A Forni

University of Milan, Milano, Lombardy, Italy

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Publications (44)79.96 Total impact

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    ABSTRACT: A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations (chromosome type and chromatid type) are limited. A total of 6,430 healthy individuals from nine laboratories in Croatia, Hungary, Lithuania, Poland, and Slovakia, included in chromosomal aberration surveys performed during 1978-2002, were followed up for cancer incidence or mortality for an average of 8.5 years; 200 cancer cases were observed. Compared with that for the low-tertile level of chromosomal aberrations, the relative risks of cancer for the medium and high tertiles were 1.78 (95% confidence interval: 1.19, 2.67) and 1.81 (95% confidence interval: 1.20, 2.73), respectively. The relative risk for chromosome-type aberrations above versus below the median was 1.50 (95% confidence interval: 1.12, 2.01), while that for chromatid-type aberrations was 0.97 (95% confidence interval: 0.72, 1.31). The analyses of risk of specific cancers were limited by small numbers, but the association was stronger for stomach cancer. This study confirms the previously reported association between level of chromosomal aberrations and cancer risk and provides novel information on the type of aberrations more strongly predictive of cancer risk and on the types of cancer more strongly predicted by chromosomal aberrations.
    American Journal of Epidemiology 02/2007; 165(1):36-43. · 4.78 Impact Factor
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    ABSTRACT: The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.
    Annals of Occupational Hygiene 02/2003; 47(1):37-47. · 2.16 Impact Factor
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    ABSTRACT: An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.
    Cancer Research 04/2000; 60(6):1619-25. · 8.65 Impact Factor
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    ABSTRACT: The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.
    Archive für Toxikologie 12/1999; 73(8-9):431-9. · 5.22 Impact Factor
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    ABSTRACT: Instability in the organization and expression of the genetic material has been hypothesized as the basic mechanism of ageing. To quantify the effect of ageing on chromosomal damage as measured by spontaneous micronuclei (MN) frequency in peripheral blood lymphocytes. Analysis of a large population sample from two laboratories applying the cytokinesis-block technique and a third using traditional interphase analysis. The age-related effect on baseline level of micronuclei frequency and on cell proliferation measures was further investigated in a study of peripheral blood samples from healthy subjects. There was an increase of MN frequency with age. The regression lines showed a positive slope and were statistically significant (P< 0.01) with a steeper trend for cytochalasin B-treated samples. An inverse correlation with age was detected for the percentage of binucleated cells in laboratories using cytochalasin B. This study confirms the increase of basal level of MN with age. A decrease by age in proliferation efficiency measured by the percentage of binucleated cells suggests an interference of age-related factors on cell division. There is an increase in MN frequency with increasing age.
    Age and Ageing 07/1999; 28(4):393-7. · 3.82 Impact Factor
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    ABSTRACT: The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/1998; 405(2):171-8. · 3.90 Impact Factor
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    ABSTRACT: It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.
    Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 02/1998; 154:177-84.
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    ABSTRACT: Clinical, epidemiological and experimental data indicate that inhaled metal dust containing cobalt may produce an interstitial lung disease termed "hard metal disease" (HMD). Some aspects of this pathology such as the lack of correlation with dose exposure, the low frequency of the disease and the presence of T cells in the inflammation site, all suggest the existence of a genetic susceptibility, possibly to an immunological response to cobalt or to self proteins modified by cobalt. Here we report that HMD is strongly associated with residue Glu-69 of the HLA-DP beta chain. All patients, except for one with a rare genotype, possessed this marker as compared to 17 out of 35 exposed unaffected individuals (p = 0.0014). These data allow us to genetically distinguish a subgroup of cobalt-exposed individuals at risk for HMD, independently from the more common allergic reaction.
    European Journal of Immunology 11/1997; 27(10):2741-3. · 4.97 Impact Factor
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    ABSTRACT: Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.
    Cancer Epidemiology Biomarkers &amp Prevention 05/1997; 6(4):249-56. · 4.56 Impact Factor
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    ABSTRACT: Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965-1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations.
    American Journal of Industrial Medicine 04/1997; 31(3):353-60. · 1.97 Impact Factor
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    ABSTRACT: Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965–1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations. Am. J. Ind. Med. 31:353–360, 1997. © 1997 Wiley-Liss, Inc.
    American Journal of Industrial Medicine 02/1997; 31(3):353 - 360. · 1.97 Impact Factor
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    ABSTRACT: Ever-increasing numbers of cancer patients have been treated with antineoplastic drugs in the past few years. Among patients treated with these drugs, an increased risk of a "second neoplasm" has been observed, mainly as a function of increased life expectancy. On the basis of this observation, the International Agency for Research on Cancer has classified a number of antineoplastic drugs as carcinogenic or probably carcinogenic for humans. Various categories of workers are at risk for exposure to antineoplastic drugs, absorbing these substances mainly through inhalation or dermal contact. Although the absorbed doses are notably lower than those administered to patients, review of the literature reveals increased risks of spontaneous abortions and chromosomal aberrations in subjects who have worked without adequate protection. A working group, Prevention of Occupational Risks Due to Handling Antineoplastic Drugs in Health Care, was established by the Italian Institute of Prevention and Safety at Work (Istituto Superiore per la Prevenzione e Sicurezza sul Lavoro-ISPESL) in February 1995. This group reviewed the epidemiologic studies and research on cytogenetic indicators of genotoxicity in occupationally exposed subjects. In addition, the group made recommendations for environmental and biological monitoring of exposure and health surveillance, and developed guidelines for primary and secondary prevention. The group's recommendations are summarized in a consensus document, but cannot be considered definitive, since work practices continue to evolve and will have to be examined further in the future. Thus, more research is needed to achieve answers to the questions raised by the working group. The main topics to be addressed are indicated in the consensus document. In particular, it will be necessary to evaluate working conditions nationwide, using standardized protocols for risk assessment, to achieve precise estimates of workers' exposures.
    International journal of occupational and environmental health 02/1997; 3(1):84. · 1.18 Impact Factor
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    A Forni
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    ABSTRACT: To study the evolution of cytogenetic damage from past exposure to high concentrations of benzene and its health significance, chromosome aberrations (CA) in lymphocytes were reinvestigated after approximately 20 years in four subjects with past severe hemopathy and in seven controls studied in the late 1960s. Increased chromosome-type aberrations were still present up to 30 years after benzene toxicity, but blood counts were normal. The vital status at the end of 1993 was ascertained for 32 subjects with a history of benzene toxicity and for 31 controls studied for CA from 1965 to 1970, who differed significantly for CA rates. Of the 32 benzene-exposed subjects, 1 was lost to follow-up, 20 were still alive, and 11 had died at ages 36 to 83, between 1 and 20 years after the last CA study. Five deaths were from neoplasia (acute erythroleukemia, brain tumor, cancer of lung, paranasal cavity, esophagus). The decreased subjects had significantly higher rates of chromosome-type aberrations than those alive, and those who died of neoplasia had the highest rates of these aberrations in the last study before death or diagnosis of cancer. Out of the 31 controls, 12 had died from 4 to 23 years after the CA study. Three deaths were from neoplasia (two lung cancer, one brain tumor). Even if this is a small sample, the results suggest a higher risk of cancer for the benzene-exposed cohort, who had persistently high CA rates in lymphocytes.
    Environmental Health Perspectives 01/1997; 104 Suppl 6:1309-12. · 7.26 Impact Factor
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    ABSTRACT: Ever-increasing numbers of cancer patients have been treated with antineoplastic drugs in the past few years. Among patients treated with these drugs, an increased risk of a "second neoplasm" has been observed, mainly as a function of increased life expectancy. On the basis of this observation, the International Agency for Research on Cancer has classified a number of antineoplastic drugs as carcinogenic or probably carcinogenic for humans. Various categories of workers are at risk for exposure to antineoplastic drugs, absorbing these substances mainly through inhalation or dermal contact. Although the absorbed doses are notably lower than those administered to patients, review of the literature reveals increased risks of spontaneous abortions and chromosomal aberrations in subjects who have worked without adequate protection. A working group, Prevention of Occupational Risks Due to Handling Antineoplastic Drugs in Health Care, was established by the Italian Institute of Prevention and Safety at Work (Istituto Superiore per la Prevenzione e Sicurezza sul Lavoro-ISPESL) in February 1995. This group reviewed the epidemiologic studies and research on cytogenetic indicators of genotoxicity in occupationally exposed subjects. In addition, the group made recommendations for environmental and biological monitoring of exposure and health surveillance, and developed guidelines for primary and secondary prevention. The group's recommendations are summarized in a consensus document, but cannot be considered definitive, since work practices continue to evolve and will have to be examined further in the future. Thus, more research is needed to achieve answers to the questions raised by the working group. The main topics to be addressed are indicated in the consensus document. In particular, it will be necessary to evaluate working conditions nationwide, using standardized protocols for risk assessment, to achieve precise estimates of workers' exposures.
    Int J Occup Environ Health. 01/1997; 3:84.
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    ABSTRACT: Chromosome aberrations, micronuclei, and sister chromatid exchanges (SCE) were evaluated in cultured lymphocytes of coke oven workers of an Italian steel industry plant, occupationally exposed to polycyclic aromatic hydrocarbons, and in a group of unexposed controls from a non-oven plant in the same area. No differences were found between exposed and controls for rates of total abnormal metaphases (including and excluding gaps), chromatid-type and chromosome-type aberrations, cells with 2 or more breaks, and for micronuclei. On the contrary, SCE were significantly increased in the exposed versus the controls, but, when smoking habits were considered, the increase was significant only for smokers.
    Toxicology Letters 12/1996; 88(1-3):185-9. · 3.15 Impact Factor
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    ABSTRACT: The health surveillance of workers exposed to antineoplastic drugs is based on the fact that these substances are potentially carcinogenic to humans and can cause adverse reproductive effects, as well as irritative and allergic reactions. Health checks must be carried out before starting the job and at periodic intervals thereafter depending on the degree of exposure. These checks will have to evaluate possible physiological and pathological conditions of individual susceptibility. In addition to occupational and pathological history, and physical examination, health surveillance must include tests for the evaluation of hemopoietic, renal and liver functions. Cytogenetic studies on individual workers can be proposed only after documented abnormal exposures to antineoplastic drugs or in case of adverse effects suspected to be caused by this type of exposure.
    La Medicina del lavoro 01/1996; 87(3):265-7. · 0.38 Impact Factor
  • Med Lav. 01/1996; 87(3):194-206.
  • La Medicina del lavoro 01/1996; 87(3):201-206. · 0.38 Impact Factor
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    ABSTRACT: The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.
    Cancer Epidemiology Biomarkers &amp Prevention 10/1995; 4(6):671-9. · 4.56 Impact Factor
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    ABSTRACT: To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.
    Cancer Genetics and Cytogenetics 03/1995; · 1.93 Impact Factor

Publication Stats

973 Citations
79.96 Total Impact Points

Institutions

  • 1988–2007
    • University of Milan
      • • Department of Occupational and Environmental Health
      • • Department of Health Science - DISS
      Milano, Lombardy, Italy
  • 1996–1997
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
  • 1992
    • University of Pavia
      • Department of Internal Medicine and Therapeutics
      Pavia, Lombardy, Italy