[Show abstract][Hide abstract] ABSTRACT: It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
[Show abstract][Hide abstract] ABSTRACT: Fifty-one women with lung cancer and 163 other hospital patients were interviewed regarding the smoking habits of themselves and their husbands. Forty of the lung cancer cases and 149 of the other patients were non-smokers. Among the non-smoking women there was a statistically significant difference between the cancer cases and the other patients with respect to their husbands' smoking habits. Estimates of the relative risk of lung cancer associated with having a husband who smokes were 2.4 for a smoker of less than one pack and 3.4 for women whose husbands smoked more than one pack of cigarettes per day. The limitations of the data are examined; it is evident that further investigation of this issue is warranted.
International Journal of Cancer 07/2006; 27(1):1 - 4. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dietary intake of flavonoids has been reported to protect against coronary heart disease (CHD) risk, but associations of specific classes of flavonoids with CHD have not been adequately studied.
Hospital-based case-control study relying on interviewer administered questionnaires.
Cardiology Department of the University of Athens Medical School in the Hippokrateion General Hospital (1990-1991).
Cases were 329 patients with electrocardiographically confirmed first coronary infarct or a first positive coronary arteriogram, or both (participation fraction 93%). Controls were 570 patients admitted to the same hospital for minor conditions unrelated to nutrition (participation fraction 95%). All cases and controls were interviewed in the hospital wards by experienced interviewers, and a 110-item food frequency questionnaire was administered.
There was statistically significant evidence (P approximately 0.03) for an inverse association between intake of flavan-3-ols and CHD risk, an increase of about 21 mg per day corresponding to a 24% decrease in CHD risk. The inverse association between flavan-3-ols and CHD risk was largely accounted for by the intake of wine and to a lesser extent tea. For none of the other flavonoid classes was there statistically significant evidence of an association.
Flavan-3-ols, which are largely found in wine and tea, are inversely associated with, and may be protective against, coronary heart disease.
European Journal of Clinical Nutrition 01/2005; 58(12):1643-8. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Pollution Effects on Asthmatic Children in Europe (PEACE) study is a multicentre study of the acute effects of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphur dioxide (SO2) and nitrogen dioxide (NO2) on the respiratory health of children with chronic respiratory symptoms. The study was conducted in the winter of 1993/1994 by 14 research centres in Europe. A total of 2,010 children, divided over 28 panels in urban and suburban locations, was followed for at least 2 months. Exposure to air pollution was monitored on a daily basis. Health status was monitored by daily peak expiratory flow (PEF) measurements and a symptom diary. The association between respiratory health and air pollution levels was calculated with time series analysis. Combined effect estimates of air pollution on PEF or the daily prevalence of respiratory symptoms and bronchodilator use were calculated from the panel-specific effect estimates. Fixed effect models were used and, in cases of heterogeneity, random effect models. No clear associations between PM10, BS, SO2 or NO2 and morning PEF, evening PEF, prevalence of respiratory symptoms or bronchodilator use could be detected. Only previous day PM10 was negatively associated with evening PEF, but only in locations where BS was high compared to PM10 concentrations. There were no consistent differences in effect estimates between subgroups based on urban versus suburban, geographical location or mean levels of PM10, BS, SO2 and NO2. The lack of association could not be attributed to a lack of statistical power, low levels of exposure or incorrect trend specifications. In conclusion, the PEACE project did not show effects of particles with a 50% cut-off aerodynamic diameter of 10 microm, black smoke, sulphur dioxide or nitrogen dioxide on morning or evening peak expiratory flow or the daily prevalence of respiratory symptoms and bronchodilator use.
European Respiratory Journal 01/1999; 12(6):1354-61. · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have undertaken an autopsy-based study to evaluate the etiologic importance of active and passive smoking, as well as socio-demographic variables, in the development of pathologic precursors of lung cancer. Lung specimens were taken at autopsy from 531 persons who had died within four hours from a cause other than respiratory or cancer in Athens (Greece) or the surrounding area. Specimens were examined blindly for basal cell hyperplasia, squamous cell metaplasia, cell atypia and mucous cell metaplasia, i.e., pathological entities considered as epithelial, possibly precancerous, lesions (EPPL). Interviews were conducted with next of kin of the deceased. Suitable autopsy specimens as well as completed interviews were eventually available for 275 subjects. EPPL score was regressed on the available independent variables. EPPL score was higher among active smokers than among nonsmokers, while ex-smokers occupied an intermediate position. Conditional on smoking habits, EPPL score was higher among women than among men and higher among manual than among non-manual workers, in agreement with the corresponding patterns with respect to lung cancer. Nonsmoking women married to ever smokers had significantly higher EPPL score than those married to never smokers. The overall findings of this study suggest that EPPL is a valuable indicator of lung cancer risk and that exposure to environmental tobacco smoke is associated with higher EPPL levels and therefore with higher lung cancer risk.
Scandinavian journal of social medicine 01/1997; 24(4):259-63.
[Show abstract][Hide abstract] ABSTRACT: In a hospital-based case-control study of endometrial cancer undertaken in Athens (1992-94), 145 women residents of Greater Athens with confirmed cancer of the endometrium were compared with 298 control patients with orthopaedic diseases. Personal interviews were conducted in the hospital setting, and diet was assessed using a validated semiquantitative food frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient intake of a typical portion size for each specified food item by the frequency at which the food was consumed per month and summing these estimates for all food items. Data were modelled through logistic regression, controlling for demographic, reproductive and somatometric risk factors for endometrial cancer as well as for total energy intake. No macronutrient was significantly associated with endometrial cancer risk, but increasing intake of monounsaturated fat, mostly olive oil, by about one standard deviation was associated with a 26% risk reduction (odds ratio = 0.74; 95% confidence interval 0.54-1.3). Among micronutrients, only calcium intake was significantly inversely associated with endometrial cancer risk, whereas there was evidence against retinol and zinc imparting protection against the disease. With respect to food groups, there was weak and non-significant evidence that vegetables are protective, whereas consumption of pulses was positively associated with disease possibly because they contribute substantially in Greece to energy intake in excess of physical activity-dependent requirements.
British Journal of Cancer 06/1996; 73(10):1284-90. · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A hospital-based case-control study of cancer of the endometrium was conducted in Athens, Greece, from 1992 to 1994. The cases were 145 women residents of Greater Athens with histologically confirmed incident cancer of the endometrium, operated in the two cancer hospitals of the Greater Athens area or the major University Department of Obstetrics and Gynecology. Controls were 298 women residents of Greater Athens hospitalized for bone fractures or other orthopedic conditions in the accident hospital of Greater Athens. The data were analyzed by modeling through multiple logistic regression. The risk of endometrial cancer decreased with the number of livebirths (p for trend < 0.01), with early age at menopause (p = 0.03), and with later age at menarche (p = 0.11), whereas miscarriages and induced abortions were clearly unrelated. There were nonsignificant relations of disease risk with smoking (inverse), alcohol (inverse), and menopausal estrogens (positive), whereas oral contraceptive use was too uncommon to allow meaningful study. The lower risk of the disease associated with current occupations requiring manual activity (p = 0.03) and the lower, although not significantly so (p = 0.36), energy intake of cases in comparison to controls suggest that physical inactivity could be an important risk factor for endometrial cancer. Women with endometrial cancer were significantly taller than control women (p = 0.02). The latter results indicate that excess energy intake in early life, leading to higher attained stature, and excessive energy intake in later life, on account of physical inactivity and leading to higher body weight, converge in increasing the risk for endometrial cancer.
[Show abstract][Hide abstract] ABSTRACT: We conducted a case-control study in Athens, Greece, between January 1990 and April 1991 to examine the association between diet and coronary heart disease. The case series comprised 329 patients with electrocardiographically confirmed first coronary infarct or a first positive coronary arteriogram, or both, who were admitted to a major teaching hospital during a 16-month period. Controls were 570 patients admitted to the same hospital for minor conditions believed to be unrelated to nutrition. Total energy intake was inversely associated with coronary heart disease risk, a quintile energy increase corresponding to a relative risk of 0.96. After controlling for total energy intake, dietary fat was positively related to coronary heart disease, and total carbohydrates were negatively related to coronary heart disease, the nutrient-specific relative risks for a quintile increase being 1.19 (95% confidence interval = 0.96-1.48) and 0.81 (95% confidence interval = 0.67-0.97), respectively. Major fat components (saturated, monounsaturated, and polyunsaturated fat) did not appear to have differential risk implications for coronary heart disease; however, cooking with margarine was associated with an increased relative risk (1.87; 95% confidence interval = 0.82-4.28). Dietary proteins, cholesterol, and vitamin C were not associated with coronary heart disease.
[Show abstract][Hide abstract] ABSTRACT: We conducted a case-control study in Athens, Greece, bepositively related to coronary heart disease, and total carbo-tween January 1990 and April 1991 to examine the associa-hydrates were negatively related to coronary heart disease, tion between diet and coronary heart disease. The case seriesthe nutrient-specific relative risks for a quintile increase being comprised 329 patients with electrocardiographically con1.19 (95% confidence interval = 0.96-1.48) and 0.81 (95% confidence interval = 0.96-1.48) and 0.81 (95% confidence interval =-0.67-0 97),-respectively.-Major fat components (saturated, monounsaturated, and polyunsaturated fat) did not appear to have differential risk implications for coronary heart disease; however, cooking with margarine was associated with an increased relative risk (1.87; 95% confidence interval = 0.82-4.28). Dietary proteins, cholesterol, and vitamin C were not associated with coronary heart disease. (Epidemiology 1993, 4:511-516)
(C) Lippincott-Raven Publishers.
[Show abstract][Hide abstract] ABSTRACT: In Reply.
—Mr Mantel is concerned about the misclassification issue. It has been argued that some women with lung cancer who were or have been smokers may have intentionally denied (because of guilt or social pressures) this fact. It is difficult to imagine that such a bias could operate in the context of an autopsy study. Furthermore, in this study, the outcome variable is semiquantitative and odds ratios cannot be interpreted as estimates of RR for lung cancer. Mantel does not point out any bias, nor does he consider any issue that we did not ourselves discuss in the "Comment" section of our article; he simply indicates that he disagrees with our conclusions.
JAMA The Journal of the American Medical Association 10/1993; 270(14):1691-1691. · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim was to determine whether induced abortions could increase the risk of secondary infertility.
This was a case-control study; cases were women with secondary infertility, individually matched to two controls who were currently pregnant. Each participant was interviewed by one of two medical doctors using a questionnaire that sought information on their demographic, socioeconomic, medical, and reproductive status. The data were analysed by conditional logistic regression.
The study took place in the Alexandra Maternity Hospital in Athens, Greece, in 1987-88.
84 women consecutively admitted with secondary infertility and 168 pregnant controls took part.
Eight cases and no controls reported a previous ectopic pregnancy, confirming that the occurrence of a pregnancy of this type dramatically increases the risk of secondary infertility. Furthermore, the occurrence of either induced abortions or spontaneous abortions independently and significantly increased the risk of subsequent development of secondary infertility. The logistic regression adjusted relative risks (and 95% confidence intervals) for secondary infertility were 2.1 (1.1-4.0) when there was one previous induced abortion and 2.3 (1.0-5.3) when there were two previous induced abortions. Tobacco smoking significantly increased the risk of secondary infertility, the adjusted relative risk being 3.0 (1.3-6.8).
Legalised induced abortions, as currently practised in Greece, appear to increase slightly the relative risk of secondary infertility.
Journal of Epidemiology & Community Health 03/1993; 47(1):36-9. · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case-control study of coronary heart disease (CHD) was conducted in Athens, Greece. The case series consisted of 329 patients with electrocardiographically confirmed coronary infarct or a diagnostic coronary arteriogram, or both, who were admitted during a 16-month period to a major teaching hospital. Controls were 570 patients admitted to the same hospital just before or after the CHD cases for minor surgery; eye, ear, nose or minor urological problems; or chest problems definitely shown to be unrelated to CHD. All cases and controls were interviewed in the hospital wards and selected laboratory data were abstracted. The main analysis was done by modelling through multiple logistic regression, controlling for demographic variables as well as for the mutual confounding effects of the investigated risk factors. Obesity, hypertension, diabetes mellitus, elevated blood cholesterol and excessive coffee intake were significant (P < 0.02) independent risk factors with relative risk estimates in the 2- to 3-fold range. Non-significant positive associations were found with respect to tobacco smoking and modest coffee consumption, whereas non-significant negative associations were noted with respect to alcohol intake and regular exercise. A negative association with duration of afternoon siesta was of borderline statistical significance.
International Journal of Epidemiology 12/1992; 21(6):1074-80. · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between involuntary smoking and lung cancer has been supported by most epidemiologic studies, but a number of authors and interest groups claim that the possibility of bias has not been excluded. Few autopsy-based studies have explored the role of active smoking and other exposures in lung carcinogenesis, and none has been previously done to examine the role of passive smoking. We have undertaken such an autopsy-based study in Athens, Greece.
Lung specimens were taken at autopsy from 400 persons 35 years of age or older, of both genders, who had died within 4 hours from a cause other than respiratory or cancer in Athens or the surrounding area. For each person at least seven tissue blocks were taken from the main and lobar bronchi and at least five blocks from the parenchyma, including an average of about 20 smaller cartilaginous bronchi and membranous bronchioles. The specimens were examined without knowledge of the exposures of the particular subject in Turin, Italy. For 283 (71%) of the subjects the preservation of the bronchial epithelium was satisfactory for pathological examination, and for 206 among them (73%) an interview could be arranged with their next of kin, focusing on smoking habits of the deceased and their spouses, as well as other variables. The interviewers were not aware of the results of the pathological examinations.
Specimens were examined for basal cell hyperplasia, squamous cell metaplasia, cell atypia, and (in membranous bronchioles and bronchiolo-alveolar airways) mucous cell metaplasia, ie, pathological entities that may be lung cancer risk indicators or epithelial, possibly precancerous, lesions (EPPL). The gland and wall thicknesses were also measured and their ratio calculated (Reid Index).
In comparison with nonsmokers, EPPL values were significantly higher among current smokers and higher, but not significantly so, among former smokers. Furthermore, EPPL values were significantly higher among deceased nonsmoking women married to smokers rather than to nonsmokers. In this set of data neither occupation nor residence was associated with EPPL, but this could be due to the poor correlation of residential history with exposure to air pollution and the lack of adequate standardization of contemporary Greek occupations. The Reid Index was higher among smokers and former smokers in comparison with nonsmokers, among subjects with mainly urban residence in comparison with those with mainly rural residence, and among nonsmoking women married to smokers in comparison with those married to nonsmokers, but none of these differences was statistically significant.
These results provide support to the body of evidence linking passive smoking to lung cancer, even though they are based on a study methodologically different from those that have previously examined this association.
JAMA The Journal of the American Medical Association 11/1992; 268(13):1697-701. · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case-control study exploring the role of smoking and outdoor air pollution in the causation of lung cancer, by histologic type, in nonsmoking women, was undertaken in Athens between 1987 and 1989.
One hundred one women with lung cancer and 89 comparison women with fractures or other orthopedic conditions, all permanent residents of Greater Athens, were included in the study. Smoking habits were ascertained through interviews, whereas lifetime exposure to air pollution was assessed by linking blindly lifelong residential and employment addresses of all subjects with objectively estimated or presumed air pollution levels.
The age-adjusted relative risk and 95% confidence intervals for lung cancer among current smokers compared with nonsmokers was 3.40 (1.75-6.61); it was 7.43 (2.88-19.13) among those smoking for more than 30 years and 7.46 (2.40-23.17) among those smoking more than 20 cigarettes per day. The age-adjusted relative risk was 1.70 (0.75-3.89) for adenocarcinoma and 6.45 (2.73-15.25) for other histologic types of lung cancer; statistically significant dose-response trends were evident for both histologic groups. Air pollution levels were associated with increased risk for lung cancer but the relative risk was small and statistically not significant. However, when both air pollution and duration (or quantity) of tobacco smoking, as well as their interaction, were introduced in a multiple logistic regression model, the interaction term was significant at the suggestive level of 0.10.
Whereas there is no effect of air pollution among nonsmokers, the relative risk contrasting extreme quartiles of air pollution among smokers of 30 years duration was 2.23. The interaction was almost exclusively accounted for by the nonadenocarcinoma lung tumors.
Preventive Medicine 04/1991; 20(2):271-8. · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case-control study of the role of induced abortion and other factors on the subsequent occurrence of ectopic pregnancy was undertaken in 1986-1987 in Athens, Greece, where a similar study 20 years ago found a tenfold risk of ectopic pregnancy among women with one or more illegal induced abortions. Seventy women residents of Athens, consecutively admitted to the major state maternity hospital with a diagnosis of ectopic pregnancy, were individually matched with women with a newly diagnosed pregnancy of the same order as the ectopic index pregnancy. Two control women were found for each of 63 cases, but only one control for each of the remaining seven cases. All cases and controls were interviewed by the same qualified obstetrician. Statistical analysis was undertaken with stratification of individual matched triplets and pairs, as well as through conditional multiple regression procedures. The relative risk of recurrence of an ectopic pregnancy was 6.39 with 95% confidence interval (CI) 1.96-21.04. Miscarriages did not increase the risk of ectopic pregnancy. The relative risk for subsequent ectopic pregnancy among women with one or more induced abortion, compared to women without such abortions, was 1.87 (CI 0.84-4.16) controlling only for the matching factors, and 1.71 (CI 0.69-4.27) when marital status (a possible selection factor) was also accounted for in the conditional logistic regression. There was no evidence for increasing risk with increasing number of induced abortions. Past use of an intrauterine device (IUCD) was associated with a relative risk of 3.89 (0.72-21.02); the relative risk increased with the duration of use of the IUCD.(ABSTRACT TRUNCATED AT 250 WORDS)
British Journal of Obstetrics and Gynaecology 03/1991; 98(2):207-13.
[Show abstract][Hide abstract] ABSTRACT: Lung specimens were taken at autopsy from 214 subjects aged 35 years and over who had died from nonpulmonary causes in Athens or the surrounding countryside. The samples were coded and examined for entities thought to be linked to environmental exposures, reflecting epithelial, possibly precancerous, lesions, as well as for morphological features, which were summarized using Reid's index. Of the 214 specimens, 142 were suitable for pathological examination. Next-of-kin of 101 of the dead people were identified and asked about the subject's exposure to active smoking, passive smoking, possible occupational hazards, dietary factors and proxy indicators of air pollution (residence). Preliminary analysis, controlling for age and sex, indicates that active smoking is related, although not statistically significantly, to both the Reid index (difference, 0.28, corresponding to a one-tailed p value of 0.07) and epithelial, possibly precancerous lesions (difference, 16.7, corresponding to a one-tailed p value of 0.09). Nonsignificant differences were found in the preliminary analysis of this ongoing study with respect to the other environmental factors examined.
[Show abstract][Hide abstract] ABSTRACT: The aim was to investigate the reported association between air pollution and cause specific mortality in the city of Athens.
Cause specific mortality was contrasted between 199 d with high values of air pollution and 2*199 comparison days with low pollution, matched in a 1:2 ratio on the basis of various confounding factors. Statistical analysis was done, taking matching into account, using analysis of variance for randomised blocks.
The study was confined to the city of Athens, using data obtained between 1975 and 1982.
Cause of death was assessed in all 25 138 persons dying in the 3*199 d studied.
Causes of death were evaluated blindly by two medically qualified investigators on the basis of information in the death certificates. Mortality was generally higher during the high pollution days but the difference was more pronounced and more significant for respiratory conditions, even though the number of deaths in this category was smaller than the corresponding numbers in the other two categories examined (cardiac and "other" deaths).
The results show that the short term association between air pollution and overall mortality in Athens is likely to be causal, since it is particularly evident with respect to respiratory conditions, for which a biological air pollution link is more plausible.
Journal of Epidemiology & Community Health 01/1991; 44(4):321-4. · 3.29 Impact Factor