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P Vineis

Publications and source records attributed to P Vineis.

At least 19 recordsLinked to original sources

Dietary habits, internal migration and social class in a sample of a northern Italian population.

The study of migrants has generated interesting hypotheses on the etiology of different types of cancer. In particular, it has been suggested that both colon and breast cancer could be related to living conditions, including diet, in the country of immigration. Considerable internal migration occurred in Italy in the sixties. We studied a random sample of 1,400 subjects living in the city of Torino and the province of Varese. They were interviewed with a detailed questionnaire about their dietary habits, and the consumption of several nutrients was considered according to the area of birth and social class. The hypothesis we tested was whether, after controlling for social class, there were different dietary habits among the migrants and the native population, and whether such differences could help in the formulation of etiologic hypotheses on cancer. We found that the intake of saturated fatty acids and cholesterol was lower among the migrants from the south, whereas they consumed higher levels of vegetables than people born in the north. The different intake of saturated fatty acids and cholesterol seemed to be attributable mainly to the consumption of butter, for which the south/north ratio was as low as 0.47 in men and 0.56 in women. Important gradients by social class were also suggested for several nutrients.

Adult

Soft-tissue sarcoma.

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Agricultural Workers' Diseases

The use of biomarkers in epidemiology: the example of bladder cancer.

Epidemiological studies have suggested that genetically based polymorphism for N-acetylation of arylamines might play an important role in the susceptibility to bladder cancer induction. However, these studies show large differences in the extent of such susceptibility. We have undertaken collaborative investigations (with IARC, MIT, NCI and NCTR) which couple internal dosimetry among smokers (measurement of hemoglobin and DNA adducts of arylamines) with the assessment of metabolic polymorphism. In one of these studies, hemoglobin adducts of 14 arylamines (including 2-naphthylamine and 4-aminobiphenyl) were analysed in a group of 86 subjects (smokers and non-smokers) in order to establish whether the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. In another investigation on 100 smokers and non-smokers, metabolic polymorphism for N-acetylatransferase was assessed by measuring five different urinary metabolites of caffeine, after timed urine collection following coffee consumption. Arylamine-hemoglobin adducts were also measured. 4-Aminobiphenyl-hemoglobin adducts were found to be related to both the quantity and the type of tobacco smoked, as well as to the acetylator phenotype (independently of smoking habits).

Aminobiphenyl Compounds

Inter-observer and intra-observer variability of mammogram interpretation: a field study.

To evaluate the performance of radiologists in mammographic mass screening, seven radiologists read blindly the mammograms of 45 women (two views for each breast). The films included 12 normal, 24 benign disease and 9 cancers. The readings were repeated after 2 years. As expected, variability was higher among radiologists than between the two readings of the same radiologist, but general reproducibility was moderate. Kappa values for a positive/negative classification were 0.45 at the first and 0.44 at the second reading (inter-observer comparisons). For the intra-observer comparisons, Kappa values ranged from 0.35 to 0.67 (mean 0.56). Generally, accuracy was low partly due to the difficulty of the cases. A slight increase in sensitivity was observed at the second reading. The level of agreement is a good indicator of accuracy. Proper training and standardization of criteria are essential before mass breast screening is implemented.

Breast Diseases

Substances in human urine that strongly inhibit bacterial mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and related heterocyclic amines.

Extracts of human urine were shown to contain substances that strongly inhibited the liver S9-mediated mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Salmonella typhimurium TA98 strain in a liquid incubation assay. The inhibitory effect was unrelated to cytotoxicity and was similar with urine extracts from smokers and non-smokers. Under similar assay conditions, the mutagenicity of the related amino-imidazoazaarenes, 2-amino-3-methyl-imidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was also found to be strongly inhibited by urine extracts. Decreased or enhanced mutagenicity was seen with 2-acetyl-aminofluorene and 2-aminoanthracene depending on the type of assay, and the time of incubation in liquid medium. A weak inhibition of the mutagenicity of 2-nitrofluorene, a direct-acting mutagen, was observed only after a short incubation time. Mutagenicity of 4-nitroquinoline N-oxide was not altered by the presence of urine extracts at concentrations shown to be inhibitory for the mutagenicity of heterocyclic aromatic amines. Our data suggest that the inhibitory substances in urine act through their capacity to non covalently bind the parent heterocyclic and aromatic amines, thus affecting their availability in aqueous medium for diffusion into liver microsomes where metabolic activation takes place.

Amines

The role of occupational exposure and immunodeficiency in B-cell malignancies. Working Group on the Epidemiology of Hematolymphopoietic Malignancies in Italy.

Excesses of non-Hodgkin's lymphoma have been observed among farmers exposed to phenoxyacetic acid herbicides and, less persuasively, among workers exposed to insecticides. Exposure to organic solvents (particularly chlorinated hydrocarbons) has also been associated with an increased risk of NHL. TCDD (which is a contaminant of phenoxy herbicides), DDT, and chlorinated solvents have all been reported to induce impairment or suppression of cell-mediated immunity. We hypothesize that NHL is caused by common viruses, such as the Epstein-Barr virus, that induce proliferation and immortalization of B-cells, followed by T-cell impairment entailing cell-mediated immunodeficiency. The increased risk of NHL with HIV infection and heart or kidney transplantation, in which immunodeficiency also occurs, is consistent with this hypothesis.

Animals

Validation of a method for the estimation of food portion size.

In the context of the planning phase of a large cohort study on dietary habits and cancer, we have developed a food frequency questionnaire on usual food intake, which includes a set of pictures to estimate the portion size of 23 different dishes. The validity of the estimation of portion size of recently consumed foods has been questioned by other researchers. To validate the use of pictures, we organized a field trial with 103 volunteers. They were invited to a dinner where standard Italian dishes were offered (total 17 foods); all of the portions they chose were recorded and weighed. The following day, we interviewed the volunteers on what they consumed during the dinner, and we compared the weight of the food actually eaten with the weight of the food represented in the pictures. The volunteers overestimated the portion size by more than 20% for six foods and underestimated the portion size by more than 20% for four foods. In addition, we found a tendency toward overestimation of portion size by those who ate smaller portions and underestimation, by those who ate larger portions ("flat slope syndrome").

Adult

Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites.

The wide variations in urinary bladder and colo-rectal cancer incidence in humans have been attributed in part to metabolic factors associated with exposure to carcinogenic aromatic and heterocyclic amines. Cytochrome P-4501A2 (CYP1A2), which catalyses N-oxidation, and acetyltransferase (NAT2) which catalyses N- and O-acetylation, both appear to be polymorphically distributed in human populations; and slow and rapid NAT2 phenotypes have been implicated as risk factors for these cancers. Caffeine has also been shown to undergo 3-demethylation by CYP1A2, and it is further acetylated to 5-acetylamino-6-formylamino-3-methyluracil (AFMU) by the polymorphic NAT2. In this report, we describe a metabolic phenotyping procedure that can be used to determine concomitantly the hepatic CYP1A2 and NAT2 phenotypes. For the NAT2 phenotype, we confirm the valid use of the urinary molar ratio of AFMU/1-methylxanthine, even in alkaline urines. For the CYP1A2 phenotype, the urinary molar ratio of [1,7-dimethylxanthine + 1,7-dimethyluric acid]/caffeine, taken at 4-5 h after caffeine ingestion, was identified from pharmacokinetic analyses of 12 subjects as being better correlated (r = 0.73; p = 0.007) with the rate constant for caffeine 3-demethylation than other previously suggested ratios. This procedure was then used to determine the CYP1A2 phenotype in subjects from Arkansas (n = 101), Italy (n = 95), and China (n = 78). Statistical and probit analyses of nonsmokers indicated that the CYP1A2 activity was not normally distributed and appeared trimodal. This trimodality allowed arbitrary designation of slow, intermediate, and rapid phenotypes, which ranged from 12-13% slow, 51-67% intermediate, and 20-37% rapid, in the different populations. A reproducibility study of 13 subjects over a 5 day or 5 week period showed that, with one exception, intraindividual variability did not alter this CYP1A2 phenotypic classification. Induction of CYP1A2 by cigarette smoking was also confirmed by the increased caffeine metabolite ratios observed in the Arkansas and Italian smokers (blonde tobacco). However, Italian smokers of black tobacco and Chinese smokers did not appear to be induced. Furthermore, probit analyses of Arkansas and Italian blonde tobacco smokers could not discriminate between phenotypes, apparently as a consequence of enzyme induction.

Adult

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Epidemiological studies indicate that subjects of the genetically based slow acetylator phenotype may be at higher risk for bladder cancer than fast acetylators, particularly when they are exposed to carcinogenic arylamines: N-acetylation is a detoxification step in the metabolism of some arylamines. We describe two collaborative studies on tobacco smoking, in which markers of internal dose (arylamine-hemoglobin adducts) and markers of genetically-based metabolic polymorphism have been coupled. In the first investigation, we found that hemoglobin adducts formed by mononuclear arylamines have high reciprocal correlation coefficients, as do adducts from binuclear arylamines. This tendency of adducts with structurally similar arylamines to correlate reciprocally explains a large proportion of the residual variance seen after controlling for smoking habits (number and type of cigarettes). In the second study, the concentration of 4-amino-biphenyl-hemoglobin adducts varied according to three independent determinants: number of cigarettes, type of tobacco (air or flue cured), and acetylator phenotype (slow and fast). The dose-response relationship between the amount of tobacco smoked and level of 4-aminobiphenyl-hemoglobin adducts in the slow acetylators (with an immediate steep increase of the adducts) was different from that in the fast acetylators (with a more regular increase). These findings from "molecular epidemiology" may contribute to an understanding of the role of metabolic polymorphism in human carcinogenesis.

Acetylation

Problems and perspectives in the identification of new occupational carcinogens.

Occupational studies have played a major role in the identification of chemical carcinogens. There still remain, however, substances and occupations that deserve further evaluation. The more careful control of potentially hazardous exposures in most developed countries has necessitated a change in the conduct of epidemiologic investigations. The lowering of exposures and the lack of a simple correspondence between specific exposures and one or a few jobs underscores the need for careful reconstruction of historical exposures. The most successful reconstructions will include the integration of monitoring data, historical information on work histories and work practices, and use of biochemical markers.

Biomarkers

Uses of biochemical and biological markers in occupational epidemiology.

The use of biochemical or biological markers is increasing in cancer epidemiology, but the rationale for their introduction is not always clear, i.e. it has not been established when and how their use is scientifically justifiable, ethically correct and cost-effective. There is an entire range of indications for biomarkers, from the use of very specific measurements aimed at single molecules, to measurements indicating cumulative exposure to agents with the same mechanism of action. The following are some potential uses of markers in occupational epidemiology: 1) exposure assessment in cases in which traditional epidemiologic tools are insufficient (particularly for low doses and low risks; 2) multiple exposures or mixtures, in which the aim is to disentangle the etiologic role of single agents; 3) estimation of the total burden of exposure to chemicals having the same mechanistic target; 4) investigation of pathogenetic mechanisms; 5) study of individual susceptibility (e.g. metabolic polymorphism, DNA repair). Examples are discussed together with methodological limitations.

Biomarkers

The analysis of restriction fragment length polymorphism in human cancer: a review from an epidemiological perspective.

We have reviewed published case-control studies on the role of Restriction Fragment Length Polymorphism (RFLP) for specific loci in the causation of human cancer or as a prognostic factor. Five studies have been published on L-myc polymorphism and prognosis for several types of cancer (lung, kidney, stomach or breast). Sixteen studies report on Ha-ras polymorphism and the risk of cancers in the lung, breast, bladder, colorectum, brain, leukemias and melanoma. The results of the studies are conflicting. In addition, such studies raise important methodological issues: the choice of the cut-off between "rare" and "common" alleles; the inclusion of prevalent cases; the distribution of the alleles in subgroups of the population, including different ethnic groups; a mechanistic interpretation of the role played by the polymorphism, including possible interaction with environmental exposures. These questions need to be answered before a cause-effect relationship can be clearly established.

Gene Frequency

Racial variation in the distribution of Ha-ras-1 alleles.

Restriction fragment length polymorphism analyses of the Ha-ras-1 proto-oncogene were undertaken in white and black populations residing in the Baltimore-Washington metropolitan area to address whether specific rare alleles of the Ha-ras-1 proto-oncogene locus vary in their distribution among different racial groups. High-molecular-weight genomic DNA samples from the lungs of 80 lung cancer patients and 92 accident victims were digested with appropriate restriction enzymes and subjected to Southern analysis using the 6.6-kb BamHI human Ha-ras-1 recombinant fragment from the plasmid pEC. Thirty allelomorphs of different sizes were detected among the 172 study subjects. An association was observed between race and specific alleles. Rare alleles were more frequent in black cancer patients and trauma victims than in whites. Within each racial category, lung cancer patients had an excess of rare alleles. These data indicate the importance of controlling for racial variation when designing studies to determine human cancer risk factors.

Adult

Causality assessment in epidemiology.

Epidemiology relies upon a broad interpretation of determinism. This paper discusses analogies with the evolution of the concept of cause in physics, and analyzes the classical nine criteria proposed by Sir Austin Bradford Hill for causal assessment. Such criteria fall into the categories of enumerative induction, eliminative induction, deduction and analogy. All of these four categories are necessary for causal assessment and there is no natural hierarchy among them, although a 'deductive' analysis of the study design is preliminary to any assessment.

Bayes Theorem

Black (air-cured) and blond (flue-cured) tobacco and cancer risk. I: Bladder cancer.

Four case-control studies in different Latin countries have reported risks of bladder cancer 2-3 times higher for smokers of black (air-cured) than for smokers of blond (flue-cured) tobacco. This observation is interesting in the light of a higher concentration of arylamines in black tobacco. The relative risk dropped very rapidly after discontinuation of smoking, and there was also an effect of age at start, with higher risks associated with earlier onset of the habit. Overall, black tobacco seems to act both on early and late stages of bladder carcinogenesis.

Case-Control Studies