Showing papers by "Frederica P. Perera published in 2007"

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

Abstract: The purpose of this review is to evaluate progress in molecular epidemiology over the past 24 years in cancer etiology and prevention to draw lessons for future research incorporating the new generation of biomarkers. Molecular epidemiology was introduced in the study of cancer in the early 1980s, with the expectation that it would help overcome some major limitations of epidemiology and facilitate cancer prevention. The expectation was that biomarkers would improve exposure assessment, document early changes preceding disease, and identify subgroups in the population with greater susceptibility to cancer, thereby increasing the ability of epidemiologic studies to identify causes and elucidate mechanisms in carcinogenesis. The first generation of biomarkers has indeed contributed to our understanding of risk and susceptibility related largely to genotoxic carcinogens. Consequently, interventions and policy changes have been mounted to reduce risk from several important environmental carcinogens. Several new and promising biomarkers are now becoming available for epidemiologic studies, thanks to the development of high-throughput technologies and theoretical advances in biology. These include toxicogenomics, alterations in gene methylation and gene expression, proteomics, and metabonomics, which allow large-scale studies, including discovery-oriented as well as hypothesis-testing investigations. However, most of these newer biomarkers have not been adequately validated, and their role in the causal paradigm is not clear. There is a need for their systematic validation using principles and criteria established over the past several decades in molecular cancer epidemiology.

Relationship between Polycyclic Aromatic Hydrocarbon–DNA Adducts, Environmental Tobacco Smoke, and Child Development in the World Trade Center Cohort

Abstract: In this research we focused on possible neurodevelopmental risks of prenatal exposure to pollutants emitted by the World Trade Center (WTC) fires because of prior experimental and human evidence that some of the pollutants can affect the developing brain and adversely affect cognitive development (Perera et al. 2006; Wormley et al. 2004). Of interest were possible interactions between polycyclic aromatic hydrocarbons (PAHs) (measured here by benzo[a]pyrene [BaP]–DNA adducts in cord blood) and prenatal environmental tobacco smoke (ETS) exposure, as was previously seen for fetal growth in this same cohort (Perera et al. 2005). The destruction and combustion of the WTC towers released a complex mixture of toxicants into the New York City environment on and after 11 September 2001 (Lioy et al. 2002; McGee et al. 2003; Offenberg et al. 2003). These included pollutants with neurodevelopmental toxicity and carcinogens such as PAHs, poly-chlorinated biphenyls (PCBs), polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polybrominated diphenyl ethers, and various metals (Chen and Thurston 2002; Jeffrey et al. 2003; Lioy et al. 2002; McKinney et al. 2002; Offenberg et al. 2003). The WTC plume contained high levels of PAHs that spiked at a measurement site 1.8 km (1.1 mile) northeast of the WTC site several times in September and October 2001, with a peak on 3 October during an inversion that brought smoke back to ground level (Service 2003). PAHs are also common pollutants in urban air from fossil fuel combustion by motor vehicles, residential heating units, power plants, and industrial activities (Bostrom et al. 2002) and are present in tobacco smoke and in grilled or broiled food (International Agency for Research on Cancer 1983; U.S. Environmental Protection Agency 1990). Thus, during the weeks and months after 11 September 2001, the WTC fires added to an ongoing background exposure to airborne PAHs. Several PAHs, including BaP (Bapat et al. 1994), are known human mutagens, carcinogens, and/or developmental toxicants. BaP is widely used as a representative PAH because concentrations of individual PAHs in the urban setting are highly intercorrelated (Perera et al. 2003). Therefore, we have used BaP–DNA adducts as a proxy for PAH–DNA adducts. Because they reflect individual variation in exposure, absorption, metabolic activation, and DNA repair, the adducts in white blood cells provide a biologic dosimeter and marker of potential risk (Bartsch and Hietanen 1996; Veglia et al. 2003). DNA adducts have an estimated half-life of 3–4 months (Mooney et al. 1995). Thus, considering that the main exposure to WTC-related PAHs occurred between 11 September 2001 and 11 November 2001 while the fires were ongoing, adduct measurements in blood samples collected between December 2001 and June 2002 would partly reflect that exposure. Here we focus on possible risks of the WTC disaster to children of women who were pregnant at that time because of evidence that the fetus is more sensitive than the adult to a range of pollutants including PAHs (National Research Council 1993; Perera et al. 2004; Whyatt et al. 2001). For example, compared with their mothers, newborns sampled at delivery have more genetic damage (in the form of DNA adducts) per estimated unit of exposure to PAHs; and they demonstrate slower clearance of various toxicants (National Research Council 1993; Perera et al. 2004; Whyatt et al. 2001). Our previous findings in this cohort raised some concern about possible neurodevelopmetal effects of PAHs from the WTC event. First, we found that PAH–DNA adducts were highest among those mothers and newborns in the cohort who had at some time in the 4 weeks after 11 September 2001 resided within 1 mile of the WTC site; adduct levels were intermediate among those who worked but did not live within 1 mile of the WTC during this time period; and they were lowest among those who neither worked nor lived within this radius (Perera et al. 2005). Second, we observed a significant interaction between cord adducts treated as a continuous variable and maternal prenatal ETS exposure on birth weight (p = 0.03) and head circumference (p = 0.04) (Perera et al. 2005). These findings suggested the need for follow-up of the children, because other research has found associations between reduced birth weight, even in the normal range, and health and developmental problems (Barker 1996; Dietz 1994; Matte et al. 2001; Rice and Barone 2000; Richards et al. 2002). Therefore, we examined the relationships between PAH–DNA adducts measured in umbilical cord blood, prenatal ETS exposure, and neurodevelopmental outcomes at 3 years of age in a subset of the WTC cohort who have been prospectively followed through that time point.

A bibliometric analysis of scientific production in cancer molecular epidemiology

Abstract: Objectives: The main purpose of this research was to compare thescientificproductioninthefieldofcancer molecularepidemiologyamong countries and to evaluate the publication trend between1995 and 2004. Methods: A bibliometric study was carried outsearching the PubMed database with a combined search strategybased on the keywords listed in the medical subject headings anda free text search. Only articles from a representative subset of92journals—accountingfor80%ofpapersidentified—wereselectedfor the analysis, and the resulting 13 240 abstracts were manuallychecked according to a list of basic inclusion criteria. The studyevaluatedthenumberofpublicationsandtheimpactfactor(meanand sum), absolute and normalized by country population andgross domestic product. Results: A total of 3842 citations werefinally selected for the analysis. Thirty-seven percent came fromthe European Union (UK, Germany, Italy, France and Swedenranking at the top), 31.6% from USA and 9.7% from Japan.The highest mean impact factor was reported for Canada (6.3),USA (5.9),Finland (5.8)andUK (5.2).Finland,Sweden andIsraelhad the best ratio between scientific production and availableresources. ‘Genetic polymorphism, glutathione transferase,breast neoplasm, risk factors, case–control studies and polymer-ase chain reaction’ were the most used keywords in each of thesubgroups evaluated, although inclusion criteria may have privi-leged studies dealing with exogenous carcinogens. Conclusion:Cancer molecular epidemiology is an expanding area attractinganincreasinginterest.Theidentificationofanoperativedefinitionisanecessaryconditiontogivetothisdisciplineauniquescientificidentity.IntroductionScientists have long recognized the intrinsic limitations of the tradi-tional epidemiological design to discern the causal link between riskfactors and disease occurrence in this evolving society. The pressingneed of developing new tools for etiologic research was the drivingforce that in 1982 moved Perera and Weinstein to propose an enhance-ment of the epidemiological approach through ‘the incorporation oflaboratory analytical techniques to elucidate the biochemical or mo-lecular basis of disease etiology’ (1). Since then, many studies havebeen conducted to investigate the distribution of diseases in humanpopulations and their determinants, incorporating molecular biologytechniques into the epidemiologic design (2–4).In the last decades, molecular epidemiology has gained a well-established position in the field of cancer research, with a numberof dedicated researchers and institutions all over the world. This in-creased popularity has resulted in a growing scientific production,whose impact in the field is still to be fully quantified. Bibliometricstudies are systematically conducted to evaluate the amount and theevolution of the scientific production among countries in major bio-medical fields (5–12), but are particularly useful for novel disciplines,whose impact on the larger field of biomedical research has yet to befully evaluated.Bibliometry surveys the scientific production of a scientist, a re-search unit, an institution or a country by taking into consideration thehistorical development of a discipline or by quantifying its role in thedomain of science, or prospectively, identifying research fronts. Toperform this evaluation, citation analysis is currently used.Citation analysis is defined as the number of times an article is citedas a reference in other articles and is based on the general assumptionthat the number of citations reflects an article’s influence and notorietyand, hence, its quality. The databases most commonly used are thoseproduced by the Thomson Scientific (formerly known as ThomsonInstitute for Scientific Information), which evaluates the papers pub-lished in .7500 peer-reviewed journals in the sciences and socialsciences, and each year publishes an index (Journal Citation Reports)based on cited articles (13).The main purpose of this paper is to provide a report on the scien-tific production in the field of cancer molecular epidemiologyamong countries. To this aim, the geographical distribution and thetemporal trend of papers published between 1995 and 2004 have beeninvestigated.Basic information about published papers includes the list of thosejournals most often chosen by researchers in the field and furtherconsideration was given to the impact factor (IF) of the journals wherethe papers were published. This parameter gives further informationabout the quality of the published material, especially if evaluated inthe context of major socioeconomic variables, i.e. the source countrypopulation and its gross domestic product (GDP).Finally, the evaluation of most frequently used keywords in cancermolecular epidemiology papers provided useful hints about the iden-tification of main research trends and helped to interpret the perspec-tive of evolution of this field.Methods

Fish Intake During Pregnancy and Mercury Level in Cord and Maternal Blood at Delivery: An Environmental Study in Poland

Abstract: Objectives: The purpose of this study was to estimate the amount of absorbed mercury (Hg) by mothers and their infants as a result of fish consumption during pregnancy. Materials and Methods: The cohort consisted of 313 mother-infant pairs recruited initially from ambulatory prenatal clinics in the first and second trimesters of pregnancy. The customary pattern of fish consumption during pregnancy reported by mothers was correlated with Hg levels in cord and maternal blood at delivery. Blood Hg level was measured using atomic absorption spectrometry. Results: The mean Hg concentration in cord blood was markedly higher than in maternal blood at delivery (1.09 μg/L; 95%CI: 1.00-1.13 μg/L vs. 0.83 μg/L; 95%CI: 0.76-0.91 μg/L). There was significant correlation (r S = 0.62, 95%CI: 0.55-0.69) between Hg levels in cord and maternal blood. The overall ratio of Hg in cord blood vs. maternal blood was 1.7 (95%C: 1.50-1.89). Fish consumed during the last pregnancy trimester correlated stronger with umbilical cord Hg concentrations (r S = 0.32; 95%CI: 0.22-0.40) than with Hg in maternal blood (r S = 0.23; 95%CI: 0.14-0.33). Conclusions: The study shows that in Poland, babies are exposed to moderate levels of mercury prior to birth and that fish eating in pregnancy significantly contributes to prenatal Hg exposure. The findings also suggest that the level of cord blood Hg should not be used for describing inter-individual differences in maternal exposure to Hg compounds unless a proper correction factor is introduced.

Pre-pregnancy dietary vitamin A intake may alleviate the adverse birth outcomes associated with prenatal pollutant exposure: epidemiologic cohort study in Poland.

Abstract: A cohort study assessed the relationship between dietary intake of vitamin A in 493 healthy mothers before and around conception and adverse birth outcomes associated with environmental toxicant exposures. The cohort, non-smoking women with singleton pregnancies, aged 18-35 years, gave birth at 34-43 weeks of gestation. The women were asked about their diets over one year preceding pregnancy. Measurements of PM2.5 were carried out during the second trimester. Birth outcomes were adjusted for potential confounding factors, including gestational age. Standardized beta regression coefficients confirmed an inverse association between PM2.5 and birth weight (beta = -172.4, p = 0.02), but the effect of vitamin A on birth weight was positive (beta = 176.05, p = 0.05), when the two were adjusted for each other. The negative effect of higher prenatal PM2.5 exposures (above third tertile) on birth weight was significant in women below the third tertile of vitamin A intakes (beta = -185.1, p = 0.00), but not in women with higher intakes (beta = 38.6, p = 0.61). The negative effect of higher PM2.5 exposure on length at birth was significant with lower vitamin A intakes (beta = -1.1, p = 0.00) but not with higher intakes (beta = -0.3, p = 0.56). Prepregnancy nutrition of mothers may modulate the harmful effects of prenatal exposures to pollutants on birth outcomes.

Personal Exposure to Fine Particles and Benzo[A]pyrene. Relation with Indoor and Outdoor Concentrations of these Pollutants in Kraków

Abstract: Objectives This study assessed personal exposure of pregnant women to fine particles (PM(25)) and benzo[a]pyrene (B[a]P) and the relationship between pollutant concentrations in ambient and indoor air Materials and methods In a group of 78 pregnant women, simultaneous 48 h measurements of personal, indoor, and outdoor exposure to PM(25) and B[a]P were carried out in the second trimester of pregnancy The results show that participants were exposed to varying concentrations of PM(25) and B[a]P, with higher exposure in the winter season Overall, the mean personal PM(25) level was 304 microg/m(3) and B[a]P 21 ng/m(3) The winter/summer ratios for mean personal exposures were 14 (356 microg/m(3) vs 258 microg/m(3)) and 54 (49 ng/m(3) vs 09 ng/m(3)), respectively As for indoor levels, the winter/summer ratios were 14 (332 microg/m(3) vs 244 microg/m(3)) for PM(25) and 54 (43 ng/m(3) vs 08 ng/m(3)) for B[a]P, and for outdoor concentrations, the respective values were 15 (403 microg/m(3) vs 264 microg/m(3), and 68 (61 ng/m(3) vs 09 ng/m(3)) A stronger correlation was found between personal PM(25) exposure and the pollutant concentration indoors (r = 089; 95% CI: 083-093) than outdoors (r = 075; 95% CI: 064-083) The correlations between personal B[a]P exposure and its indoor or outdoor levels were similar (095-096) and significant The markedly higher exposure to B[a]P in Krakow in winter than in summer can be explained by the massive use of coal for heating in the cold season Conclusion We conclude that although ambient PM(25) measurements provide an adequate indicator of outdoor air quality for use in epidemiologic studies, they may not be adequate for studies on relationship between non-ambient pollution and health effects Since only about 20% of variability in personal B[a]P exposure could be explained by personal PM(25) level, the extrapolation of personal exposure to B[a]P from personal PM(25) data may be greatly underestimated

Wheezing and lung function measured in subjects exposed to various levels of fine particles and polycyclic aromatic hydrocarbons

Abstract: The main purpose of the study was to assess the occurrence of wheezing and lung function in non-smoking women exposed to various levels of fine particulate matter(FP) and polycyclic aromatic hydrocarbons (PAH). Out of the total study group, 152 women were included in the lower exposed group (PM2.5 ≤34.3μg/m3 or PAHs ≤ 22.9ng/ m3) and 96 persons in higher concentrations of both air pollutants (PM2.5>34.3μg/m3 and PAHs > 22.9ng/ m3). Except for FVC and FEV1, all lung forced ventilatory flows (PEFR, FEF25% FEF50%, FEF75%, FEF25−75%) were significantly lower in the higher exposed group. The findings suggest bronchoconstriction within the respiratory tract, which may be related to the exposure under study. This was consistent with a higher prevalence of wheezing in more exposed subjects. It was shown that higher levels of both pollutants increased the risk of wheezing by factor 5.6 (95% CI: 1.77–17.8) after accounting for potential confounders such as allergic diseases and exposure to ETS. This study suggests that pollutants in question may have the capacity to promote broncho-constriction and asthmatic symptoms, possibly by bronchial inflammation resulting from the exposure.

Traditional Physical Activity Indexes Derived from the Harvard Alumni Activity Survey Have Low Construct Validity in a Lower Income, Urban Population

Abstract: The purpose of this study is to investigate the construct validity of the Harvard Alumni Activity Survey (HAAS) in an urban, lower income population. Data were collected from 192 smokers enrolled in an antioxidant micronutrient trial. Activity data were compared to body mass index (BMI), diastolic, and systolic blood pressure. The traditional physical activity index (PAI), using data on stair climbing, walking, and sports, was calculated including and excluding body mass. A new scale, the total weekly activity (TWA) scale, was derived from other questions on the HAAS. The PAI scale calculated with body mass was unassociated with BMI and blood pressure. The PAI scale calculated without body mass was unassociated with BMI and systolic blood pressure but was associated with diastolic blood pressure (Beta = −0.001, p = 0.03). The TWA scale was associated with BMI (Beta = −0.01, p = 0.01), diastolic (Beta = −0.03, p = 0.01), and systolic blood pressure (Beta = −0.04, p = 0.01). A one standard deviation change in the TWA scale is predicted to be equivalent to a change of 0.99 BMI units, 2.97 mmHg of diastolic blood pressure, and 3.96 mmHg of systolic blood pressure. This work suggests that the TWA scale has greater construct validity than the traditional PAI scale in this population.

Fluorescence in situ hybridization is necessary to detect an association between chromosome aberrations and polycyclic aromatic hydrocarbon exposure in utero and reveals nonrandom chromosome involvement.

Abstract: Chromosome aberrations are associated with environmental exposures in infants and children. Recently we reported that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) was significantly (P < 0.01) associated with stable aberration frequencies in cord blood from a subset of 60 newborns from the Columbia Center for Children's Environmental Health Prospective Cohort Study (Bocskay K et al. [ 2005]: Cancer Epidemiol Biomarkers Prev 14:506–511). To determine whether the environmental exposures may be targeting specific chromosomes and to compare various methods for measuring chromosome aberrations, we further evaluated this same subset of subjects composed of African-American and Dominican nonsmoking mother–newborn pairs residing in low-income neighborhoods of New York City, and exposed to varying levels of airborne PAHs. Chromosome aberrations were measured in cord blood lymphocytes, both by whole chromosome probe (WCP) fluorescence in situ hybridization (FISH) and traditional Giemsa-staining. Prenatal exposures were assessed by personal air monitoring. Breaks in chromosomes 1–6, as detected by WCP FISH, were nonrandomly distributed, underscoring the importance of appropriate chromosome probe selection to capture cytogenetic damage in response to exposure. FISH for stable aberrations was found to be a more sensitive method for detecting aberration frequencies associated with environmental exposures, when compared with FISH for unstable aberrations or Giemsa-staining for aberrations. Together, these results suggest that PAHs may be targeting specific chromosomes and highlight the importance of using the more sensitive detection methods to assess risk in populations with low levels of exposure. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc.

Risk of wheezing associated with house-dust mite allergens and indoor air quality among three-year-old children. Kraków inner city study.

Abstract: Objectives: The aim of the study was to describe the distribution of house-dust mite (HDM) allergens in homes of three- year-old children and to test the hypothesis whether the content of HDM allergens exceeding 2 μg/g of dust may be regarded as a risk level possibly affecting respiratory health in early childhood. Materials and Methods: House-dust samples were collected in 275 dwellings from mattresses, children's bedrooms and kitchen fl oors. In the laboratory, dust samples were analyzed for Der f 1 and Der p 1 using monoclonal antibody enzyme-linked immunosorbent assays (ELISA). At the time of the house-dust collection, mothers were interviewed on the household characteristics and their children's respiratory health. Respiratory outcome variables included wheezing or whistling in the chest irrespective of respiratory infections. The number of the wheezing episodes and their duration in days over the last 6 months were recorded in the questionnaire. In the multivariate Poisson regression analysis on the association between the occurrence of wheezing and exposure, a set of potential confounders, such as child's gender, maternal education, maternal allergy, older siblings, presence of moulds, house dampness, and environmental tobacco smoke (ETS) was taken into account. Results: The adjusted incidence rate ratios (IRR) of wheezing ascribed to a higher HDM level (> 2.0 μg/g dust) were 1.84 (95% CI: 1.45-2.34) for duration of wheezing and 1.56 (95% CI: 0.88-2.75) for episodes. Of the confounders taken into consideration, the presence of moulds had the strongest impact on the risk of wheezing (IRR = 4.24; 95% CI: 3.08-5.84). Conclusion: The data support the view that exposure to a higher level of HDM allergens increases the burden of respiratory diseases in the early childhood and the effect is independent of maternal atopy, ETS, and moulds in homes.

Increased burden of respiratory disease in the first six months of life due to prenatal environmental tobacco smoke: Krakow birth cohort study

Abstract: The main purpose of our study was to assess the effects of prenatal tobacco smoke on respiratory symptoms and on doctor consultations in a birth cohort of 445 infants who had no smoking mothers and who had no postnatal exposure to environmental tobacco smoke (ETS). Before and after delivery, questionnaires and interviews with mothers were administered to solicit information on prenatal and postnatal ETS exposure. Newborns were followed‐up over six months of life, and respiratory outcomes such as runny or stuffed nose, cough with or without cold, difficult (puffed) breathing, wheezing or whistling in the chest irrespective of respiratory infection were considered. In addition, medical visits related to the occurrence of respiratory symptoms were recorded for each child over a six‐month study period. In the multivariate Poisson regression analysis, a set of potential confounders has been taken into account such as gender of child, season of birth, gestational age, maternal education, maternal atopy, presenc...

A bibliometric analysis of scientific production in cancer molecular epidemiology. Commentary

Abstract: Objectives: The main purpose of this research was to compare the scientific production in the field of cancer molecular epidemiology among countries and to evaluate the publication trend between 1995 and 2004. Methods: A bibliometric study was carried out searching the PubMed database with a combined search strategy based on the keywords listed in the medical subject headings and a free text search. Only articles from a representative subset of 92 journals-accounting for 80% of papers identified-were selected for the analysis, and the resulting 13 240 abstracts were manually checked according to a list of basic inclusion criteria. The study evaluated the number of publications and the impact factor (mean and sum), absolute and normalized by country population and gross domestic product. Results: A total of 3842 citations were finally selected for the analysis. Thirty-seven percent came from the European Union (UK, Germany, Italy, France and Sweden ranking at the top), 31.6% from USA and 9.7% from Japan. The highest mean impact factor was reported for Canada (6.3), USA (5.9), Finland (5.8) and UK (5.2). Finland, Sweden and Israel had the best ratio between scientific production and available resources. 'Genetic polymorphism, glutathione transferase, breast neoplasm, risk factors, case-control studies and polymerase chain reaction' were the most used keywords in each of the subgroups evaluated, although inclusion criteria may have privileged studies dealing with exogenous carcinogens. Conclusion: Cancer molecular epidemiology is an expanding area attracting an increasing interest. The identification of an operative definition is a necessary condition to give to this discipline a unique scientific identity.