Data sources and validity of epidemiological studies on diabetes.
Explore the source record for details and available documents.
Blindness↗
Biomedical subjects
F Merletti
Publications and source records attributed to F Merletti.
Lung cancer and cigarette smoking in Europe: an update of risk estimates and an assessment of inter-country heterogeneity.
Ten case-control studies have been carried out in 6 European countries to investigate the major risk factors for lung cancer. Carcinogenic effect from cigarette smoke was the most relevant interest in our study, which has included 7,609 cases of lung cancer and 10,431 controls, mainly population based. The results indicate elevated odds ratios (ORs; 23.9 among men and 8.7 among women) with attributable risks exceeding 90% for men and close to 60% for women. A large, and statistically significant, variability of the results across countries was detected after adjusting for the most common confounding variables, and after controlling, at least in part, for the instability of the ORs due to the small number of non-smokers in some of the study subsets. This pattern of lung cancer risk associated with cigarettes smoke, across different European regions, reflects inherent characteristics of the studies as well as differences in smoking habits, particularly calendar periods of starting, and it is likely to have been influenced by effect modifiers like indoor radon exposure, occupation, air pollution and dietary habits.
Aged↗
Increasing trend of type I diabetes in children and young adults in the province of Turin (Italy). Analysis of age, period and birth cohort effects from 1984 to 1996.
AIMS/HYPOTHESIS: This study aimed to determine if the incidence of Type I (insulin-dependent) diabetes mellitus increased over time and if the time trend is attributable to linear trend, calendar period or birth cohort effects. METHODS: This study was based on a cohort of subjects aged 0-29 years from 1984 to 1996, who resided in the province of Turin, Italy. Poisson regression models were used to estimate the effect of sex, age, calendar time and cohorts on incidence rates. RESULTS: The mean incidence rate in the age group of 0 to 29 years was 7.78 of 100,000 person-years (95% confidence interval: 7.26-8.32), with a lower risk in women than in men [rate ratio (RR): 0.76 (0.67-0.88)]. We found a trend of incidence increasing over time (annual increase of risk 2.25 % a year, 95 % CI 0.44-4.10). In Poisson regression analysis we found that the best model was the one with sex, age and a linear term attributable to either calendar period or cohort effects. The linear term corresponds to a RR of 1.12 (1.02-1.22,p = 0.015) for each 5-year age span. CONCLUSION/INTERPRETATION: We found that the time trend in this Mediterranean area was similar in magnitude to that reported in northern European countries. The increase was linear in pattern, each birth cohort and each calendar period showing a higher risk than the preceeding one with some evidence of two steep increases in the incidence of Type I diabetes centered on the years 1964 and 1984. We found that the incidence of diabetes increased in the 0 to 14 age group and also in the older age group of 15 to 29 years and that the age-period models were not statistically significantly better than the age-cohort models.
Adolescent↗
Are alcohol intake and smoking associated with mycosis fungoides? A European multicentre case-control study.
The incidence of mycosis fungoides (MF) is low, and the aetiology of the disease is unknown. The aim of this study was to investigate whether wine consumption protects against the disease and whether smoking constitutes a risk factor. This paper is part of the European Rare Cancers Study that tries to determine the risk factors for seven selective rare cancers, including mycosis fungoides, involved in the development of cancer. A multicentre case-control study was conducted in six European countries. Only incident cases with confirmed histology were included in the analysis which include a total of 76 cases of MF and 2899 controls. Wine intake had no protective effect; on the contrary the consumption of more than 24 g of alcohol per day was associated with a high risk of MF (odds ratio (OR)=3.02, 95% confidence interval (CI), 1.34-6.79), after adjusting for centre, country, age, sex and education. There was a dose-dependent increase in the risk of MF with increased smoking habits, albeit the observed trend was not statistically significant. A combined exposure to high tobacco and alcohol use yielded a significantly increased risk factor for MF (P=0.0073). Alcohol intake was associated with MF.
Adult↗
Medical risk factors for small-bowel adenocarcinoma with focus on Crohn disease: a European population-based case-control study.
BACKGROUND: Crohn disease and biliary diseases have been associated with small-bowel adenocarcinoma (SBA). We examined how medical conditions affect the risk of SBA. METHODS: A population-based European multicentre case-control study during the period 1995-97 including 95 histologically verified cases of SBA along with 3335 population controls; 70 cases (74%) and 2070 (62%) controls were interviewed about previous medical conditions. RESULTS: Crohn disease was identified in two SBA cases (both located in ileum) and two controls; odds ratio (OR) 53.6 (6.0-477) (95% CI in parentheses). Only one case and no controls had had long-standing Crohn disease. Coeliac disease was associated with SBA (2 cases, 0 controls), but one of the cases was diagnosed at the same time as the SBA. Overall, people with a history of gallstones had no increased risk of SBA. The OR was exclusively increased during the 3-year period preceding the SBA diagnosis. Previous gallstone surgery, which may be a sign of severe gallstone disease, was not associated with SBA. Liver cirrhosis, hepatitis or medical treatments with radioactive substances or corticosteroid tablets were not associated with this disease. Cases with SBA had an increased prevalence of anaemia; OR 15.3 (2.5-92.1). An association between low educational level and SBA was found; OR 1.75 (1.0-3.0). CONCLUSION: This study supports Crohn disease and coeliac disease being strong but rare risk factors for SBA. Previous gallstones were unrelated to SBA, and detection bias may account for the findings in earlier studies.
Adenocarcinoma↗
Lung cancer and cigarette smoking in women: a multicenter case-control study in Europe.
The association between cigarette smoking and lung cancer risk in women was investigated within the framework of a case-control study in 9 centres from 6 European countries. Cases were 1,556 women up to 75 years of age with histologically confirmed primary lung cancer; 2, 450 controls with age distribution similar to cases were selected. The predominant cell type was adenocarcinoma (33.5%), with similar proportions for squamous-cell type (26.4%) and small-cell carcinoma (22.3%). Overall, smoking cigarettes at any time was associated with a 5-fold increase in lung cancer risk (odds ratio 5.21, 95% confidence interval 4.49-6.04); corresponding figures for current smoking habits were 8.94, 7.54-10.6. The association showed a dose-response relationship with duration of the habit and daily and cumulative lifetime smoking. A significant excess risk of 70% was associated with every 10 pack-years smoked. After 10 years of smoking cessation, the relative risk decreased to 20% compared to current smokers. The following characteristics were associated with a higher relative risk: inhalation of smoke, smoking non-filter cigarettes, smoking dark-type cigarettes and starting at young age. The association was observed for all major histological types, being the strongest for small-cell type carcinoma, followed by squamous-cell type and the lowest for adenocarcinoma. The proportion of lung-cancer cases in the population attributable to cigarette smoking ranged from 14% to 85%. We concluded that women share most features of the association between cigarette smoking and lung cancer observed in men.
Adult↗
Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer.
Fas/Apo-1 (CD95) triggers programmed cell death (PCD) and is involved in immune response control and cell-mediated cytotoxicity. In the autoimmune/lymphoproliferative syndrome (ALPS), inherited loss-of-function mutations of the Fas gene cause nonmalignant lymphoproliferation and autoimmunity. We have recently identified an ALPS-like clinical pattern (named autoimmune lymphoproliferative disease [ALD]) in patients with decreased Fas function, but no Fas gene mutation. They also displayed decreased PCD response to ceramide, triggering a death pathway partially overlapping that used by Fas, which suggests that ALD is caused by downstream alterations of the Fas signaling pathway. Decreased Fas function is also involved in tumor development, because somatic mutations hitting the Fas system may protect neoplastic cells from immune surveillance. This work assessed the inherited component of the ALD defect by evaluating Fas- and ceramide-induced T-cell death in both parents and 4 close relatives of 10 unrelated patients with ALD. Most of them (22 of 24) displayed defective Fas- or ceramide-induced (or both) cell death. Moreover, analysis of the family histories showed that frequencies of autoimmunity and cancer were significantly increased in the paternal and maternal line, respectively. Defective Fas- or ceramide-induced T-cell death was also detected in 9 of 17 autoimmune patients from 7 families displaying more than a single case of autoimmunity within first- or second-degree relatives (multiple autoimmune syndrome [MAS] patients). Autoimmune diseases displayed by ALD and MAS families included several organ-specific and systemic forms. These data suggest that ALD is due to accumulation of several defects in the same subject and that these defects predispose to development of cancer or autoimmune diseases other than ALPS/ALD.
Adolescent↗
Temporal trends in incidence rates of Type I diabetes in Germany: birth cohort and calendar period effects.
Explore the source record for details and available documents.
Age Factors↗
Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case-control study.
OBJECTIVE: To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). METHODS: A population-based European multi-center case-control study was conducted from 1995 to 1997. RESULTS: After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5-8.0 and 3.4 (95% CI 1.3-9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. CONCLUSIONS: A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.
Adenocarcinoma↗
Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy.
Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.
Adenocarcinoma↗
Occupational risks for lung cancer among nonsmokers.
We conducted a case-control study in 12 European study centers to evaluate the role of occupational risk factors among nonsmokers. We obtained detailed occupational histories from 650 nonsmoking cases (509 females/141 males) and 1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori definition of occupations and industries that are known (list A) or suspected (list B) to be associated with lung carcinogenesis, we calculated odds ratios (ORs) for these occupations, using unconditional logistic regression models and adjusting for sex, age, and center effects. Among nonsmoking men, an excess relative risk was observed among those who had worked in list-A occupations [OR = 1.52; 95% confidence interval (C) = 0.78-2.97] but not in list-B occupations (OR = 1.05; 95%), CI = 0.60-1.83). Among nonsmoking women, there was an elevation of risk for list-A occupations (OR = 1.50; 95% CI = 0.49-4.53), although this estimate was imprecise, given that less than 1% of cases and controls were exposed. Exposure to list-B occupations was associated with an increase in relative risk (OR = 1.69; 95% CI = 1.09-2.63) in females, but not in males. Women who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98-3.40). Our findings confirm that certain occupational exposures are associated with an increased risk for lung cancer among both female and male nonsmokers; however, knowledge on occupational lung carcinogens is biased toward agents to which mainly men are exposed.
Adult↗
Occupation and small bowel adenocarcinoma: a European case-control study.
OBJECTIVES: Because of the rarity of small bowel adenocarcinoma (SBA), little is known about the aetiology of this disease. This study aimed to identify occupational clustering of cases SBA as a systematic approach to new hypotheses on the aetiology of this disease. METHODS: A European multicentre case-control study was conducted in 1995-7, inclusive. Incident cases aged 35-69 years with SBA (n=168) were recruited before acceptance by a pathologist. Altogether 107 cases and 3915 controls were accepted, of which 79 cases, 579 colon cancer controls, and 2070 population controls were interviewed. RESULTS: The strongest industrial risk factors for SBA taking account of 10 years' exposure lag were dry cleaning, manufacture of workwear, mixed farming (women), and manufacture of motor vehicles (men). A significantly increased risk of SBA (odds ratio (OR) and 95% confidence interval (95% CI)) was found among men employed as building caretakers, OR 6.7 (1.7 to 26.0) and women employed as housekeepers, OR 2.2 (1.1 to 4.9); general farm labourers, OR 4.7 (1.8 to 12.2); dockers, OR 2.9 (1.0 to 8.2); dry cleaners or launderers, OR 4.1 (1.2 to 13.6); and textile workers (sewers or embroiderers), OR 2.6 (1.0 to 6.8). For the last four groups, together with welders OR 2.7 (1.1 to 6.6) (men) an exposure-response pattern was found when calculating the ORs for jobs held 1-5 years and >5 years, with never having held the job as reference. The ORs (95% CIs) for 1-5 years and >5 years were 4.3 (0.4 to 44.0) and 3.5 (0.9 to 13.7), 3.0 (0.3 to 26.2) and 4.3 (0.9 to 21.2), 4.6 (0.4 to 48.1) and 11.0 (2.0 to 60.4), 1.3 (0.2 to 11.0) and 5.8 (2.0 to 17.2), and 2.8 (0.3 to 23.8) and 4.6 (1.3 to 16.6), respectively, for each of these occupations. Among welders, people performing semiautomatic arc welding (MIG/MAG) were identified as a high risk group (OR 5.0 (1.3 to 19.6)). CONCLUSIONS: This explorative study suggests an increased occurrence of SBA in certain occupations, which needs further evaluation.
Adenocarcinoma↗
Effect of Sardinian heritage on risk and age at onset of type 1 diabetes: a demographic case-control study of Sardinian migrants.
BACKGROUND: Children of Sardinian heritage are at high risk of type 1 diabetes, whereas no data are available in young adults. Age at onset of type 1 diabetes could be associated with different relative weight of genetic susceptibility and environmental determinants in the pathogenesis of the disease. We test this hypothesis in subjects with Sardinian heritage 0-29 years of age living in the city of Turin, a highly industrialized area in Northern Italy. METHODS: In all, 202 cases with onset of type 1 diabetes aged 0-29 years during 1984-1991 and 1010 controls randomly selected from residents of the city of Turin, frequency-matched by sex and year of birth to cases, were included in this study. Name and place of birth of parents were ascertained by postal inquiry and linkage with city population and census files. Social class was based on the highest educational level of parents abstracted from 1991 and 1981 census files. RESULTS: Differential effects on risk of type 1 diabetes of Sardinian heritage and social class in the age groups 0-14 and 15-29 years were found. In children with one and both Sardinian parents the odds ratios (OR) were 2.09 (95% CI : 0.85-5.15) and 3.20 (95% CI : 0.75-13.64); in young adults 0.81 (95% CI : 0.18-3.64) and 1.95 (95% CI : 0.51-7.40), respectively. In subjects with low social class the OR were 1.16 (95% CI : 0.68-1.97) in children and 0.66 (95% CI : 0.41-1.05) in young adults. CONCLUSIONS: This study shows higher risk of type 1 diabetes in subjects of Sardinian heritage; higher risk in children than in young adults and a protective effect of low social class in young adults. These findings are consistent with the hypothesis of heterogeneity of type 1 diabetes by age at onset, with prevailing genetic effect in childhood and environmental determinants in adulthood.
Adolescent↗
Risk of lung cancer from exposure to environmental tobacco smoke from cigars, cigarillos and pipes.
Explore the source record for details and available documents.
Case-Control Studies↗
Cigar and pipe smoking and lung cancer risk: a multicenter study from Europe.
BACKGROUND: Because limited information is available on the quantitative association between consumption of tobacco products other than cigarettes and lung cancer risk, we undertook a case-control study of this relationship. METHODS: We investigated lung cancer risk among smokers of cigars and/or cigarillos only and of pipes only and compared these risks with the risk of smokers of cigarettes only in a case-control study conducted in seven European areas. Our study population consisted of 5621 male case patients with lung cancer and 7255 male control subjects. Each subject or his proxy was interviewed with respect to the subject's smoking history and other risk factors for lung cancer. RESULTS: The odds ratio (OR) for smoking cigars and cigarillos only was 9.0 (95% confidence interval [CI] = 5.8-14.1), based on 43 exposed case patients and 77 exposed control subjects, and the OR for smoking a pipe only was 7.9 (95% CI = 5.3-11.8), representing 61 case patients and 129 control subjects. The OR for smoking cigarettes only was 14.9 (95% CI = 12.3-18.1), based on 4204 case patients and 3930 control subjects. A dose-response relationship was present for duration of use and cumulative consumption both for cigars and cigarillos and for pipe tobacco. An effect was also suggested for inhalation of cigar and cigarillo smoke. The dose-response relationships between lung cancer risk and either duration of smoking or average and cumulative consumption were similar for cigar and cigarillo smoking, pipe smoking, and cigarette smoking. CONCLUSION: Our results suggest that smoking of European cigars, cigarillos, and pipe tobacco might exert a carcinogenic effect on the lung comparable to that of cigarettes.
Age Factors↗
Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of type II (non-insulin-dependent) diabetes mellitus.
The aims of this study were to assess the impact of diabetes and associated variables (fasting plasma glucose, blood pressure, antidiabetic treatment, body mass index) on general and cause-specific mortality in an Italian population-based cohort with Type II (non-insulin-dependent) diabetes mellitus, comprising mainly elderly patients. The patients (n = 1967) who had Type II diabetes were identified in 1988 with an 80% estimated completeness of ascertainment. In 1995, a mortality follow-up (98% completeness) of the cohort was done amounting to a total of 11153 person-years. Observed and expected number of deaths were 577 and 428.7, respectively, giving a standardized mortality ratio (SMR) of 1.35 (95% CI 1.24-1.46). The most common underlying causes of death were malignant neoplasm, ischaemic heart disease and cerebrovascular diseases, which accounted for 18%, 17.8% and 17.5% of deaths, respectively. Cardiovascular disease as a whole (international classification of disease ICD-9 390-459) accounted for 260 of 577 deaths (SMR 1.21, 95% CI 1.07-1.36). In internal analysis, the most important predictors of general mortality were insulin-treatment (relative risk [RR] 1.72, 95% CI 1.19-2.49) and a fasting plasma glucose greater than 8.89 mmol/l ([RR] 1.29, 95 % CI 1.04-1.60), whereas the most important predictors of cardiovascular diseases were insulin-treatment and hypertension. In conclusion, this population-based study showed: 1) slight mortality excess of 35% in Type II diabetes being associated with 2) a 30% increased mortality in subjects with baseline fasting glucose greater than 8.89 mmol/l and 3) a 40% increased risk of death from cardiovascular diseases in hypertensive patients.
Aged↗
Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe.
BACKGROUND: An association between exposure to environmental tobacco smoke (ETS) and lung cancer risk has been suggested. To evaluate this possible association better, researchers need more precise estimates of risk, the relative contribution of different sources of ETS, and the effect of ETS exposure on different histologic types of lung cancer. To address these issues, we have conducted a case-control study of lung cancer and exposure to ETS in 12 centers from seven European countries. METHODS: A total of 650 patients with lung cancer and 1542 control subjects up to 74 years of age were interviewed about exposure to ETS. Neither case subjects nor control subjects had smoked more than 400 cigarettes in their lifetime. RESULTS: ETS exposure during childhood was not associated with an increased risk of lung cancer (odds ratio [OR] for ever exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response relationship could be demonstrated for cumulative spousal ETS exposure. The OR for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible evidence of increasing risk for increasing duration of exposure. No increase in risk was detected in subjects whose exposure to spousal or workplace ETS ended more than 15 years earlier. Ever exposure to ETS from other sources was not associated with lung cancer risk. Risks from combined exposure to spousal and workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma than for adenocarcinoma, but the differences were not statistically significant. CONCLUSIONS: Our results indicate no association between childhood exposure to ETS and lung cancer risk. We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal and workplace ETS. There was no detectable risk after cessation of exposure.
Aged↗
4-Aminobiphenyl-DNA adducts and p53 mutations in bladder cancer.
Epidemiologic studies have suggested that smokers of air-cured tobacco (rich in arylamines) are at higher risk of bladder cancer than smokers of flue-cured tobacco. The risk has been shown to be modulated by the N-acetyltransferase genotype. We analyzed the biopsies of 45 patients with bladder cancer. p53 mutations were sought by direct sequencing, and 4-aminobiphenyl-DNA adducts were measured by negative ion gas chromatography-mass spectrometry. 4-Aminobiphenyl-DNA adducts were higher in smokers of air-cured tobacco and in current smokers, but no relationship with the number of cigarettes smoked was found. Adducts were higher in more advanced histologic grades of tumors. No pattern was evident for p53 mutations. Seven of 9 mutations occurred in grade 3 tumors. No association was found between 4-ABP adducts and GSTM1 or NAT2 genetic polymorphisms.
Adult↗