Tobacco smoking, coffee drinking, and occupation as risk factors for bladder cancer in Greece.

Patients with bladder cancer (250 males and 50 females), consecutively admitted during a 2-year period in the major cancer hospital of Athens, and an equal number of age- and gender-matched comparison patients with orthopedic conditions were interviewed regarding demographic, socioeconomic, and biomedical characteristics, including their occupations and their use of coffee and tobacco prior to the onset of their present disease or condition. Analyses of the data showed that cigarette smoking is an important, statistically significant and dose-dependent risk factor for bladder cancer, particularly in males (tobacco smoking is rare among older Greek women); drinking 2 or more cups of Greek coffee per day appears to be a risk factor for bladder cancer, independent of tobacco smoking, although the association is neither strong nor dose dependent; and a priori specified "high-risk" occupations were associated with an increased rate ratio for bladder cancer among men less than 65 years and among women in general but not among older men. The overall results of this study indicate that the established risk factors for bladder cancer in the United States and in other developed countries are, apparently, equally important for bladder cancer in Greece, despite the differences in composition and conditions of use of Oriental tobacco and Greek coffee and in the activities and exposures to carcinogens in the Greek work place.

Association between hepatitis C virus and hepatocellular carcinoma using assays based on structural and nonstructural hepatitis C virus peptides.

Stored sera from 181 Greek patients with hepatocellular carcinoma (HCC), 35 patients with metastatic liver cancer, and 416 hospital controls with diagnoses other than malignant neoplasm or liver disease were examined with first and second generation hepatitis C virus (HCV) enzyme immunoassays as well as with five HCV supplemental assays based on structural and nonstructural HCV peptides. Second generation HCV enzyme immunoassays were more sensitive than first generation assays. However, both assays had suboptimal specificity using the standard reactivity criterion (absorbance of sample to cutoff greater than or equal to 1.0). Specificity was improved by centrifugation and by using a sample's optical density to cutoff ratio greater than or equal to 3.0 or supplemental assays; in this instance the prevalence of antibodies to HCV was 13.3% (24 of 181), 0 (0 of 35), and 1.4% (6 of 416) in HCC, metastatic liver cancer, and hospital controls, respectively. A similar estimation of prevalence of antibody to HCV in HCC (12.5% or 4 of 32) was obtained when the recombinant immunoblot assay, second generation, was used to screen a random sample of HCC patients. The relative risk linking HCV to HCC was estimated as 10.4 (95% confidence interval, 4.2-26.0; P less than 0.0001). These data suggest that the prevalence of antibodies to HCV in HCC using stored sera has been previously overestimated even though the evidence of a causal association of HCV with HCC persists.

Absence of an association between past infection with hepatitis A virus and primary hepatocellular carcinoma.

Serum samples from 77 caucasians of Greek origin with primary hepatocellular carcinoma (PHC) and 77 age- and sex-matched controls were tested for antibody to the hepatitis A virus (anti-HAV). Anti-HAV was detected in 63 patients with PHC (82%) and in 70 controls (91%). These data suggest that past infection with hepatitis A virus is not related to the development of PHC, in marked contrast to the strong association between PHC and HBV.

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece.

The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research.

Liveborn children and risk of hepatocellular carcinoma.

Clinical, animal, and epidemiologic evidence indicates that exogenous steroids influence the risk of hepatocellular carcinoma (HCC) and a recent study suggested that parity also may increase the risk of this tumor in women. The latter hypothesis was evaluated in the data from a case-control study which was carried out in Athens and covered 166 male and 19 female cases of HCC, and 381 male and 51 female hospital controls. Among males, there was no association between the number of liveborn children and risk of HCC, whereas among women, there was a suggestive positive association. Compared with women with one or two children, the relative risk for HCC was 0.6 among nulliparous women, 1.3 among those with three or four children and 1.7 among those with five or more children. The association of parity with risk of HCC was limited to women who were positive for hepatitis-B surface antigen (HBsAg) and was not confounded by hepatitis-C virus infection or tobacco smoking. The small number of HCC cases does not permit firm conclusions. If confirmed, however, these results would provide the foundation for a practical preventive advice that could be given to women who are positive for HBsAg.

Total cholesterol and HDL-cholesterol in relation to socioeconomic status in a sample of 11,645 Greek adults: the EPIC study in Greece. European Prospective Investigation into Nutrition and Cancer.

OBJECTIVE: To examine the relationship between educational level, a powerful indicator of socioeconomic status in Greece, total cholesterol and HDL-cholesterol in a large sample of Greek adults. METHODS: The study sample consisted of 11,645 subjects, 4,398 men and 7,247 women, aged 23-86 years, who voluntarily participated in the Greek component of the EPIC study during 1994-98. Educational attainment was divided into low, medium, and high. Linear regression analyses were performed, in men and women separately, using total and HDL-cholesterol as dependent variables and educational level as independent, while controlling for age. RESULTS: Total blood cholesterol values are inversely associated with educational level in both genders, a pattern contrasting with that found 20 years ago. The association is more prominent among women. HDL-cholesterol values are inversely associated with educational level in men, whereas the association is less consistent in women.

Adolescents in high-risk trajectory: clustering of risky behavior and the origins of socioeconomic health differentials.

BACKGROUND: We have evaluated high-risk behavior of adolescents 12 to 17 years of age on the basis of seven binomial psychosocial variables in order to assess whether there is a tendency of these variables to cluster in the same individuals and to identify socioeconomic covariates of risky behavior. METHODS: Study participants were 547 adolescents from four high schools in Greece: two in rural areas, one in an upper-medium socioeconomic class areas, and one in a low-to-medium socioeconomic class area of Athens. Clustering was assessed by evaluating concordance of high-risk attributes examined in pairs, and was expressed as a series of odds ratios (ORs) as well as by factor analysis. RESULTS: All but one OR were higher than the null value, but they were particularly high with respect to smoking and nonuse of safety belts (OR = 3.2, P < 10(-4)), smoking and binge drinking (OR = 3.3, P < 10(-4)), smoking and riding with a drunk driver (OR = 5.3, P = 10(-4)), smoking and driving under the influence of alcohol (OR = 9.7, P < 10(-4)), nonuse of oral contraceptives and riding a car with a drunk driver (OR = 15.4, P = 0.002), and driving under the influence of alcohol and riding with a drunk driver (OR = 18.6, P < 10(-4)). Factor analysis indicated that risky behavior could be explained in terms of two component factors, namely carelessness in the context of self interest and irresponsible sexual behavior. A composite index integrating information of all seven high-risk indicators regressed on sociodemographic characteristics showed that risky behavior increased sharply with age and was concentrated strongly in the low-education families and the lower income areas. CONCLUSIONS: Several aspects of high-risk behavior tend to aggregate in the same individuals, and the clustering pattern has already been developed by late adolescence, mostly among the less privileged families and population groups. It appears that socioeconomic class health differentials may have strong roots in late adolescence.

Alpha 1-antitrypsin and survival in hepatocellular carcinoma.

The association between serum levels of alpha 1-antitrypsin (alpha 1 AT) at the time of diagnosis and survival was studied in a group of 78 patients with confirmed hepatocellular carcinoma (HCC). All 78 patients were followed until the time of death, which occurred in all instances from HCC, with a median time of 6 months and a range of 1-117 months. Cox's proportional hazards model was utilised in the analysis controlling for sex, age, HBsAg status and logarithmically transformed values of alpha-fetoprotein (alpha-FP). Older patients and patients positive for HBsAg have suggestively higher fatality rates (0.05 less than P less than 0.10) whereas in these data sex and AFP levels were not important prognostic factors. Increased levels of serum at alpha 1AT at the time of diagnosis of HCC were statistically significantly (P less than 0.05) related with shorter survival, patients with higher serum alpha 1AT by 200 mg 100 ml-1 having an expected survival time shorter by about 25%.

Urban living, tobacco smoking, and chronic obstructive pulmonary disease: a study in Athens.

We studied the relation of urban living and tobacco smoking to the development of chronic obstructive pulmonary disease. The study was based on 110 incident cases of chronic obstructive pulmonary disease between 50 and 60 years of age who were permanent residents of Athens and 400 control patients hospitalized for traumatic and orthopedic conditions in the same hospitals at the same time. All subjects were interviewed about their smoking habits, place of birth, history of past residence, and years of schooling. We found that subjects with more education have a reduced risk of developing chronic obstructive pulmonary disease, with 4 additional years of schooling corresponding to a 30% reduction of risk. We also found that those who have lived all their lives in urban areas (mostly in Athens) have a twofold greater risk of chronic obstructive pulmonary disease compared with people who have lived exclusively or partly in rural areas before settling in Athens. Finally, we found that smokers have a 10-fold relative risk of developing chronic obstructive pulmonary disease, and this risk is strongly dependent on the number of cigarettes consumed per day. The findings of the present study suggest that air pollution, or another aspect of the urban environment, can be an important contributor to the development of chronic obstructive pulmonary disease.

Salmonella isolation with Rappaport's enrichment medium of different compositions.

One hundred samples of feces of normal pigs were examined for the presence of salmonellae. The feces were pre-enriched for 18 h in peptone water and then, 0.1 ml of the pre-enrichment medium was inoculated in 10 ml of the original Rappaport medium (R30), and two modifications (R25 and R10) of this medium. Two of the broths (R30 and R25) were incubated at 37 degrees C (R30/37 degrees C and R25/37 degrees C) while the R10 medium was incubated at 43 degrees C (R10/43 degrees C). In addition 100 ml of R10 medium (R10/100 ml/43 degrees C) and 100 ml of the standardized Muller Kauffmann's tetrathionate broth (MK/100 ml/43 degrees C) (Edel and Kampelmacher, 1969) were inoculated with 1 ml and 10 ml, respectively, of the pre-enrichment medium, and incubated at 43 degrees C. With the method R10/100 ml/43 degrees C, 37 samples were found positive while with the method MK/100 ml/43 degrees C only 22 positive samples were detected (P less than 0.001). With the Rappaport media in 10 ml volumes, the modification R10 yielded 26 positive samples, while the R30 and R25 broths yielded only 15 and 19 positive samples. All Rappaport procedures had a much stronger inhibition of the competing organisms, particularly those giving Salmonella-like colonies (lactose and sucrose negative), than the MK/100 ml/43 degrees C method, a fact of considerable importance in everyday's practice.

Syphilis and gonorrhea; epidemiology update.

The epidemiologic patterns of venereal diseases (VD) in Greece were studied using data from the National Statistical Service, the University Hospital for VD and the special clinic for VD of the Ministry of Health, where prostitutes and homosexuals are examined. The main findings are as follows. Between 1962 and 1976 the frequency of both syphilis and gonorrhea declined among men as well as among women but the decline was more evident among women and among the older age groups (20+). Among men, the highest incidence is the age group 20-29 years, whereas among women the peak incidence is a little earlier. The rates for both syphilis and gonorrhea are higher in men than in women, higher in the greater Athens area than in the rest of Greece, and higher in single persons than in married one. There was a marked seasonal variation of VD with peak incidence at late summer. The decline of VD was also evident among prostitutes and male homosexuals with the exception of syphilis among uncontrolled prostitutes (increase) and male homosexuals (slight decrease).

Epidemiologic characteristics and trace elements in pancreatic cancer in Greece.

Epidemiologic characteristics were studied in a sample of 50 patients with pancreatic cancer admitted at various hospitals of Athens during an 18-month period, and in 206 controls hospitalized during the same period with diagnoses other than cancer, and disorders of liver or pancreas. Trace elements (Cu, Zn, Mg) were determined in all cancer cases and in 63 controls by the Perkin-Elmer model 306 atomic absorption spectrophotometer. The main findings were as follows: Cancer of the pancreas was associated with cigarette smoking (relative risk 2.7; P less than 0.05), diabetes mellitus (relative risk 2.1; P less than 0.05), and cholelithiasis (relative risk 3.5; P less than 0.05), but not with alcohol drinking (relative risk 0.7; P less than 0.20) and some other variables. There was a statistically significant increase of serum copper in patients suffering from pancreatic cancer in comparison with noncancer hospital controls. No consistent differences were found with respect to zinc and magnesium.

Psychological stress and fatal heart attack: the Athens (1981) earthquake natural experiment.

The effects of acute and subacute psychological stress caused by a sudden general disaster on mortality from atherosclerotic heart disease (underlying cause) and cardiac events (proximate cause) were investigated by comparing total and cause-specific mortality during the days after a major earthquake in Athens in 1981 with the mortality during the surrounding month and the corresponding periods of 1980 and 1982. There was an excess of deaths from cardiac and external causes on the days after the major earthquake, but no excess of deaths from cancer and little, if any, excess of deaths from other causes. The excess mortality was more evident when atherosclerotic heart disease was considered as the underlying cause (5, 7, and 8 deaths on the first three days, respectively; background mean deaths per day 2.6; upper 95th centile 5) than when cardiac events in general were considered as the proximate cause (9, 11, and 14 deaths on the first three days, respectively; background mean 7.1, upper 95th centile 12).

Epidemiologic assessment of interactions of hepatitis-C virus with seromarkers of hepatitis-B and -D viruses, cirrhosis and tobacco smoking in hepatocellular carcinoma.

A recently introduced enzyme immunoassay procedure for antibodies against the hepatitis-C virus (HCV) was used to test samples from 185 cases with hepatocellular carcinoma (HCC) and 432 hospital controls. The anti-HCV results were examined in conjunction with previously reported data from this study concerning hepatitis-B virus (HBV) serology, hepatitis-D virus (HDV) antibodies, presence of cirrhosis and tobacco smoking. There was evidence for interaction between HBV and HCV in the causation of HCC: as previously reported, the rate ratio (RR) linking the presence of anti-HCV to HCC among subjects positive for hepatitis-B surface antigen (HBsAg) was substantially higher than the corresponding RR among those negative for this marker; furthermore, among HCC patients positive for HBsAg, a high proportion (33/61) of those who were positive for hepatitis-Be antigen (HBeAg) or its antibody were positive for anti-HCV, whereas among HBsAg-positive controls who were also positive for HBeAg or its antibody, none was positive for anti-HCV (0/18; p less than 10(-4)). The anti-HCV-related RR for HCC was also higher among HCC patients with cirrhosis than among those without evidence of co-existing cirrhosis (RR 11.4 vs. 4.4; p = 0.06). In addition, there was some evidence of interaction between tobacco smoking and HCV in the origin of HCC; after controlling for age, sex and HBsAg status, the RR for subjects positive for anti-HCV was 6.8 among smokers but only 3.2 among non-smokers (p = 0.26). By contrast, there was no suggestion of an interaction between anti-HCV and anti-HDV, in agreement with the presumed minimal role, if any, of HDV in HCC etiology. These results support the notion that HCV is involved in the etiology of HCC by advancing, through a chronic liver disease process, carcinogenesis initiated by other factors.

The epidemiology of benign prostatic hyperplasia: a study in Greece.

OBJECTIVE: To assess the epidemiology of benign prostatic hyperplasia (BPH) in a case-control study in greater Athens, Greece. PATIENTS AND METHODS: The study comprised 184 patients surgically treated for BPH within one year of its diagnosis (cases) and 246 patients with no symptoms of BPH who were treated in the same hospitals for minor diseases or conditions (controls). All cases and controls were permanent residents of the greater Athens area, Greece. The data were assessed using unconditional logistic regression. RESULTS: After controlling for age and education, cases and controls had similar distributions for height, body mass index, sibship size and birth order in the parental family, marital status, number of offspring and a series of previous medical diagnoses or surgical operations. The sole exception was surgery for haemorrhoids, that appeared to be related to the incidence of BPH, possibly by chance. There was no evidence that vertex baldness, tobacco smoking, alcohol consumption or coffee drinking increased the risk for BPH. Men who had spent most of their lives in a rural rather than an urban environment appeared to be at reduced risk for BPH. CONCLUSION: The lifestyle factors assessed here have no major effect on the aetiology of BPH.

Determinants of age at menarche as early life predictors of breast cancer risk.

Age at menarche is one of the few established risk factors for breast cancer; identification of its exogenous determinants could throw light on the origins of breast cancer. We have undertaken an epidemiologic study in Greece to ascertain whether: 1) energy intake, an indicator of physical activity, is associated with later age at menarche; 2) energy-adjusted fat intake is related to earlier age at menarche; and 3) other macronutrients and anthropometric variables are predictors of age at menarche. Anthropometric, socio-economic, familiar, nutritional and lifestyle predictors of age at menarche were studied by interviewing in person 345 female students 9 to 16 years old attending 8 schools of Greater Athens. Menarche was the outcome variable in a proportional hazards model assessing the mutually adjusted incidence rate ratio by a series of predictor variables. In a complementary analysis, age at menarche was the dependent variable among menstruating girls. Consistent results were derived from the main and the complementary analysis. Increased height and body mass index accelerate the occurrence of menarche. Maternal and daughter's ages at menarche are correlated, but there is no evidence of an association with paternal education. Various measures of moderate physical activity as well as increased total energy intake were associated with a delay in age at menarche. Energy-adjusted macronutrients were not associated with age at menarche. It appears that an alteration of energy balance in early life through increased physical activity could delay age at menarche and reduce the risk for breast cancer in later life.

Age at first establishment of chronic hepatitis B virus infection and hepatocellular carcinoma risk. A birth order study.

It is frequently assumed that the risk of hepatocellular carcinoma related to hepatitis B virus is higher when chronic hepatitis B virus infection is acquired early in life. This hypothesis has never been directly evaluated. However, firstborn and secondborn children are exposed to common infections after their school enrollment, whereas laterborn children are exposed much earlier, through their older siblings. The authors analyzed sibship size and birth order data from a large case-control study of patients admitted to Athens, Greece, hospitals between April 1976 and October 1984. The analyses included 185 patients with hepatocellular carcinoma, 35 patients with metastatic liver cancer, and 432 other hospital controls. There was a tendency for cases of hepatocellular carcinoma to concentrate at higher birth orders. When the analysis was restricted to cases and controls who were positive for hepatitis B surface antigen, this tendency was even more notable. These results are compatible with the hypothesis that establishment of chronic hepatitis B virus infection at an early age increases the risk of hepatocellular carcinoma substantially more than does chronic infection with this virus established at a later age.

Hepatitis B and C viruses and their interaction in the origin of hepatocellular carcinoma.

Serum taken from patients in a case-control study in Athens, Greece, was used to examine the interactive roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the origin of hepatocellular carcinoma (HCC). An enzyme immunoassay for anti-HCV was used to test serum taken from 185 cases with HCC, 35 cases with metastatic liver cancer (MLC), and 432 hospital controls. Weakly positive anti-HCV results were more strongly related to MLC than to HCC, implying that these anti-HCV results are false positive. By contrast, strongly positive anti-HCV results were significantly related to HCC (relative risk [RR], 6.3), whereas no significant association was evident for MLC (RR, 0.6). The association of anti-HCV with HCC was substantially higher among subjects whose radioimmunoassay was positive for hepatitis B surface antigen (RR, 20.0) than among those whose radioimmunoassay was negative for this marker (RR, 4.8). These findings indicate that HCV infection has an interactive role in the origin of HCC.

Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma.

Tobacco smoking and alcohol drinking histories were obtained from 194 patients with hepatocellular carcinoma (HCC) and 456 hospital controls, and the results were analysed in conjunction with the results of serological determinations of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) in all subjects, as well as the presence or absence of cirrhosis in HCC patients. The relative risk (RR) of HCC (and 95% confidence interval) among HBsAg-positive subjects was 13.7 (8.0-23.5), whereas the excess risk among antibody-positive subjects was small and statistically non-significant. In the presence of cirrhosis the RR for HBsAg-positive subjects was considerably higher (30.7 vs. 7.1 among HBsAg-positive subjects without cirrhosis) indicating that HBV may affect the development of HCC through at least two different and potentially multiplicative mechanisms (DNA integration and liver regeneration). Moderate ethanol consumption does not affect the risk of HCC, but there is a statistically significant and dose-dependent association between tobacco smoking and HBsAg-negative HCC. In most of the developed countries of Europe and North America, where the prevalence of HBsAg carrier state is very low and tobacco smoking very common, more cases of HCC may be due to tobacco smoking than to HBV, even though the RR for HCC is much higher among HBsAg carriers than among tobacco smokers.