet and life-style habits, anthropometric measurements and a blood sample was collected, after signing an informed consent form. A food frequency questionnaire specifically developed for the Italian dietary pattern was tested in a pilot phase. A computerized data base with the dietary and lifestyle information of each participant was completed. Blood samples were processed in the same day of collection, aliquoted (RBC, WBC, serum and plasma) and stored in liquid nitrogen containers. Follow-up procedures were validated and implemented for the identification of newly diagnosed cancer cases. Cancer incidence was related to dietary habits and biochemical markers of food consumption and individual susceptibility in order to test the role of diet-related exposure in the etiology of cancer and its interaction with other environmental or genetic determinants. The comparability of information in a prospective study design is much higher than in other studies. The availability of such a large biological bank linked to individual data on dietary and life-style exposures also provides the unique opportunity of evaluating the role of selected genotypes involved in the metabolism of chemical compounds and DNA repair, potentially related to the risk of cancer, in residents of geographic areas of Italy characterized by specific cancer risk and different dietary patterns. Baseline characteristics of participants are briefly described.

AbstractObjective:To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950?1975 (at age 20), 1960?1985 (at age 30) and 1970?1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time.Setting:The EPIC project.Subjects:In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries.Results:Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950?1975, 1960?1985 and 1970?1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption.Conclusion:The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.

AbstractObjective:To describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:A cross-sectional analysis of baseline data of a European prospective cohort study.Subjects:This analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a ?health-conscious? group. The analysis was restricted to 83 178 men and 163 851 women aged 50?64 years, this group being represented in all centres.Methods:Anthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the ?health-conscious? group (UK), anthropometric measures were predicted from self-reports.Results:Except in the ?health-conscious? group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m-2. The prevalence of obesity (BMI?30 kg m-2) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (>25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (<10%) in the French centres and the ?health-conscious? group (UK). The prevalence of a large waist circumference or a high waist-to-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands).Conclusions:Anthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.

Abstractbjective:The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases.Methods:We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex.Results:Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day?1) for men and in Danish centres (Copenhagen, 20.9 g day?1) for women. The lowest total alcohol intake was in the Swedish centres (Ume?, 10.2 g day?1) in men and in Greek women (3.4 g day?1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes.Conclusions:The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.

DNA repair genes have an important role in protecting individuals from cancer-causing agents. Polymorphisms in several DNA repair genes have been identified and individuals with non-dramatic reductions in the capacity to repair DNA damage are observed in the population, but the impact of specific genetic variants on repair phenotype and cancer risk has not yet been clarified. In 308 healthy Italian individuals belonging to the prospective European project EPIC, we have investigated the relationship between DNA damage, as measured by (32)P-DNA adduct levels, and three genetic polymorphisms in different repair genes: XRCC1-Arg399Gln (exon 10), XRCC3-Thr241Met (exon 7) and XPD-Lys751Gln (exon 23). DNA adduct levels were measured as relative adduct level (RAL) per 10(9) normal nucleotides by DNA (32)P-post-labelling assay in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis. The XRCC3-241Met variant was significantly associated with higher DNA adduct levels, whereas XRCC1-399Gln and XPD-751Gln were associated with higher DNA adduct levels only in never-smokers. XRCC3-241Met homozygotes had an average DNA adduct level of 11.44 +/- 1.48 (+/-SE) compared with 7.69 +/- 0.88 in Thr/Met heterozygotes and 6.94 +/- 1.11 in Thr/Thr homozygotes (F = 3.206, P = 0.042). Never-smoking XRCC1-399Gln homozygotes had an average DNA adduct level of 15.60 +/- 5.42 compared with 6.16 +/- 0.97 in Gln/Arg heterozygotes and 6.78 +/- 1.10 in Arg/Arg homozygotes (F = 5.237, P = 0.007). A significant odds ratio (3.81, 95% CI 1.02-14.16) to have DNA adduct levels above median value was observed for XPD-751Gln versus XPD-751Lys never-smoking homozygotes after adjustment for several confounders. These data show that all the analysed polymorphisms could result in deficient DNA repair and suggest a need for further investigation into the possible interactions between these polymorphisms, smoking and other risk factors.

The relation between blood pressure and habitual physical activity during leisure time was investigated in a random sample of 272 sixth grade schoolchildren (mean age, 11.3 years) who entered secondary school in 1983 in Marano di Napoli, a suburb of Naples, Italy. Blood pressure, pulse rate, and anthropometry were measured with standardized techniques. Physical activity was evaluated by a questionnaire outlining four levels of physical activity during leisure time. The study provided evidence that a low level of physical activity during leisure time in 11-year-old children is associated with higher systolic blood pressure independent of sex, age, and adiposity. These findings may be relevant to programs of primary prevention of arterial hypertension in early life.

The present report analyzes the relation between different categories of consumption of varied calcium-rich foods and blood pressure in a population sample of 5,049 Italian men and women aged 20-59, examined between November 1978 and May 1979. The consumption pattern of the various foods was estimated with the use of a food frequency questionnaire. The findings are consistent with an inverse association between whole milk consumption and systolic, but not diastolic, blood pressure. Daily consumption of cheese, on the other hand, is not associated with reduced blood pressure levels. The possibility of an adverse effect of the high saturated fats and sodium content on blood pressure that could counteract the beneficial effect of calcium is discussed. Daily skim milk consumption is surprisingly associated with higher systolic, but not diastolic, pressure, compared with infrequent consumption. The possibility of these findings being the result of pre-existing health problems leading to the selection of skim milk over whole milk is discussed. Daily consumption of legumes is associated with lower systolic pressure than infrequent consumption, but the differences do not reach statistical significance, probably because of limited statistical power. These associations are similar in both males and females.

A pilot questionnaire was developed for the EPIC centres of northern Italy, and validated in the feasibility part of the cohort project. The questionnaire was self-administered and of the food frequency type with portion size estimated by means of pictures. It was structured by courses within a meal characteristic of Italian dietary habits. Dietary intake estimated by the questionnaire was compared to the corresponding estimates obtained from 8-14 24-hour recall interviews administered over a 1-year period. The reference method was validated by means of urinary nitrogen in 4-6 repeated 24-hour urine collections. One hundred and ninety-seven volunteers (47 men and 150 women) were enrolled and completed the study lasting 1 year. They filled out two questionnaires at the beginning and at the end of the study, and had a 24-hour recall interview once a month. Twenty-four-hour urine samples were collected at regular intervals. Usual intake of energy, the major nutrients and some vitamins were estimated for the questionnaires and the reference method by means of food composition tables compiled for this study. The agreement between the questionnaire and the 24-hour recalls was only good for alcohol consumption: Pearson's correlation was 0.73 and 0.77 in men and women respectively. Otherwise the relative validity of the questionnaire ranged between 0.28 for fat to 0.52 for carbohydrates in men and 0.25 and 0.50 in women for the same nutrients. The validity of the two interview methods in estimating protein intake, compared to mean urinary nitrogen was 0.24 (M) and 0.18 (W) for the questionnaire and 0.63 (M) and 0.48 (W) for 24-hour recalls. The main causes of low performance of the questionnaire were identified to be the estimated intake of dressing and cooking fats, vegetables and meat. Remedies were devised and introduced in the final version of the questionnaire currently in use in the EPIC project.

The purposes of this study were to determine the prevalence of perimenstrual symptoms among a randomly selected group of Italian women by using a standardized menstrual symptom instrument and to compare them with those from a census-based sample of free-living American women in the study by Woods et al. (Am J Public Health 1982;72:1257-64). Italian menstrual symptom prevalence rates were obtained as part of a 1984 national health screening project using the Moos Menstrual Distress Questionnaire translated into Italian. A total of 306 of the 426 randomly invited women between ages 20 and 49 years participated (71.8% participation rate). After determination of ineligible participants (those who were postmenopausal, posthysterectomy, and pregnant), a total of 239 subjects were interviewed. Italian women reported the highest prevalence of symptoms during the menstrual phase and the lowest prevalence during the remainder of the cycle. The cross-cultural comparison indicates that, overall, Italian women reported higher prevalence of symptoms across the three phases of the cycle than did the American women, even though this difference was the smallest during the premenstrual phase. Prevalence rates of a number of classic premenstrual symptoms (e.g., breast tenderness) and affective symptoms (e.g., tension and avoid social activities) were found to be similar for the Italian and American samples. This study, while it identifies a sociocultural component to symptom reporting, indicates the presence of premenstrual distress symptoms in diverse cultural settings, even in women who are generally unaware of premenstrual syndrome. These findings lend support to the validity of the premenstrual phase distress experience and suggest the existence of the premenstrual syndrome across diverse cultures.

The longitudinal association between a number of coronary heart disease risk factors and the experience of a natural disaster (earthquake) was analyzed in a group of workers participating in a longitudinal epidemiologic investigation. The 5-year follow-up examination was interrupted by a major earthquake, and examinations were resumed 2 weeks after the quake. Participants screened after the quake had, on average, higher heart rates, serum cholesterol, and triglycerides than participants examined before the quake; these differences were independent from the coronary heart disease risk factor values measured 5 years previously during the baseline examination. The data collected during the 12-year examination indicated that the observed short-term increase in serum lipids and heart rate was not present long-term (7 years after the quake). These longitudinal data indicate that exposure to a natural disaster can be associated with short-term increases in heart rate, serum cholesterol, and triglycerides but that there is no apparent long-term effect on these coronary heart disease risk factors.

OBJECTIVE:s To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. Design Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). Participants 303 020 people from the EPIC cohort (total 500 000) who had never smoked or who had stopped smoking for at least 10 years, 123 479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. MAIN OUTCOME MEASURES: Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. RESULTS: Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). CONCLUSIONS: This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.

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.