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Biomedical subjects

Paolo Boffetta

Publications and source records attributed to Paolo Boffetta.

At least 73 records · Page 4Linked to original sources
PubMed2005

Reproductive and dietary determinants of the age at menopause in EPIC-Heidelberg.

OBJECTIVES: The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause. METHODS: During follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort in Heidelberg (median duration 5.8 years), 1009 women experienced natural menopause. They were compared to 3798 women who did not experience menopause. Baseline dietary intake was obtained by means of validated food frequency questionnaires. Data on reproductive history and medication was collected by means of questionnaires. Cox' proportional hazard models were applied in order to identify determinants of the age at natural menopause. RESULTS: Increasing age at first full term pregnancy and a longer time interval until occurrences of regular menses are associated with later onset of natural menopause. Compared to never smokers, current smokers have the risk of younger age at menopause. High carbohydrate consumption and high intake of vegetable, fibre and cereal products are inversely related to the age at natural menopause. Women with higher intake of total fat, protein and meat experienced a delayed onset of natural menopause. CONCLUSION: Age at natural menopause is influenced by lifestyle and dietary factors. Further studies including biological markers are needed to clarify these associations.

Adult↗
PubMed2005

Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study.

BACKGROUND: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors. MATERIALS AND METHODS: We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed. RESULTS: A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR=2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR=1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers. DISCUSSION: Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.

Adenocarcinoma↗
PubMed2005

TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers.

TP53 mutations are common in lung cancers of smokers, with high prevalence of G:C-to-T:A transversions generally interpreted as mutagen fingerprints of tobacco smoke. In this study, TP53 (exons 5-9) and KRAS (codon 12) were analyzed in primary lung tumors of never (n = 40), former (n = 27), and current smokers (n = 64; mainly heavy smokers). Expression of p53, cyclooxygenase-2 (Cox-2), and nitrotyrosine (N-Tyr), a marker of protein damage by nitric oxide, were analyzed by immunohistochemistry. TP53 mutations were detected in 47.5% never, 55.6% former, and 77.4% current smokers. The relative risk for mutation increased with tobacco consumption (P(linear trend) < 0.0001). G:C-to-T:A transversions (P = 0.06, current versus never smokers) and A:T-to-G:C transitions (P = 0.03, former versus never smokers) were consistently associated with smoking. In contrast, G:C-to-A:T transitions were associated with never smoking (P = 0.02). About half of mutations in current smokers fell within a particular domain of p53 protein, suggesting a common structural effect. KRAS mutations, detected in 20 of 131 (15.3%) cases, were rare in squamous cell carcinoma compared with adenocarcinoma [relative risk (RR), 0.2; 95% confidence interval (95% CI), 0.07-1] and were more frequent in former smokers than in other categories. No significant differences in Cox-2 expression were found between ever and never smokers. However, high levels of N-Tyr were more common in never than ever smokers (RR, 10; 95% CI, 1.6-50). These results support the notion that lung tumorigenesis proceeds through different molecular mechanisms according to smoking status. In never smokers, accumulation of N-Tyr suggests an etiology involving severe inflammation.

Aged↗
PubMed2005

Occupational X-ray examinations and lung cancer risk.

Occupational X-ray examination programs have been conducted in many countries to screen for occupational and nonoccupational respiratory diseases, resulting in widespread exposure to X-radiation. We conducted a multicentre case-control study of lung cancer in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, including 2,589 cases and 2,859 controls enrolled during 1998-2002. We collected detailed information on occupational X-ray examinations, occupations and tobacco smoking. We calculated odds ratios of lung cancer via multiple logistic regression after adjustment for age, sex, center and tobacco smoking. Among controls 24.9% reported no X-ray examination, 62.9% reported 1-30 examinations and 12.2% reported more than 30 examinations. When we chose individuals with no examination as the reference group, the odds ratios of lung cancer were 1.21 (95% confidence interval [CI] 0.99-1.48), 1.33 (95% CI 1.08-1.64), 1.49 (95% CI 1.18-1.87), 1.52 (95% CI 1.17-1.99) and 2.15 (95% CI 1.50-3.08) for 1-10, 11-20, 21-30, 31-40 and more than 40 examinations, respectively (p-value of test for linear trend <0.0001). The association between X-ray examinations and lung cancer risk was strong in countries with low prevalence of exposure and absent in countries with high prevalence of exposure. Odds ratios for X-ray examinations were lower among smokers than among nonsmokers. The magnitude of the increased risk observed is higher than expected on the basis of other studies of radiation-exposed populations. Although the association we detected between X-ray examinations and lung cancer risk may reflect a carcinogenic effect of repeated exposure to low-level ionizing radiation, reporting bias and particularly uncontrolled confounding by occupational exposure to carcinogens are also likely explanations of the results.

Adult↗
PubMed2005

Risk factors for the development of second primary tumors among men after laryngeal and hypopharyngeal carcinoma.

BACKGROUND: Second primary tumors (SPT) constitute a major threat to the survival of patients with laryngeal carcinoma. However, to the authors' knowledge little is known regarding the risk factors for developing SPTs or about the strategy to be followed to avoid them. METHODS: Eight hundred seventy-six male patients with laryngeal/hypopharyngeal carcinoma enrolled in a population-based, case-control study in 5 centers from South Europe during 1979-1982 were followed up to ascertain the occurrence of SPTs. Standardized incidence ratios were calculated to estimate the risk of SPT occurring in the cohort. Cox proportional hazard models were fitted to estimate the hazard ratio for development of SPTs in relation to use of tobacco smoking, alcohol consumption, and dietary habits before the first primary tumor. RESULTS: One hundred forty-five patients developed an SPT with an annual average rate of 2.1%. An excess risk of developing an SPT of the tongue, mouth, esophagus, and lung was observed. No elevated risks of SPTs were observed in other organs. Alcohol consumption strongly increased the risk of developing an SPT of the upper aerodigestive tract (UADT). Heavy cumulative cigarette smoking increased the risk of developing a lung SPT. A protective effect of high intake of citrus fruit was noticed for SPT in the lung, whereas high butter intake was associated with an increased risk for SPT of the UADT. CONCLUSIONS: Continuous medical surveillance was essential in the UADT and lung to reduce the risk from an SPT after initial laryngeal/hypopahryngeal carcinoma. Alcohol consumption before the first primary tumor was a risk factor for SPT of the UADT. The study suggested a protective role of citrus fruits in the development of a lung SPT.

Adult↗
PubMed2005

Smokeless tobacco use and risk of cancer of the pancreas and other organs.

Limited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco-specific N-nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas.

Adult↗
PubMed2005

Large-scale investigation of base excision repair genetic polymorphisms and lung cancer risk in a multicenter study.

BACKGROUND: Base excision repair (BER) is a highly conserved essential mechanism for maintaining genome integrity. We examined associations among four well-characterized polymorphisms of BER genes (OGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln) and lung cancer risk. METHODS: A total of 2188 patients with lung cancer and 2198 control subjects without lung cancer recruited at 15 centers in six Eastern European countries from February 1998 to October 2002 provided DNA samples for genotype analysis. Genetic polymorphisms were analyzed by the fluorescence 5' exonuclease and Amplifluor assays. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We estimated the false-positive reporting probability (FPRP) for our results by incorporating a range of prior probabilities that specific polymorphisms are associated with lung cancer risk. All statistical tests were two-sided. RESULTS: The overall odds ratio for lung cancer among those with the OGG1 Cys/Cys genotype compared with those with the OGG1 Ser/Ser genotype was 1.34 (95% CI = 0.95 to 1.88); the association was most prominent for adenocarcinoma risk (OR = 1.66, 95% CI = 1.04 to 2.66). Overall, the XRCC1 polymorphisms were not associated with the risk of lung cancer. However, the XRCC1 Arg194Trp and Arg280His variants were each associated with a reduced risk of lung cancer among subjects in the highest quartile of pack-years of smoking compared with common allele homozygotes (ORs of 0.65 [95% CI = 0.46 to 0.93] and 0.56 [95% CI = 0.36 to 0.86], respectively). The associations between the OGG1 Cys/Cys genotype and adenocarcinoma risk and between XRCC1 Arg194Trp polymorphism and lung cancer risk among heavy smokers remained robust given prior probabilities of 25% (FPRP = 0.238) and 10% (FPRP = 0.276), respectively. CONCLUSIONS: Our results do not support a major independent role of BER gene polymorphisms in lung cancer risk. However, we cannot exclude the possibility that the OGG1 Ser326Cys and XRCC1 Arg194Trp polymorphisms play minor roles in lung carcinogenesis.

Adenocarcinoma↗
PubMed2005

Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.

OBJECTIVE: To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. DESIGN: Multicentre, prospective cohort study. SETTING: Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). PARTICIPANTS: 74,607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. MAIN OUTCOME MEASURES: Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. RESULTS: An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). CONCLUSION: The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.

Aged↗
PubMed2005

Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies.

Renal cell carcinoma (RCC) accounts for 3% of adult deaths from cancer. The risk factors for its development are still under intense investigation. Although tobacco smoke is a risk factor, the data are inconsistent and the extent of the increased risk is unclear. Estimates from 19 case-control and 5 cohort studies were used. The case-control reports included 8,032 cases and 13,800 controls; the cohort estimates were based on 1,457,754 participants with 1,326 cases of RCC. The relative risk (RR) for RCC for ever smokers as compared to lifetime never smokers was 1.38 (95% confidence interval [CI] = 1.27-1.50). The RR for male smokers was 1.54 (95% CI = 1.42-1.68) and for female smokers was 1.22 (95% CI = 1.09-1.36). For men and women there was a strong dose-dependent increase in risk. Ever smoker men who had smoked 1-9, 10-20 or 21 or more cigarettes/day had a RR of 1.60 (95% CI = 1.21-2.12), 1.83 (95% CI = 1.30-2.57), or 2.03 (95% CI = 1.51-2.74), respectively. For women, the relative risks were 0.98 (95% CI = 0.71-1.35), 1.38 (95% CI = 0.90-2.11), or 1.58 (95% CI = 1.14-2.20), respectively. The advantages of smoking cessation were confirmed by a reduction in RR for those who had quit smoking for >10 years as compared to those who had quit for 1-10 years. Inhaled tobacco smoke is clearly implicated in the etiology of RCC, with a strong dose-dependent increase in risk associated with numbers of cigarettes smoked per day and a substantial reduction in risk for long-term former smokers.

Adult↗
PubMed2005

Occupational exposures and risk of esophageal and gastric cardia cancers among male Swedish construction workers.

OBJECTIVE: The rising incidence and the strong male predominance among patients with esophageal and gastric cardia adenocarcinoma remain unexplained. We hypothesized that occupational airborne exposures in a traditional male dominated industry might contribute to these observations. METHODS: A prospective, large cohort study of Swedish construction workers was linked to the Swedish population-based registers of Cancer, Causes of Death and Total Population. 260,052 men were followed from 1971 through 2000. Industrial hygienists assessed specific exposures for 200 job titles, and occupational airborne exposures were analyzed separately and combined. Incidence rate ratios (IRR), with 95% confidence intervals (CI), were estimated in multivariable Cox regression models adjusted for attained age, calendar period, smoking status and body mass. RESULTS: We found positive associations between high exposure to asbestos (IRR 4.5 [95% CI 1.4-14.3]) and cement dust (IRR 3.8 [95% CI 1.5-9.6]) and risk of esophageal adenocarcinoma. Associations were seen between high exposure to asphalt fumes (IRR 2.3 [95% CI 1.0-5.3]) and wood dust (IRR 4.8 [95% CI 1.2-19.4]) and risk of cardia adenocarcinoma. No consistent associations regarding esophageal squamous-cell carcinoma were found. CONCLUSIONS: Exposure to asbestos and cement dust may be risk factors for esophageal adenocarcinoma, and exposure to asphalt fumes and wood dust may increase the risk of cardia adenocarcinoma. However, these associations cannot explain the major sex differences or the increasing incidence trends of these tumors.

Adenocarcinoma↗
PubMed2005

Occupational exposures and risk of adenocarcinoma of the lung in Uruguay.

OBJECTIVES: To investigate occupational risks of lung adenocarcinoma in Uruguay and to confirm a previously reported increased risk among butchers. METHODS: We conducted a case-control study among men in four major hospitals in Montevideo, based on interviews to 338 cases of lung adenocarcinoma and 1014 hospital-based controls. We calculated odds ratios (ORs) of lung adenocarcinoma for employment in 22 jobs, after adjustment for tobacco smoking and other potential confounders. RESULTS: The OR was increased for employment as farmer, tractor driver, painter and medical worker, but no trend was suggested for duration of employment. Long-term employment as mason, glass worker or textile worker resulted in an increased OR. The OR for employment as butcher was 1.2 (95% confidence interval 0.7-2.1). The OR increased with increasing duration of self-reported exposure to formaldehyde. CONCLUSIONS: Occupational exposures seem to play a limited role in causing lung adenocarcinoma among men in Uruguay. Employment as butcher was not confirmed as an important risk factor.

Adenocarcinoma↗
PubMed2005

Squamous and small cell carcinomas of the lung: similarities and differences concerning the role of tobacco smoking.

In the time period 1988-2000, a case-case study on environmental factors and lung cancer risk was conducted in Montevideo, Uruguay. This study was designed in order the establish possible differences between squamous cell carcinomas (SCC) and small cell carcinomas (SCLC) of the lung in relation to tobacco smoking. Three hundred and ninety one (391) patients with small cell carcinoma were compared with 1187 patients with squamous cell carcinoma. Regarding sex, the study included a small number of women (26 with SCLC and 20 with SCC). SCLC was associated with higher risks for smoking status, smoking intensity and cumulative exposure to tobacco smoking when compared with SCC. These three tobacco variables were significantly different between both cell types in men. Smoking duration was significantly higher among SCLC compared with SCC only in women. With decreasing age at starting to smoke, the proportion of SCLC increases at the expense of SCC. Finally, types of tobacco and cigarette were not different between cell types in both sexes. It should be noted that these tobacco variables were not associated with increased risks among SCC, when this cell type was compared with SCLC. These results suggests that SCLC display the strongest relation with tobacco smoking than SCC.

Adult↗
PubMed2005

Comparison of two statistical approaches to predict all-cause mortality by dietary patterns in German elderly subjects.

Dietary patterns are comprehensive variables of dietary intake appropriate to model the complex exposure in nutritional research. The objectives of this study were to identify dietary patterns by applying two statistical methods, principal component analysis (PCA) and reduced rank regression (RRR), and to assess their ability to predict all-cause mortality. Motivated by previous studies we chose percentages of energy from different macronutrients as response variables in the RRR analysis. We used data from 9356 German elderly subject enrolled in the European Prospective Investigation into Cancer and Nutrition study. The first RRR pattern, subjects which explained 30.8 % of variation in energy sources and especially much variation in intake of saturated fat, monounsaturated fat and carbohydrates was a significant predictor of all-cause mortality. The pattern score had high positive loadings in all types of meat, butter, sauces and eggs, and was inversely associated with bread and fruits. After adjustment for other known risk factors, the relative risks from the lowest to highest quintiles of the first RRR pattern score were 1.0, 1.01, 0.96, 1.32, 1.61 (P for trend: 0.0004). In contrast, the first two PCA patterns explaining 19.7 % of food intake variation but only 7.0 % of variation in energy sources were not related to mortality. These results suggest that variation in macronutrients is meaningful for mortality and that the RRR method is more appropriate than the classic PCA method to identify dietary patterns relevant to mortality.

Aged↗
PubMed2005

Dietary patterns among older Europeans: the EPIC-Elderly study.

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.

Age Distribution↗
PubMed2005

Polycyclic aromatic hydrocarbons and fatal ischemic heart disease.

BACKGROUND: Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure-response relation has not been demonstrated. METHODS: We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. RESULTS: Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m or higher, for which the relative risk was 1.64 (95% confidence interval=1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. CONCLUSIONS: Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association.

Cause of Death↗