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Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02–1.86), P= 0.01, and 1.44 (95% CI 1.04–1.98), P= 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60–1.77), P= 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50–1.70), P= 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57–1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19–1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

Objectives To estimate the incidence and epidemiological profile of childhood (0–14 years) Hodgkin’s lymphoma in Greece derived by the network of childhood Hematology–Oncology departments on the basis of all 95 newly diagnosed cases during a seven-year period.

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: To assess serum adiponectin levels of neonates in relation to ponderal index and birth length with and without adjustment for potential confounding factors including maternal factors and perinatal characteristics. DESIGN: A cross-sectional study. METHODS: Three hundred and three newborns (Caucasian, singleton, full term, with a birth weight of >/=2500 g, and apparently healthy) were included in the study. Blood samples were collected from the newborns no later than the fifth day of life for measurements of adiponectin and major IGF system components (IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3)). The data were analyzed using simple and multiple regression analyses. RESULTS: Adiponectin is substantially higher in neonates than in adults, with no evidence of the gender dimorphism observed among adults. We found an inverse association between neonatal adiponectin levels and newborn ponderal index and a positive association with newborn length by univariate analysis. We also found a statistically significant inverse association of adiponectin with jaundice/bilirubin, and a marginally significant positive association of this hormone with IGFBP-3 but no significant association with any maternal factors. In multivariate analysis, the inverse association between serum adiponectin and ponderal index does not remain significant after adjustment for potential confounding factors. In contrast, neonatal adiponectin levels correlate inversely significantly and independently with liver maturity and IGF-II and tend to remain positively associated with IGFBP-3 and increased birth length. CONCLUSIONS: An inverse association of adiponectin with ponderal index by univariate analysis is not independent from confounding factors. In contrast, the positive association between serum adiponectin and birth length may reflect either a direct effect of adiponectin or an adiponectin-mediated increase in the sensitivity of tissues to insulin and components of the IGF system, and needs to be explored further.

Objective: To examine the role of six flavonoid classes (flavanones, flavan-3-ols, flavonols, flavones, anthocyanidins and isoflavones) and vitamin C in the aetiology of stomach cancer. Methods: Case–control study undertaken in Greece in the 1980s. Dietary information was obtained from 110 patients with incident stomach adenocarcinoma and 100 control patients. Flavonoid estimates were based on the recently released database of the US Department of Agriculture. Results: In models including sociodemographic variables, energy intake, vegetables, fruits and, alternatively, vitamin C the six flavonoid classes, only flavanones and vegetables remained significantly inversely associated with stomach cancer risk. The odds ratio (95% confidence intervals) per one standard deviation increase of intake of flavanones was 0.55 (0.31–0.96) whereas for vitamin C it was 1.05 (0.46–2.41). When fruits and vegetables were not adjusted for, both vitamin C and several flavonoid categories were inversely associated with stomach cancer risk, but these associations could be attributed to other compounds in these foods. Conclusions: Among the major flavonoid classes studied, only flavanone intake is inversely associated with stomach cancer risk and could account for the apparent protective effect of fruit intake against this form of cancer. Additional factors, however, are likely to be involved in the consistent protection conveyed by vegetables.

Chronic pulmonary diseases are a major cause of morbidity and mortality worldwide. The present study is a case–control study nested in a defined cohort, undertaken in Athens, Greece, in order to investigate the association between long-term exposure to ambient air pollution and the development of chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD). Individualized personal exposure assessment has been applied based on long-term residential and occupational subject history linked with geographical air pollution distribution. The first consecutive 3904 participants from the European Prospective Study into Cancer and Nutrition (EPIC), all residents of Athens, were asked to complete a questionnaire. One hundred and sixty-eight participants reporting a history of COPD symptomatology and 168 healthy controls recruited from the same study base individually matched for age and gender, were visited by a physician at their homes for conducting spirometry and a medical interview. Eighty-four of the 168 self-identified as cases were diagnosed as having chronic bronchitis, emphysema or COPD. Logistic regression models were used for statistical evaluation. Cases were more exposed to air pollution compared to controls. The estimated odds ratio (OR) indicates an increase of 37% in the risk of medically confirmed cases per exposure quartile (p= 0.02). When most of the subjects exposed are considered vs. all others, there is a twofold increase in disease risk (p= 0.03). Our findings provide evidence that long-term exposure to air pollution is an important factor in the development of chronic respiratory diseases.

AbstractThe European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35?70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrolment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case?control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

AbstractThe European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects? characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.

Objective: To depict the magnitude and spectrum of childhood injuries attributable to falls from bunk beds in comparison with conventional beds and to outline sociodemographic risk factors and injury characteristics. Study design: Case-control investigation. Setting: Accident and emergency departments of four hospitals in Greece, namely a teaching children's hospital and a trauma hospital in Greater Athens and the two district hospitals in the Magnesia county and the Corfu island. Patients: During the three year period 1996-98, 1881 children (0-14 years) presenting with bed fall injuries were recorded by the Emergency Department Injury Surveillance System (EDISS). Out of these, 197 children with falls from bunk beds served as cases and 1684 children with falls from conventional beds served as controls. Results: From the analysis and a nationwide extrapolation, it was calculated that each year about 5000 children in Greece (total population 10 million) seek medical attendance at an emergency department for a bed injury, corresponding to an estimated incidence of about 3 per 1000 children years. Out of bed fall injuries, 10.5% are from bunk beds, 10.4% from cribs, 3.1% from cots, and 76.0% from other conventional beds. Falls from the bed ladder accounted for 8% of all bunk bed injuries. Boys are at higher risk for falls from beds but there is no evidence that the proportion is different depending on the type of bed used. Relatively few falls from bunk beds are recorded outside the crowded apartments of Greater Athens or among migrant children. The increased relative risk of injuries from bunk bed falls during the sleeping hours indicates the higher risk of injury after a fall from a bunk rather than a conventional bed. Injuries from bunk bed falls are generally more serious than those from conventional bed falls (overrepresentation of brain injuries, fractures, multiple injuries, and injuries requiring hospitalisation). Overall, it can be estimated that almost half of the sleep related bunk bed injuries are easily preventable. Conclusions: Falls from bunk beds represent a non-negligible childhood injury risk. A sizeable fraction can be avoided with simple design modifications of the product, such as use of side rails in the upper bed or removal of the bed ladder when not in use.

Since sports participation entails the risk of injuries that account for substantial morbidity and disability, the existence of adequate epidemiological information is essential for the development of sound preventive strategies. In this study, we present data on the occurrence of sports injuries among children in six European countries, namely Austria, Denmark, France, Greece, The Netherlands, and the United Kingdom. An operational definition for sports injuries was developed, and comparable data from the European Home and Leisure Accident Surveillance System, an established injury surveillance system operating in 12 European union countries, were collected from the participating member states, during a 1-year period (1998). Sports injuries were examined in schools, in organised and unorganised settings, and in specific types of sports by demographics and injury descriptive variables. Sports injuries represent a quantitatively important and sufficiently serious problem in European union countries, accounting for an estimated annual number of about a quarter of a million outpatient visits in two of the participating countries, which provide national estimates. It is evident, that sport injuries are not only common but also injuries of considerable severity, since a large fraction represents fractures, while approximately 4% of the total require hospitalisation. Football and basketball among male children are, in declining order, the two sports responsible for the most frequent injuries in the European union countries, whereas gymnastics and volleyball prevail among females. The study indicates the importance of injury surveillance in describing the epidemiology of sports injuries and provides an estimate of the magnitude and the profile of sport injuries that take place annually in European union countries.

Objective To assess the effect(s) of transient events which are perceived as stressful on the inseption of preterm delivery.

Objective: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States. Methods: We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data. Results: The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer. Conclusion: The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

To study regionalized acute injury services on an island with high seasonal fluctuation of the population at risk.

Objectives: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC). Methods: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays. Results: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5–78.3) for the presence of HBsAg and 23.2 (11.4–47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9–216.6) compared to infection with neither virus. Conclusions: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.

The nutritional aetiology of prostate cancer was evaluated in Athens, Greece, through a case-control study that included 320 patients with histologically confirmed incident prostate cancer and 246 controls without history or symptomatology of benign prostatic hyperplasia or prostate cancer, treated in the same hospital as the cases for minor diseases or conditions. Among major food groups, milk and dairy products as well as added lipids were marginally positively associated with risk for prostate cancer. Among added lipids, seed oils were significantly and butter and margarine non-significantly positively associated with prostate cancer risk, whereas olive oil was unrelated to this risk. Cooked tomatoes and to a lesser extent raw tomatoes were inversely associated with the risk for prostate cancer. In analyses focusing on nutrients, rather than foods, polyunsaturated fats were positively and vitamin E inversely associated with prostate cancer. We conclude that several nutrition-related processes jointly contribute to prostate carcinogenesis. Int. J. Cancer 80:704–708, 1999. © 1999 Wiley-Liss, Inc.

ObjectivesHelmet use is the best preventive measure available against two wheel motorized vehicle (TWMV) related head injuries. In some countries, however, helmets are used only by a minority of TWMV riders. In collaboration with the Road Traffic Police Department, an inspection survey was undertaken to assess the prevalence and to determine predictors of helmet use.SettingThe Greater Athens area, Greece, during July and August 1998.MethodsA total of 982 TWMVs were stopped, 349 of which had two riders (36%). All riders were interviewed by staff members of the Centre for Research and Prevention of Injuries among the Young.ResultsThe average prevalence of helmet use was 20.2%. It ranged from 9.7% on small suburban roads to 50.8% on highways. Prevalence of use was significantly lower during the weekend days and at night. Women were significantly more likely to wear a helmet and, controlling for gender, drivers were significantly more likely to be helmet users. Riders of more powerful TWMVs and passengers, who themselves had a TWMV driving license, were helmet users more frequently. Among non-users, the majority (46%) indicated that "the helmet made them feel uncomfortable", particularly in warm weather, whereas 18% claimed that there was little need for a helmet in low speed riding.ConclusionsA multipronged campaign is urgently needed in Greece to increase the prevalence of helmet use by TWMV riders. The campaign should include not only police enforcement but also initiatives to make helmets more convenient to wear and less expensive.

Whereas most idiosyncratic environmental sensitivity complaints do not fit known diagnoses, the multiple chemical sensitivities syndrome (MCS) is an extreme presentation that has defined diagnostic criteria. MCS symptomatics claim that they acquired a sensitized state as the result of a chemical exposure, usually to a solvent or pesticide, but not to a fragrance. Before this exposure, they did not experience symptoms. Following sensitization, symptoms increasing in number and severity with time are attributed by the MCS symptomatic to various exposures that are innocuous to most individuals. Although phenomenological studies have provided no evidence that particular odors elicit MCS symptoms, low levels of fragrances and perfumes are frequently associated with the reporting of MCS symptoms. This evaluation examines proposed mechanisms by which odorants and fragrances might cause either sensitization or elicitation of MCS symptoms, including altered odor sensitivity, primary irritancy or irritancy-induced upper airway reactivity, neurogenic switching of trigeminal irritancy signals, time-dependent sensitization and limbic kindling, CNS toxicity, and various psychiatric conditions. In no case was there persuasive evidence that any olfactory mechanism involving fragrance underlies either induction of a sensitized state or the triggering of MCS symptoms. Fragrances and other odorants could, however, be associated with symptoms as claimed by MCS symptomatics, because they are recognizable stimuli, but fragrance has not been demonstrated to be causal in the usual sense.

ObjectivesTo investigate whether left handed children are at increased risk for injuries, particularly upper limb injuries.SettingAthens, Greece, during a six month period in 1995-96.MethodsCases were 129 children 4-14 years old with unintentional upper limb injuries from a population based injury database. Two control children matched for gender and age were selected from among those seen at the same medical institution for minor, non-injury ailments. On the basis of information provided by the children and their guardians, sociodemographic variables were recorded, hand preference was assessed, and each child's activity score was calculated through an abbreviated version of Achenbach's scale.ResultsLeft handed children have a moderately increased upper limb injury risk with a tendency of recurrence of this injury. The risk of upper limb injury is also raised among children of young fathers, whereas it appears to be inversely related to crowding index and activity score--three variables that were controlled for as potential confounders.ConclusionsThis study provides limited support for the hypothesis that left handed children are at increased risk for injury. The excess risk, if genuine, is likely to be limited to cultural settings in which right handedness is perceived as the norm.

Three malachite green dyes, Merck's concentrated for microscopy and bacteriology (old), Merck's malachite green oxalate (oxal), and Difco's malachite green, were used for preparation of 3 batches of Rappaport's medium. These media were tested for growth of 40 Salmonella serotypes and for inhibition of competing organisms. All Rappaport's media behaved similarly and supported excellent growth of 38 serotypes. When Salmonella cultures were diluted in fecal-saline suspensions and inoculated in all Rappaport media the competing organisms in these suspensions were efficiently inhibited. However, the inhibition of competing organisms was less efficient when Rappaport's media were inoculated with preenrichment cultures of 20 samples of minced meat in buffered peptone water. In this respect, Difco's malachite green was clearly inferior to the other two dyes. It is concluded that Merck's malachite green oxalate is as efficient as the old dye of the same brand which is no longer produced, and can replace it in the preparation of Rappaport's medium.

Résumé A l'occasion de l'entrée de la Grèce dans la Communauté Economique Européenne, les relations existant entre les taux de mortalité par cause et différents indices socio-économiques sont examinées. Les différences encore marquées existant au sein de la CEE concernant le niveau de vie et le rythme de développement industriel, le niveau d'urbanisation, le volume et la nature de la consommation individuelle sont mis en relation avec les taux de mortalité générale et spécifique. Parmi les facteurs étudiés, les variables de nutrition montrent une forte association avec la mortalité cancéreuse et coronarienne. Le niveau d'urbanisation de la population est lié à la mortalité cardio-vasculaire et par maladies respiratoires aiguës. Le type d'emploi et le produit intérieur brut (PIB) d'un pays sont associés à la mortalité par accidents, intoxications et maladies respiratoires.

Summary The incorporation of14C-thymidine by peripheral blood lymphocytes stimulated by phytohemagglutinin (PHA) and the proportion and absolute number of E-rosettes were determined in 28 prostitutes and the results were correlated with hepatitis B virus (HBV) serology. Women were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) as well as for antibody to the hepatitis B core antigen (anti-HBc). It was found that women who were carriers of HBsAg had significantly lower incorporation of14C-thymidine (median value 14451 counts per minute-cpm) compared to women positive for anti-HBc but negative for the other two markers (median value 28590 cpm) as well as to women negative for all the tested markers (median value 30600 cpm). No significant difference was found among the three groups studied with respect to either the absolute number or the percentage of E-rosettes. The results indicate that the presence of anti-HBc alone, is not related to the responsiveness of lymphocytes to PHA.

Summary The effect of the immunostimulant C. parvum on the establishment and course of mycoplasma arthritis of mice was investigated. Male Swiss albino mice were injected intra-venously with M. arthritidis culture and intraperitoneally with C. parvum. It was shown that mice immunostimulated with C. parvum were significantly protected against the establishment of arthritis if the mycoplasma was given 9 days after the immunostimulant. However, when the arthritis was established C. parvum had no effect on the course of the arthritis. A close association between mycoplasma arthritidis and synovial cells in proposed as a possible explanation of this observation.

The short-term effects of air pollution on morbidity in the Athens population were studied. Data were collected on the daily number of emergency outpatient visits and admissions for cardiac and respiratory causes (diagnoses at time of admission) to all major hospitals in the greater Athens area during 1988. Measurements of air pollution made by the Ministry of the Environment monitoring network included values for smoke, carbon monoxide, and nitrogen dioxide. Statistical analysis was done using multiple linear regression models controlling for potential confounding effects of meteorological and chronological variables, separately for winter (1/1-3/21 and 9/22-12/31) and summer (3/22-9/21). It was found that the daily number of emergency visits was related positively with the levels of air pollution, but this association did not reach the nominal level of statisical significance for most pollutants. The number of emergency admissions for cardiac and respiratory causes was related to a statistically significant degree with all indices of air pollution during the winter. Thus, the average adjusted increase in the daily number of cardiac admissions corresponding to an increase from the 5th to the 95th percentile of the season-specific distribution of each pollutant ranges from 15 to 17% or from 11 to 12.5 admissions per day, and for the daily number of respiratory admissions from 20 to 29% or from 8.3 to 12.1 admissions. The results of the present study indicate that air pollution in the Athens area has short-term effects on morbidity in the population.

To date, no study has attempted to correlate hormone levels between successive pregnancies in the same woman. Serum levels of total estradiol and total free estradiol have been measured between the eighth and the 17th weeks in the first and second full-term pregnancies of 34 white women participating in the Collaborative Perinatal Study, 1959-1965. Intraindividual interpregnancy Pearson's product moment correlations were calculated. Partial correlation coefficients (adjusted for gestational age) for log pregnancy total estradiol and total free estradiol were 0.78 and 0.73, respectively (p < 0.001). These findings provide evidence that levels of pregnancy estradiol are significantly and strongly correlated in successive pregnancies of the same woman. This phenomenon can provide an explanation for the higher concordance of breast cancer incidence between two sisters than between a mother and daughter in the familial pattern of breast cancer.

A case-control study concerning the association between diet and peripheral arterial occlusive disease was conducted in Athens, Greece. The case series consisted of 100 patients with this disease, whereas controls were 100 patients with conditions requiring minor surgical care who were admitted to the same teaching hospital. Diet was ascertained through a semiquantitative food frequency questionnaire. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month and summing these estimates for all food items. Data were analyzed using multiple logistic regression procedures, controlling for total energy intake by taking nutrient residuals and by using multivariate nutrient density models. Saturated fatty acids (odds ratio (OR) and 95% confidence interval (CI) contrasting the 75th centile (upper) with the 25th centile = 1.96 and 1.14-3.39), proteins (OR = 2.86, 95% CI 1.47-5.55), and dietary cholesterol (OR = 6.07, 95% CI 2.74-13.46) were associated with increased risk of peripheral arterial occlusive disease, whereas polyunsaturated fatty acids (OR = 0.48, 95% CI 0.24-0.93) and crude fiber (OR = 0.33, 95% CI 0.17-0.64) were related to reduced risk. Monounsaturated fatty acids and, by inference, olive oil occupy an intermediate neutral position between polyunsaturates and saturates (corresponding OR = 1.14, 95% CI 0.68-1.91). Higher intakes of fiber and vitamin C were associated with lower risk of peripheral arterial occlusive disease. The low occurrence of atherosclerotic diseases in Greece and other Mediterranean countries may be due to the substitution of olive oil in place of saturated fats and/or the consumption of a diet high in vegetables, fruits, and other fiber-containing foods.

A case‐control study focusing on the role of diet in the etiology of gastric cancer was undertaken in Piraeus, the sister city of Athens, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 110 consecutive patients with histologically confirmed adenocarcinoma of the stomach, admitted to two teaching hospitals during a 3‐year period; the control series consisted of orthopedic patients admitted to a nearby hospital for accidents, fractures and other orthopedic disorders, during the same time period. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of lemons, oranges, brown bread, and raw, salad‐type vegetables (particularly lettuce, onions and cucumbers) and, independently, significantly more frequent consumption of pasta, beans and nuts. A relative risk of about 40 was found between extreme quintiles when the above 9 food Items were combined in a linear risk score. Use of an index constructed from the study material will clearly overestimate the level of risk between the extreme quintiles, but nevertheless the risk differences appear noteworthy, and consistent with the international variation in the incidence of gastric cancer. No significant associations were found with alcoholic beverages, coffee or tea.

We evaluated the reproducibility and relative validity of a 190-item semi-quantitative food frequency questionnaire (FFQ) to be used in a large prospective study in the Athens area of Greece.

To investigate the effect of long term hashish use on T-lymphocytes we have measured the incorporation of14C-thymidine by peripheral blood lymphocytes, unstimulated and stimulated by phytohemagglutinin, as well as the proportion and number of E-rosettes in 12 healthy male chronic users of the drug before and after a smoking session, and in 15 control subjects.

The Environmental Health and Safety Council of the American Health Foundation has examined current estimates of cancer risks associated with the presence of asbestos-containing materials (ACM) in public buildings. The Council finds that even complete removal of asbestos from all of these buildings will provide no measurable benefit to public health. The removal of nonfriable ACM only can be postulated to protect the public against a small hypothetical risk that cannot be measured epidemiologically. Moreover, examination of the assumptions used in the risk assessment calculations leads to the conclusion that these small calculated risks are likely to represent overestimates. In recent surveys, the measured asbestos levels in indoor air cast some doubt on whether occupant exposure to asbestos levels are contributed to significantly by ACM even when some of the material is friable or in bad condition. Furthermore, the models used for cancer risk estimates assume no threshold level for cancer and conclude that any exposure is carcinogenic. This may be unjustified in light of information on the mechanisms for some asbestos-caused disease. Based on the best available data, it is very unlikely that cancer will result from indoor asbestos exposure, especially where ACM is well maintained.Copyright 1994, 1999 Academic Press, Inc.

This article reviews the epidemiology of cancer of the pancreas, both descriptive and analytical, at all times cognizant of the problems of misdiagnosis, particularly underdiagnosis, of this lethal disease that continue to hinder epidemiological studies. Pancreas cancer is consistently reported to occur more frequently in men than in women, in blacks than in whites, and in urban rather than rural population groups. In some countries, the mortality rates continue to rise, whereas in others, declining levels of disease can be seen among members of younger birth cohorts. Although some of these patterns can be explained by variation in pancreas cancer risk factors, many cannot. Analytical studies consistently demonstrate that cigaret smoking increases the risk of cancer of the pancreas, and this appears, at the present time, to be the only clearly demonstrated risk factor for pancreatic cancer. Although the association with disease risk and coffee consumption, alcohol consumption, occupational exposures, diabetes, pancreatitis, and other factors requires clarification, it appears likely that the most fruitful research area in the coming years may involve exploration of pancreatic cancer risk and nutritional practices.

Caesarean section rates have increased in Greece by almost 50% during the last 13 years. We conducted a study in Athens, Greece, to assess the importance of a series of medical and socioeconomic factors in the use of Caesarean section or operative vaginal procedures, rather than a non-operative process, for the delivery of singleton, liveborn babies of primiparous mothers. We used a case control approach to compare 444 babies delivered through a Caesarean section and 130 delivered through operative vaginal delivery with 1235 normally delivered babies in a public and a private hospital. Data were analysed through multiple logistic regression. Caesarean section was more commonly performed in older, shorter or overweight mothers and for high and low birth-weight babies, as well as in response to several obstetric complications and following in-vitro fertilization. A similar pattern was noted with respect to operative vaginal delivery, except that this procedure was not unusually frequent among overweight women and was not encountered in this study among children born after in-vitro fertilization. Caesarean section was performed twice as often in the public teaching hospital as in a private maternity hospital, and operative vaginal delivery was several times more common in the former than in the latter, after controlling for biomedical risk factors. The unequal distribution of operative delivery procedures between the public and the private hospital raises questions about the justification of their performance in a substantial fraction of deliveries, and indicates that social factors condition their use.

The purpose of this paper was to assess the effectiveness of anti-tobacco smoking legislation from 1948 onwards in reducing actual per capita tobacco consumption in the twelve countries of the European Economic Community (EEC). In order to undertake these assessments a score was assigned to every legislative measure, indicating the a priori likely impact of this measure on tobacco consumption. Two approaches were then utilized. In the first, it was found that the cumulative anti-tobacco legislative score correlates well in time with a reduction of tobacco consumption. In the second, cross-sectional data from the EEC countries and multiple regression modelling were used to estimate the elasticities of tobacco price, per capita income and cumulative anti-tobacco legislation score; it was found that legislation has an impact on tobacco consumption which, although considerably smaller than the corresponding impact of tobacco price levels, is nominally significant and potentially important. The evaluative approaches utilized in this paper are based on observational data of ecologic nature and can provide only weak evidence about the causal nature of the reported associations. Nevertheless, this limited evidence suggests that legislative measures may be effective both by affecting price levels and through other mechanisms, including health education and the formation of a more general anti-smoking ethos.

Recent research suggests that intrauterine exposures, perhaps factors that influence birth weight and other indicators of fetal growth, may affect future breast cancer risk. Because birth weight shows seasonal variation in Sweden, we assessed whether risk for breast cancer is associated with month of birth. The analyses included all 115,670 women, born between 1858 and 1968, who were reported to the Swedish Cancer Registry in 1958-89 as having breast cancer. Poisson regression models were used to examine the data. After adjustment for seasonality of number of live births in the population at risk, a significant seasonal pattern was identified for women born between 1880 and 1920. Women born in June had a 5% higher risk of breast cancer than those born in December. By contrast, there was no evidence of birth seasonality among 440,948 women with cancer at other sites. Exposures relevant to breast cancer risk later in life are unlikely to be related to month of birth. Thus, prenatal or early post-natal factors influence breast carcinogenesis, but the seasonal variation in these factors must have decreased over time.

The Greek diet is characterized by a high total fat but low saturated fat intake. In a hospital-based case-control study of female breast cancer conducted in Athens (1989-91), 820 patients with confirmed cancer of the breast were compared with 795 orthopaedic patient controls and 753 hospital visitor controls, matched to the cases by age and interviewer. Diet was ascertained through a semiquantitative food frequency questionnaire; macronutrient intakes were estimated from the nutrient content of a selected typical portion size for each specified food item, summed for all items. Logistic regression was used to analyse the data, controlling for demographic and reproductive risk factors for breast cancer as well as for total energy intake and mutual confounding influences among nutrients. There was no significant or suggestive association of total protein, total fat, categories of fat or total carbohydrates with breast cancer risk. Thus, the mutually adjusted relative risk per quintile and (in parenthesis) 95% confidence interval were: for protein, 1.06 (0.94-1.20); saturated fat, 0.99 (0.89-1.11); monounsaturated fat, 0.97 (0.88-1.07), polyunsaturated fat, 1.05 (0.97-1.13); and total carbohydrates, 1.03 (0.94-1.12). In alternative analytical approaches only total protein appeared to be positively associated to the occurrence of breast cancer with some consistency, but the results were far from statistically significant. These findings do not support a role for fat or other energy-generating nutrients in the aetiology of breast cancer.

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.