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Paolo Boffetta

Publications and source records attributed to Paolo Boffetta.

At least 109 records · Page 6Linked to original sources
PubMed2004

Risk of acute myeloid leukemia after exposure to diesel exhaust: a review of the epidemiologic evidence.

The objective of this study was to review the epidemiologic literature on exposure to diesel exhaust (DE) exposure and leukemia risk. No cohort studies, nine case-control studies, and nine studies based on routine statistics and record linkages provided results useful to assess the risk of leukemia, and in particular acute myeloid leukemia (AML), among exposed workers. No formal pooling of the results was possible. The available studies do not consistently suggest an increased risk of leukemia, and specifically AML, among workers exposed to DE. For none of the occupational groups potentially exposed to DE, the results suggest an association, and sporadic positive results are counterbalanced by negative associations and might result from reporting bias. DE exposure does not appear to be associated with increased risk of leukemia.

Age Distribution↗
PubMed2004

Exon 5 polymorphisms in the O6-alkylguanine DNA alkyltransferase gene and lung cancer risk in non-smokers exposed to second-hand smoke.

PURPOSE: The objective of the study was to examine the association of three exon 5 variants in the O(6)-alkylguanine DNA alkyltransferase (AGT) gene involved in the repair of the mutagenic DNA lesion O(6)-alkylguanine formed by nitrosamines, with lung cancer risk in never-smokers. EXPERIMENTAL DESIGN: Exon 5 of the AGT gene was sequenced in genomic DNA from 136 cases and 133 hospital- or population-based controls for whom questionnaire information on second-hand smoke and diet was available to determine the frequencies of the Gly(160)Arg, Ile(143)Val, and Lys(178)Arg variant alleles. RESULTS: No codon (160)Arg variant alleles were found in the study population. The codon (143)Val and (178)Arg variant alleles, present at allele frequencies of 0.07, showed 100% linkage. The odds ratio (OR) of lung cancer for these variant carriers was 2.05 [95% confidence interval (CI) 1.03-4.07]. The risk varied between the different lung cancer pathologies with an increased risk for adenocarcinoma (OR 2.67, 95% CI 1.21-5.87) or small cell carcinoma (OR 4.83, 95% CI 0.91-25.7) but not for squamous cell carcinoma (OR 1.07, 95% CI 0.27-4.18). Compared with individuals carrying the mutant alleles unexposed to second-hand smoke, the OR for exposed variant carriers was 1.95 (95% CI 0.53-1.15); a similar interaction, although not significative, was observed for low consumption of cruciferous vegetables and for green vegetables and tomatoes. CONCLUSIONS: These results point toward a role of AGT polymorphisms in lung cancer susceptibility among never-smokers, in particular among subjects exposed to environmental carcinogens.

Adenocarcinoma↗
PubMed2004

Applying new biotechnologies to the study of occupational cancer--a workshop summary.

As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk.

Biomarkers↗
PubMed2004

Listing occupational carcinogens.

The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis.

Carcinogens↗
PubMed2004

Cancer incidence of Nordic asphalt workers.

OBJECTIVES: The aim of the study was to investigate cancer risk following employment in the asphalt industry. METHODS: Cancer incidence was studied among 22 362 male asphalt workers employed for more than one season in jobs entailing exposure to bitumen (mainly road pavers) in Denmark, Finland, Norway, and Sweden. These workers are part of a European cohort of asphalt workers, for which results on mortality have been reported. The follow-up was almost complete, and reference rates were obtained from national cancer registries. RESULTS: The incidence of cancer was reduced in all four countries [overall standardized incidence ratio (SIR) 0.89, 95% confidence interval (95% CI) 0.86-0.94]. Lung cancer incidence was increased in all four countries, yielding an overall SIR of 1.21 (95% CI 1.07-1.36), but no trend was detected according to time since first employment. No overall increased incidence of bladder cancer was observed, but there was a suggestion of a tendency towards higher risk with longer time since first employment, with a relative risk of 1.85 (95% CI 0.90-3.78) for more than 30 years versus 1-14 years (P-value for trend 0.1). The incidence of lip and stomach cancer was nonsignificantly increased, and the excess was present mainly in Denmark. No increased incidence was detected for other neoplasms, notably malignant melanoma, nonmelanoma skin cancer, and kidney cancer. CONCLUSIONS: The results of this study confirm the pattern of cancer risk detected in the mortality analysis of the European cohort; in addition, they provide suggestive evidence of an excess risk of bladder cancer among asphalt workers.

Adolescent↗
PubMed2004

Multiple primary cancers as clues to environmental and heritable causes of cancer and mechanisms of carcinogenesis.

Successes in cancer therapy are leading to an increasing incidence of second cancers, which may be due to the same factors that cause first cancers or to the effect of therapy for the first cancer. There are also a number of specific methodological and sampling problems that have to be controlled before informative studies can be embarked upon. The risk of a second cancer is higher than that for the first one, which may be an indication of a particular exposure, an inherited set of genes, or both. We show clustering of multiple cancers caused by tobacco, alcohol and infections. We discuss familial aggregation of cancer as one of the causes of multiple primary cancers. However, multiple primary cancers may particularly be a manifestation of polygenic susceptibility, which cannot easily be recognized as familial clustering, and multiple cancers may offer a model for understanding the complex etiology of human cancer and for generating and testing hypotheses on mechanisms of carcinogenesis.

Animals↗
PubMed2004

Mechanistic considerations in the molecular epidemiology of head and neck cancer.

Head and neck cancer occurs through a complex multistage process that is likely to involve a combination of carcinogen exposure and genetic susceptibility. The primary cause of head and neck cancer are alcohol consumption and cigarette smoking, although the carcinogenic mechanism for these agents is unclear. Molecular epidemiological studies of head and neck cancer can help to clarify the carcinogenic process in several ways, including identification of metabolizing genes which increase the risk of head and neck cancer, identification of DNA adducts in target cells and analysis of specific gene mutations and their relationship with exposure. This review summarizes current knowledge on the molecular epidemiology of head and neck cancer and attempts to identify those areas where future studies may prove fruitful.

Alcohol Drinking↗
PubMed2004

Using hierarchical modeling in genetic association studies with multiple markers: application to a case-control study of bladder cancer.

BACKGROUND: Genetic association studies are generating much information, usually in the form of single nucleotide polymorphisms in candidate genes. Analyzing such data is challenging, and raises issues of multiple comparisons and potential false-positive associations. Using data from a case-control study of bladder cancer, we showed how to use hierarchical modeling in genetic epidemiologic studies with multiple markers to control overestimation of effects and potential false-positive associations. METHODS: The data were first analyzed with the conventional approach of estimating each main effect individually. We subsequently employed hierarchical modeling by adding a second stage (prior) model that incorporated information on the potential function of the genes. We used an empirical-Bayes approach, estimating the residual effects of the genes from the data. When the residual effect was set to zero, we instead used a semi-Bayes approach, in which they were pre-specified. We also explored the impact of using different second-stage design matrices. Finally, we used two approaches for assessing gene-environment interactions. The first approach added product terms into the first-stage model. The second approach used three indicators for subjects exposed to gene-only, environment-only, and both genetic and environmental factors. RESULTS: By pre-specifying the prior second-stage covariates, the estimates were shrunk to the mean of each pathway. The conventional model detected a number of positive associations, which were reduced with the hierarchical model. For example, the odds ratio for myeloperoxidase (G/G, G/A) genotype changed from 3.17 [95% confidence interval (CI), 1.32-7.59] to 1.64 (95% CI, 0.81-3.34). A similar phenomenon was observed for the gene-environment interactions. The odds ratio for the gene-environment interaction between tobacco smoking and N-acetyltransferase 1 fast genotype was 2.74 (95% CI, 0.68-11.0) from the conventional analysis and 1.24 (95% CI, 0.80-1.93) from the hierarchical model. CONCLUSION: Adding a second-stage hierarchical modeling can reduce the likelihood of false positive via shrinkage toward the prior mean, improve the risk estimation by increasing the precision, and, therefore, represents an alternative to conventional methods for genetic association studies.

Arylamine N-Acetyltransferase↗
PubMed2004

Reliability and validity of opiate use self-report in a population at high risk for esophageal cancer in Golestan, Iran.

OBJECTIVE: To assess the reliability and validity of self-reported opium use in a rural Iranian population at high risk for esophageal cancer in preparation for a large cohort study. METHOD: 1,057 subjects ages 33 to 84 years were recruited from Gonbad city and three surrounding villages in Golestan province of Iran and completed a questionnaire and provided biological samples. The history and duration of using opium, smoking tobacco, chewing nass, and drinking alcohol were measured by questionnaire in the entire cohort. A subgroup of 130 people was reinterviewed after 2 months to assess reliability. Validity of the opium question was assessed by comparing the questionnaire responses with the presence of codeine and morphine in the urine of 150 selected subjects. RESULTS: Self-reported opiate use is reliable and valid in this population. The reliability of ever opium use and duration of opium use had kappa's of 0.96 and 0.74, respectively. The validity of self-reported opium use was also high. Using urine codeine or morphine as the gold standard for use of opium, self-report had a sensitivity of 0.93 and a specificity of 0.89. CONCLUSIONS: The self-reported use of opium can provide a reliable and valid measurement in this population and will be useful for studying associations between opium use and occurrence of esophageal cancer and other diseases.

Adult↗
PubMed2004

Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis.

The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile-->Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.

Acyltransferases↗
PubMed2003

Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India.

In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered.

Adult↗
PubMed2003

Russian mortality trends for 1991-2001: analysis by cause and region.

OBJECTIVES: To investigate trends in Russian mortality for 1991-2001 with particular reference to trends since the Russian economic crisis in 1998 and to geographical differences within Russia. DESIGN: Analysis of data obtained from the Russian State statistics committee for 1991-2001. All cause mortality was compared between seven federal regions. Comparison of cause specific rates was conducted for young (15-34 years) and middle aged adults (35-69 years). The number of Russian adults who died before age 70 in the period 1992-2001 and whose deaths were attributable to increased mortality was calculated. MAIN OUTCOME MEASURES: Age, sex, and cause specific mortality standardised to the world population. RESULTS: Mortality increased substantially after the economic crisis in 1998, with life expectancy falling to 58.9 years among men and 71.8 years among women by 2001. Most of these fluctuations were due to changes in mortality from vascular disease and violent deaths (mainly suicides, homicides, unintentional poisoning, and traffic incidents) among young and middle aged adults. Trends were similar in all parts of Russia. An extra 2.5-3 million Russian adults died in middle age in the period 1992-2001 than would have been expected based on 1991 mortality. CONCLUSIONS: Russian mortality was already high in 1991 and has increased further in the subsequent decade. Fluctuations in mortality seem to correlate strongly with underlying economic and societal factors. On an individual level, alcohol consumption is strongly implicated in being at least partially responsible for many of these trends.

Adolescent↗
PubMed2003

Mortality from obstructive lung diseases and exposure to polycyclic aromatic hydrocarbons among asphalt workers.

Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

Causality↗
PubMed2003

Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men.

Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case-control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose-response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26-5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07-5.22) and 2.83 (95% CI 2.18-3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42-4.64) and that of esophageal cancers was 3.41 (95% CI 1.46-7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2-4 years before the interview.

Adult↗
PubMed2003

Meta-analysis of social inequality and the risk of cervical cancer.

Previous studies of the relationship between socio-economic status and cervical cancer have been mainly based on record linkage of routine data, such as cancer registry incidence rates and regional measures of social class based on census data. These routine data are liable to substantial misclassification with respect to socio-economic status. Previous reports are also primarily from developed countries, whereas the major burden of cervical cancer is in developing countries. We have therefore pooled the data from previously reported case-control studies of cervical cancer or dysplasia, which contain individual-level information on socio-economic characteristics to investigate the relationship between cervical cancer, social class, stage of disease, geographical region, age and histological type. Based on 57 studies, we found an increased risk of approximately 100% between high and low social class categories for the development of invasive cervical cancer, and an increased risk of approximately 60% for dysplasia, including carcinoma in situ. Although the difference was observed in all countries, it was stronger in low/middle income countries and in North America than in Europe. No clear differences were observed between squamous cell carcinoma and adenocarcinoma, or between younger and older women. These results indicate that both cervical infection with human papillomavirus, which is linked to both female and male sexual behaviour, and access to adequate cervical cancer screening programmes are likely to be important in explaining the large cervical cancer incidence rates observed in different socio-economic groups, and that the importance of these factors may vary between different geographical regions.

Adult↗
PubMed2003

Epidemiologic study of cancer mortality among Israeli asphalt workers.

BACKGROUND: We describe the results of a cancer mortality study among asphalt workers in Israel. METHODS: Personal identifiers and employment histories of 2,176 workers were extracted from company records. RESULTS: Mortality from all malignant neoplasms was significantly reduced in the whole cohort (SMR 0.68, 95% confidence interval (CI) 0.56-0.83). SMR for lung cancer was elevated in workers exposed to bitumen (SMR 1.05, 95% CI 0.62-1.66). No significant elevation or reduction in mortality was observed in relation to a specific site. SMRs for lung cancer was higher among ever exposed to bitumen than among unexposed. There was no association between lung cancer risk and estimated exposure to bitumen fume, and no dose-response was apparent. CONCLUSIONS: While the results of this cohort study indicate a slightly increased SMR for lung cancer, it did not produce evidence of a causal link between lung cancer and exposure to bitumen fume.

Adult↗
PubMed2003

Cohort mortality study among French asphalt workers.

BACKGROUND: In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. METHODS: Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. RESULTS: Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. CONCLUSIONS: Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn.

Adult↗