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PubMed1991

Possible role of diet as a host factor in the aetiology of tobacco-induced lung cancer: an ecological study in southern and northern Italy.

Statistical data on smoking and dietary habits in northern and southern Italy were compared and related to mortality rates for lung cancer. Age-adjusted mortality rates for lung cancer in the years 1980 and 1982 were lower in southern than in northern Italy. The proportion of smokers, as surveyed in 1977, was similar in the two geographical areas. Dietary habits in southern Italy, however, were characterized during the years 1960 through 1965, by a low consumption of saturated and polyunsaturated lipids, and a high consumption of foods of vegetable origin. Our data suggest that diet may modify the carcinogenic effect of tobacco in lung cancer.

Adolescent↗
PubMed2003

Cigarette consumption and socio-economic circumstances in adolescence as predictors of adult smoking.

AIM: To investigate effects of cigarette consumption level and socio-economic circumstances during adolescence on adult smoking. METHODS: 1958 British birth cohort (all births 3-9 March 1958). Logistic regression used to predict (i) smoking at 41 years and (ii) persistent smoking (at 23, 33 and 41 years) from cigarette consumption and socio-economic circumstances at 16 years, indicated by social class and educational qualifications. RESULTS: Of 6537 subjects with full smoking history, 30% smoked at 16 years, 23% smoked at 41 years and 19% smoked at 23, 33 and 41 years (persistent smokers). Heavier smokers at 16, 23 and 33 years were more likely to smoke at 41 years than lighter smokers. The odds ratio (OR) of smoking at 41 years was 2.5 for men and 3.0 for women who smoked >/=60 cigarettes/week at age 16, relative to <20 cigarettes/week. Subjects from manual social backgrounds and those with no qualifications had elevated risks of being a smoker at 41 years or a persistent smoker. These effects were robust to adjustment for adolescent consumption level (e.g. adjusted OR for no qualifications was 3.8). However, adolescent consumption level modified the effect of educational achievements. Among lighter adolescent smokers, those gaining higher qualifications had lower prevalence of smoking at 41 years (16%) than men with no qualifications (83%); among heavier adolescent smokers, prevalence was more similar for subjects with higher (56%) and no qualifications (69%). CONCLUSIONS: Socio-economic background appears to influence adult smoking behaviour separately from adolescent cigarette consumption which is a recognized measure of nicotine dependence. There was some evidence that effects of early nicotine dependence are modified by educational achievements.

Adolescent↗
PubMed1991

Radiobiological fundamentals in radioepidemiology and radiation protection.

Radiation is a convenient tool to study fundamental processes of life. Biological effects of irradiation may result from indirect actions which are mediated by free radicals (e.g. OH-radicals) or from direct actions which involve ionizations in the DNA and other biomolecules. Damage to the DNA is the principal, but not exclusive target for cell death, loss of reproductive integrity, mutation, cancer, developmental anomalies and other radiobiological effects. Repair of damaged DNA and cellular recovery processes play an essential role in affecting the survival of cells. Dose, dose rate, radiation quality, biological and chemical modifiers also have a pronounced effect upon the extent of radiation responses. The biological effects of ionizing radiation are somatic or hereditary and can further be classified into stochastic and deterministic effects. For radiation epidemiology and protection the stochastic action is more relevant because the probability of an effect is a function of dose, without a threshold. Induction of cancer, hereditary diseases and probably also mental retardation are regarded as stochastic effects.

Cell Survival↗
PubMed2005

Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma: a case-control study in a Chinese population.

The incidence of lung adenocarcinoma (AC) has been increasing over recent decades. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent carcinogens and reproducibly induces a high incidence of lung AC in laboratory animals. In addition to its genotoxic effects, NNK has also epigenetic effects on lung cells by functioning as an agonist for beta adrenergic receptors and stimulating the signal pathways that lead to lung AC. Beta-2 adrenergic receptor (ADRB2) expressed on bronchial smooth muscle is a well-defined target for asthma treatment that has epidemiological implications in lung cancer development. And biochemical effect and pharmacogenetic relevance of regulatory and coding variants of ADRB2 have been well documented. Aiming to test whether the genetic variants of ADRB2 modify risk of lung AC, we compared the manifestation of three common single nucleotide polymorphisms (SNPs) of ADRB2 (G-1023A, G-654A, and A46G (Gly16Arg)) between 313 patients with lung AC and 321 controls. Overall association was not observed between risk and either individual of the three SNPs or their combined haplotypes. However, in the subgroup of young subjects < or =50 years old, significant association was observed for G-1023A (allele based OR, 1.82; 95% CI, 1.12-2.95), A46G (Gly16Arg) (allele based OR, 0.64; 95% CI, 0.40-1.03), and the haplotype A(-1023)A(46) (OR 2.62; 95% CI 1.30-5.27). Our results do not support a major independent role of ADRB2 polymorphisms in lung AC risk, suggesting that functional variants of other genes involved in the NNK epigenetic pathway of carcinogenesis should be investigated.

Asian People↗
PubMed1997

Epidemiology of non-insulin-dependent diabetes mellitus and its macrovascular complications. A basis for the development of cost-effective programs.

Non-insulin-dependent diabetes mellitus is a major health problem in developed countries. The descriptive epidemiology of this disease and its cardiovascular complications are reviewed, and insulin resistance is identified as a common risk factor for both of them. The requirements for cost-effective programs to modify insulin resistance to prevent this disorder and its cardiovascular complications are discussed.

Adult↗
PubMed1991

Lipid intake and atherosclerosis.

The importance of diet in the prevention and treatment of atherosclerosis is well known. Among the different nutrients, lipids certainly have a primary role. Dietary cholesterol can influence the progression of atherosclerosis by increasing cholesterol levels or by modifying the composition of lipoproteins. Epidemiological and clinical studies have clearly demonstrated a relationship between the intake of saturated fatty acids and atherosclerosis. Among these fatty acids, stearic acid has the smallest effect on cholesterol levels. Until a few years ago it was though that monounsaturated fatty acids (MUFA) did not affect lipoprotein metabolism. However, very recently it has been shown that MUFA have the same hypocholesterolemic effect as polyunsaturated fatty acids; moreover they do not induce a decrease in high-density lipoprotein cholesterol. Therefore the overall metabolic effect of MUFA seems to be beneficial.

Arteriosclerosis↗
PubMed2003

The decline of hepatitis B viral infection in South-Western Saudi Arabia.

OBJECTIVE: Hepatitis B virus (HBV) infection is endemic in the Kingdom of Saudi Arabia (KSA). The Jizan region in the South-Western area of the country was noted for a high prevalence of hepatitis B surface antigen (HbsAg) carrier rate. The study was carried out to determine the prevalence of HBsAg and other markers of HBV among residents of Jizan and evaluate the impact of the measures adopted in the last decade, to control HBV. METHODS: The study was carried out between 1995 and 1998. The subject were studied in 4 groups: Group A consisted of voluntary blood donors (n=14883) tested within the blood banking system during the time period June 1995 to June 1997, Group B were patients treated in the hospitals (n=4692) during the period June 1995 to June 1996, Group C consisted of volunteers recruited from the community (n=1172) and Group D children aged <10 years (n=229). Serum samples were obtained from the subjects tested for HBsAg, total antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus. RESULTS: Hepatitis B surface antigen was positive in 5.4% of 14883 voluntary blood donors (Group A) and in 5.1% of 1172 persons recruited from the community (Group C) 40.2% were positive for at least one marker of HBV. The prevalence of HBsAg in-patients in Group B was 9.7% (456 of 4692). These prevalence rates are significantly lower than the prevalence of 12% and 32% reported in 1985 and 1986. Only 2 (0.9% of 229) children in Group D were positive for HBsAg, indicating a major decline from the rate of 8.8% observed in an earlier survey. CONCLUSION: The low prevalence of HBsAg in children, provides evidence for the effectiveness and efficacy of the integration of hepatitis B vaccination into the extended program of immunization in KSA. The significant decline of HBV markers among unvaccinated Saudi adults indicated an indirect effect of other factors (for example health education and socio-economic progress) on the prevalence and transmission of HBV in Jizan. In areas of high endemicity, the epidemiological characteristics HBV are modified significantly by the combination of HBV vaccination and other complimentary control strategies.

Adolescent↗
PubMed1995

Interaction between dietary pattern and alcohol intake on the risk of liver cirrhosis. The Provincial Group for the Study of Chronic Liver Disease.

In order to assess the inter-relationship between nutritional intake and alcohol consumption on the risk of liver cirrhosis we performed a hospital-based retrospective case-control study. We enrolled 115 cases admitted to hospital for liver decompensation at their first diagnosis of liver cirrhosis and 167 hospital controls without evidence of liver disease admitted for acute diseases unrelated to alcohol intake. Daily alcohol intake and average nutrient intake were measured throughout the patient's life, using a reproducible questionnaire. No dose-effect relationship was found between nutrient intake and risk of cirrhosis using classical association statistical methods. We then corrected the intake of each nutrient for the total caloric intake and this energy-adjusted nutrient intake was used in a logistic regression model together with alcohol intake, viral B and C hepatitis markers, age and gender. Using this approach, carbohydrates intake were shown to have a protective effect on the risk of cirrhosis, whereas saturated lipid intake had a significant multiplicative effect on the risk associated with alcohol consumption. By comparison with the teetotalers category who had an average daily intake of saturated fatty acids lower than 40.3 g (reference category; OR = 1), drinkers of more than 100 g ethanol per day showed ORs ranging from 14.2 (95% confidence interval 2.0-101.0) for consumers of less than 40.3 g fatty acid per day, to 39.0 (95% confidence interval 5.0-305.1) for consumers of more than 40.4 g fatty acid per day. In conclusion we give additional evidence on the relationship between diet and risk of cirrhosis, whereby saturated lipid intake multiplies the risk associated with alcohol intake. However, caution should be used to interpret such results, since they seem to suggest that diet but not a particular nutrient can modify the effect of alcohol on the risk of cirrhosis. The present lack of agreement on the mechanisms and the nutrients involved in the pathogenesis of alcoholic liver injury should stimulate wider epidemiological studies using modern nutritional techniques.

Alcohol Drinking↗
PubMed2006

Confounder selection in environmental epidemiology: assessment of health effects of prenatal mercury exposure.

PURPOSE: The purpose of the study is to compare different approaches to the identification of confounders needed for analyzing observational data. Whereas standard analysis usually is conducted as if the confounders were known a priori, selection uncertainty also must be taken into account. METHODS: Confounders were selected by using backward elimination (BE), change in estimate (CIE) method, Akaike information criterion, Bayesian information criterion (BIC), and an empirical approach using a priori information. A modified ridge regression estimator, which shrinks effects of confounders toward zero, also was considered. For each criterion, uncertainty in the estimated exposure effect was assessed by using bootstrap simulations for which confounders were selected in each sample. These methods were illustrated by using data for mercury neurotoxicity in Faroe Islands children. Point estimates and standard errors of mercury effects on confounder-sensitive neurobehavioral outcomes were calculated for each selection procedure. RESULTS: The full model and the empirical a priori model showed approximately the same precision, and these methods were (slightly) inferior to only modified ridge regression. Lower precisions were obtained by using BE with a low cutoff level, BIC, and CIE. CONCLUSIONS: Standard analysis ignores model selection uncertainty and is likely to yield overoptimistic inferences. Thus, the traditional BE procedure with p = 5% should be avoided. If data-dependent procedures are required for confounder identification, we recommend that inferences be based on bootstrap statistics to describe the selection process.

Animals↗
PubMed2003

Health, wealth, and air pollution: advancing theory and methods.

The effects of both ambient air pollution and socioeconomic position (SEP) on health are well documented. A limited number of recent studies suggest that SEP may itself play a role in the epidemiology of disease and death associated with exposure to air pollution. Together with evidence that poor and working-class communities are often more exposed to air pollution, these studies have stimulated discussion among scientists, policy makers, and the public about the differential distribution of the health impacts from air pollution. Science and public policy would benefit from additional research that integrates the theory and practice from both air pollution and social epidemiologies to gain a better understanding of this issue. In this article we aim to promote such research by introducing readers to methodologic and conceptual approaches in the fields of air pollution and social epidemiology; by proposing theories and hypotheses about how air pollution and socioeconomic factors may interact to influence health, drawing on studies conducted worldwide; by discussing methodologic issues in the design and analysis of studies to determine whether health effects of exposure to ambient air pollution are modified by SEP; and by proposing specific steps that will advance knowledge in this field, fill information gaps, and apply research results to improve public health in collaboration with affected communities.

Air Pollution↗
PubMed1991

Left ventricular size, mass and function in relation to the duration and quantity of heavy drinking in alcoholics.

Left ventricular (LV) hypertrophy and mild dysfunction are frequently observed in alcoholics but little is known about how they relate to the duration and severity of alcohol abuse. LV size, mass and function were studied using echocardiography and systolic time intervals in 78 middle-aged male alcoholics who also gave detailed accounts of the duration of heavy drinking, the quantity of recent ethanol consumption and the duration of abstinence. Compared with 34 healthy nonalcoholics, alcoholics had a higher LV mass index (85 +/- 2 [mean +/- standard error] vs 77 +/- 2 g/m2, p = 0.001), a thicker posterior wall (11 +/- 0.2 vs 10 +/- 0.2 mm, p = 0.02), a longer end-systolic diameter index (18 +/- 0.3 vs 17 +/- 0.3 mm/m2, p = 0.02), and a higher preejection period/ejection time ratio (0.36 +/- 0.01 vs 0.33 +/- 0.01, p = 0.002). In multivariate linear regression models, these abnormalities proved independent of the drinking history, except that posterior wall thickness was weakly related to the duration of heavy drinking (standardized correlation coefficient 0.36, p = 0.01). Univariate analyses suggested that the LV mass index and systolic time interval ratio had, if anything, a curvilinear relation to the total duration of heavy alcohol consumption. It is concluded that the LV hypertrophy and dysfunction found in alcoholics are poorly related to the duration and severity of self-reported alcohol abuse. Together with other data, this suggests that there is no simple linear dose-injury relation in the long-term cardiotoxicity of ethanol. Factors modifying the myocardial effects of ethanol need to be studies more in the future.

Adult↗
PubMed2006

Early renal structure alteration in rat offspring from dams fed low protein diet.

To investigate the early renal alterations due to severe maternal protein restriction (MPR) Wistar dams received 23% (normal protein, NP) or 5% (low protein, LP) chow during gestation and lactation periods. In NP offspring at birth, the cortex-to-medulla (C/M) ratio was 35% greater in female than in male offspring and the mature/immature glomeruli ratio was lower in both sexes of LP offspring than in the matched NP ones (by 20%). At birth and at weaning the kidney of the LP offspring showed fewer glomeruli (40% less) than the age-matched NP offspring. The NP female offspring had almost 20% fewer glomeruli than the matched male offspring. At weaning, the number of glomeruli was positively correlated with BM at birth (R=0.86; P<0.001). The effects of gender and maternal protein restriction, both individually and overall, based on biometrical and stereological parameters were: day 1, MPR largely responsible for the majority of alterations observed in LP groups, however gender influenced C/M ratio; day 21, MPR and gender interacted and modified the number of glomeruli per kidney. The early adverse of MPR effect on renal development is disproportionate between mature and immature glomeruli at birth leading to fewer glomeruli at weaning. This supports epidemiological data in humans underlying why fetuses with low birth weight carry an increased risk of mortality from chronic diseases in adulthood, including hypertension.

Animals↗
PubMed2003

Health effects from stratospheric ozone depletion and interactions with climate change.

The potential health effects of elevated levels of ambient UV-B radiation are diverse, and it is difficult to quantify the risks, especially as they are likely to be considerably modified by human behaviour. Nevertheless epidemiological and experimental studies have confirmed that UV radiation is a definite risk factor for certain types of cataract, with peak efficacy in the UV-B waveband. The causal link between squamous cell carcinoma and cumulative solar UV exposure has been well established. New findings regarding the genetic basis of skin cancer, including studies on genetically modified mice, have confirmed the epidemiological evidence that UV radiation contributes to the formation of basal cell carcinomas and cutaneous melanomas, For the latter, animal models have demonstrated that UV exposure at a very young age is more detrimental than exposure in adulthood. Although suppression of certain immune responses has been recognised following UV exposure, the impact of this suppression on the control of infectious and autoimmune diseases is largely unknown. However, studies on several microbial infections have indicated significant consequences in terms of symptoms or reactivation of disease. The possibility that the immune response to vaccination could be depressed by UV-B exposure is of considerable concern. Newly emerging possibilities regarding interactions between ozone depletion and global climate change further complicate the risk assessments for human health but might result in an increased incidence of cataracts and skin cancer, plus alterations in the patterns of certain categories of infectious and other diseases.

Cataract↗
PubMed2006

Use of genetically modified viruses and genetically engineered virus-vector vaccines: environmental effects.

Despite major therapeutic advances, infectious diseases remain highly problematic. Recent advancements in technology in producing DNA-based vaccines, together with the growing knowledge of the immune system, have provided new insights into the identification of the epitopes needed to target the development of highly targeted vaccines. Genetically modified (GM) viruses and genetically engineered virus-vector vaccines possess significant unpredictability and a number of inherent harmful potential hazards. For all these vaccines, safety assessment concerning unintended and unwanted side effects with regard to targeted vaccinees has always been the main focus. Important questions concerning effects on nontargeted individuals within the same species or other species remain unknown. Horizontal transfer of genes, though lacking supportive experimental or epidemiological investigations, is well established. New hybrid virus progenies resulting from genetic recombination between genetically engineered vaccine viruses and their naturally occurring relatives may possess totally unpredictable characteristics with regard to host preferences and disease-causing potentials. Furthermore, when genetically modified or engineered virus particles break down in the environment, their nuclei acids are released. Appropriate risk management is the key to minimizing any potential risks to humans and environment resulting from the use of these GM vaccines. There is inadequate knowledge to define either the probability of unintended events or the consequences of genetic modifications. The objective of this article is to highlight the limitations in environmental risk assessment and raise awareness of the potential risks involving the use of genetically modified viruses and genetically engineered virus-vector vaccines.

Environmental Pollution↗
PubMed2000

Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s.

BACKGROUND: In the last decades, studies have estimated the upper gastrointestinal tract bleeding/perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also included the effect of patterns of NSAID use, risk factors for UGIB, and modifiers of NSAID effect. METHODS: Systematic review of case-control and cohort studies on serious gastrointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected according to predefined criteria. Two researchers extracted the data independently. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons for heterogeneity were considered. RESULTS: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with advanced age or a history of peptic ulcer had the highest absolute risks. The pooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was maintained during treatment and returned to baseline once treatment was stopped. A clear dose response was observed. There was some variation in risk between individual NSAIDs, though these differences were markedly attenuated when comparable daily doses were considered. CONCLUSIONS: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses to reduce the UGIB risk associated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.

Age Factors↗
PubMed1997

Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data.

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+ years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR = 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process.

Adolescent↗
PubMed1991

Cardiovascular risk factors and the effects of intervention.

Cardiovascular risk factors can be substantially modified by changes in life-style such as diet, exercise, smoking cessation, and moderation of alcohol consumption. In turn, these can reduce blood pressure, heart rate at rest, and blood lipid concentrations. Epidemiologic evidence shows that for every 1% change in serum cholesterol levels, there is a 3% change in the likelihood of developing coronary heart disease. In addition, a long-term (5-year) change of 5 to 6 mm Hg in diastolic blood pressure can reduce the chances of stroke by 35 to 40% and of coronary heart disease by 20 to 25%. The full impact of this broad range of interventions on population health has still to be fully realized in many countries, including the United Kingdom, however it is likely to be considerable. Some of the recent evidence in support of such cardiovascular risk factor modification is selectively reviewed.

Alcohol Drinking↗
PubMed1995

Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?

Are there empirical examples of strong confounding effects? Textbooks usually show examples of weak confounding or use hypothetical examples of strong confounding to illustrate the paradoxical consequences of not separating out the effect of the studied exposure from that of second factor acting as a confounder. HIV infection is a candidate strong confounder of the spuriously high association reported between consumption of poppers, a sexual stimulant, and risk of Kaposi's sarcoma in the early phase of the AIDS epidemic. To examine this hypothesis, assumptions must be made on the prevalence of HIV infection among cases of Kaposi's sarcoma and on the prevalence of heavy popper consumption according to HIV infection in cases and controls. Results show that HIV infection may have confounded the poppers-Kaposi's sarcoma association. However, it cannot be ruled out that HIV did not qualify as a confounder because it was either an intermediate variable or an effect modifier of the association between popper inhalation and Kaposi's sarcoma. This example provides a basis to discuss the mechanism by which confounding occurs as well as the practical importance of confounding in epidemiologic research.

Confounding Factors, Epidemiologic↗