Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study.

X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.

Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European study.

Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital-based controls aged 30-79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work-related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76-4.95]. There is evidence for modification of the workplace arsenic-NMSC association by work-related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48-42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC.

Analysis of the effects of exposure to polychlorinated biphenyls and chlorinated pesticides on serum lipid levels in residents of Anniston, Alabama.

BACKGROUND: Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study. METHODS: Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis. RESULTS: We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196-203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components. CONCLUSIONS: Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These observations show selective effects of different organochlorines on serum concentrations of different groups of lipids. This elevation in concentrations of serum lipids may be the basis for the increased incidence of cardiovascular disease found in persons with elevated exposures to PCBs and chlorinated pesticides.

Television and aggression: a test of a mediated model with a sample of Portuguese students.

We examined the role of identification with violent TV heroes, enjoyment of TV violence, and perceived reality in TV violence as mediators of the relationship between viewing TV violence and subsequent physical and verbal aggression. A sample of 722 4th, 6th, and 8th grade students from schools in the central region of Portugal completed measures assessing enjoyment of TV violence, perceived reality, aggression, identification with violent TV heroes, and exposure to TV violence. The results showed that the relationship between TV violence and physical aggression is mediated by enjoyment of TV violence, perceived reality in TV violence, and identification with violent TV heroes. The TV violence to verbal aggression relationship was also mediated by enjoyment of TV violence.

Occupational exposure to PCBs reduces striatal dopamine transporter densities only in women: a beta-CIT imaging study.

We hypothesize that occupational exposure to PCBs is associated with a reduction in central dopamine (DA) similar to changes previously seen in PCB exposed adult non-human primates. To test that hypothesis, we used [(123)I]beta-CIT SPECT imaging to estimate basal ganglia DA transporter density in former capacitor workers. Women, but not men, showed an inverse relationship between lipid-adjusted total serum PCB concentrations and DA transporter densities in the absence of differences in serum PCB concentrations. These sex differences may reflect age-related reductions in the levels of gonadal hormones since these hormones have been shown experimentally to alter response to DA neurotoxicants. These findings may aid in better understanding the roles that sex and age play in modifying central DA function following exposure, not only to PCBs, but also to other DA neurotoxicants as well as further elucidating the role of gonadal hormones in influencing the initiation and/or progression of neurodegenerative disorders.

Evidence of an age-related threshold effect of polychlorinated biphenyls (PCBs) on neuropsychological functioning in a Native American population.

Polychlorinated biphenyls (PCBs) have been suspected for some time of having adverse effects on neuropsychological functioning in humans. While there is evidence of slowing of cognitive function in children associated with exposure to PCBs, the evidence of comparable effects on adults is far less well understood. We report here on the neuropsychological evaluation of 277 Native American adults, ranging in age from 18 to 79, who were exposed to PCBs by way of environmental contamination in the St. Lawrence region of upstate New York. PCB body burden was estimated by 101 PCB congeners and neuropsychological functioning was assessed by a battery of 18 tests. Spline regression models were fitted to the latent variables of memory, motor function, and higher-order executive functioning. After adjusting for age, gender, and education the analyses revealed a threshold effect of PCBs at approximately 2 ppb. An age-by-PCB interaction effect was also observed for several variables which suggests that the threshold effect was largely confined to the age range of 40-79 and was not observable in the 18-40-year-old group. Implications of these results are discussed in comparison to previously published similar work with adults and in terms of its potential clinical meaningfulness.

Practice effects in the prediction of long-term cognitive outcome in three patient samples: a novel prognostic index.

Practice effects, defined as improvements in cognitive test performance due to repeated exposure to the test materials, have traditionally been viewed as sources of error. However, they might provide useful information for predicting cognitive outcome. The current study used three separate patient samples (older adults with mild cognitive impairments, individuals who were HIV+, individuals with Huntington's disease) to examine the relationship between practice effects and cognitive functioning at a later point. Across all three samples, practice effects accounted for as much as 31-83% of the variance in the follow-up cognitive scores, after controlling for baseline cognitive functioning. If these findings can be replicated in other patients with neurodegenerative disorders, clinicians and researchers may be able to develop predictive models to identify the individuals who are most likely to demonstrate continued cognitive decline across time. The ability to utilize practice effects data would add a simple, convenient, and non-invasive marker for monitoring an individual patient's cognitive status. Additionally, this prognostic index could be used to offer interventions to patients who are in the earliest stages of progressive neurodegenerative disorders.

Validation of the Drinking Motives Questionnaire-Revised across US and Portuguese college students.

The present study aimed to evaluate the invariance of the factor structure of the Drinking Motives Questionnaire Revised (DMQ-R) between Portuguese and US university students. Following tests of factor model invariance we further evaluated cross-cultural differences in (1) mean levels of the four motives, and (2) the association of the four motives with weekly drinking, peak drinking, and binge drinking among college students from the United States and Portugal. Participants were 983 undergraduate students (67% female) from the US (N=515) and Portugal (N=468). Participants completed a confidential online (US) or paper and pencil (Portugal) survey. Results of a CFA demonstrated that the four-factor model of the DMQ-R was invariant with respect to factor loadings, factor variances, and factor covariances across the two countries. Mean differences in ratings of drinking motives were found, with US students ranking all motives higher than Portuguese students. However, rank order of motives (social>enhancement>coping>conformity) were equivalent across countries. Support for convergent validity was demonstrated by significant associations between drinking motives and alcohol consumption for men and women of both samples. Results support the factorial invariance and convergent validity of the DMQ-R across US and Portuguese college students, making it a trustworthy means of assessing college students' drinking motives, and a useful instrument for clinical and research purposes, both within and across cultures.

The relationship among neurocognitive performances and biopsychosocial characteristics of elite National Football League draft picks: an exploratory investigation.

Sports neuropsychology has emerged as a specialty area within the field of clinical neuropsychology. The role of the sports neuropsychologist, rooted in baseline and post-concussion testing, has evolved to include other clinical domains, including the clinical assessment of potential draft picks. There is no published information on the neurocognitive characteristics of these draft picks. We sought to determine whether elite NFL draft picks differed from NFL roster athletes on neurocognitive (ImPACT) and biopsychosocial characteristics, and given that no published data exists for this population, adopted null hypotheses. Null hypotheses were rejected for two of the four ImPACT scores, as elite draft picks scored higher on measures of visual motor speed and reaction time than roster NFL athletes. Subtle but distinct neurocognitive differences are noted when comparing elite NFL draft picks with norms from a cumulative roster of a single NFL team.

Occupational exposure to ultraviolet radiation and risk of non-melanoma skin cancer in a multinational European study.

BACKGROUND: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation. OBJECTIVES: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. METHODS: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. RESULTS: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27-0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. CONCLUSIONS: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.

Tibial bone lead, but not serum polychlorinated biphenyl, concentrations are associated with neurocognitive deficits in former capacitor workers.

OBJECTIVE: To determine the relationships between tibial bone lead and serum polychlorinated biphenyl (PCB) concentrations and neurocognitive function. METHODS: The study population consisted of men and women former capacitor workers had been employed by the General Electric Corporation between 1946 and 1977. Regression analyses evaluated the association between neurocognitive function and lipid-adjusted serum PCB and tibia lead concentrations. RESULTS: Tibia lead, but not serum PCBs, was significantly correlated with deficits in neurocognitive function. Women showed more associations between tibia lead and neurocognitive function than men, especially regarding executive function. CONCLUSIONS: These results demonstrate that low levels of tibia lead, but not serum PCBs, are associated with neurocognitive deficits and that postmenopausal women show a greater number of deficits in executive function than men.

Response to acute concussive injury in soccer players: is gender a modifying factor?

OBJECT: Several studies have suggested a gender difference in response to sports-related concussion (SRC). The Concussion in Sport group did not include gender as a modifying factor in SRC, concluding that the evidence at that point was equivocal. In the present study the authors endeavored to assess acute neurocognitive and symptom responses to an SRC in equivalent cohorts of male and female soccer players. The authors hypothesized that female athletes would experience greater levels of acute symptoms and neurocognitive impairment than males. METHODS: Baseline symptom and neurocognitive scores were determined in 40 male and 40 female soccer players by using the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) scale prior to any SRC. After sustaining an SRC, each athlete completed postconcussion ImPACT tests and was carefully matched on a wide array of biopsychosocial variables. Baseline symptom and neurocognitive test scores were compared, and their acute symptoms and neurocognitive responses to concussive injury were assessed. RESULTS: Specific a priori hypotheses about differences between males and females at baseline and at postconcussion measurements of verbal and visual memory ImPACT scores were evaluated according to simple main effects of the gender variable and according to baseline-to-postconcussion main effect and interaction of 2 × 2 split-plot ANOVA. Neither the interaction nor the main effects nor the simple main effects for either ImPACT variable were found to be statistically significant. Exploratory ANOVAs applied to the remaining ImPACT variables of visualmotor speed, reaction time, impulse control, and symptom total scores revealed only a single statistically significant baseline-to-postconcussion main effect for the symptom total. CONCLUSIONS: The results failed to replicate prior findings of gender-specific baseline neurocognitive differences in verbal and visual memory. The findings also indicated no differential gender-based acute response to concussion (symptoms or neurocognitive scores) among high school soccer players. The implications of these findings for the inclusion of gender as a modifying factor in this tightly matched cohort are addressed. Potential explanations for the null findings are discussed.

Estimating the half-lives of PCB congeners in former capacitor workers measured over a 28-year interval.

To date, most estimates of the half-life of polychlorinated biphenyls (PCBs) in humans have been based on relatively short follow-up periods. To address this issue, we determined the half-lives of PCB congeners of occupational origin in the serum of former capacitor workers as part of a study conducted in 2003-2006--approximately 28 years after their last occupational exposure. A total of 241 persons from a source population of 6798 former capacitor workers were interviewed and asked to donate a blood sample for serum PCB congener analysis. A subgroup of 45 participants also had serum archived from 1976 and reanalyzed for the same 27 PCB congeners by the same laboratory. Our estimates of the half-lives of the congeners among these 45 persons were longer than those reported by Wolff et al. (1992), due primarily to the much longer interval between exposure and determination of serum PCB concentrations. Half-lives were significantly greater for the heavy versus light occupational congeners, for women versus men and for those with low versus high initial exposure. Current serum total PCB concentrations, expressed as the geometric mean of wet weight data, averaged 6.7 ng/g for the entire 241-person cohort, which represents a 10-fold decrease from values reported in the late 1970s, but is still nearly twice the average for persons of similar age residing in the same area, but without occupational exposure. In addition, current serum PCB concentrations remained significantly and positively associated with earlier occupational exposure, but were not associated with fresh water fish consumption. In general, the results support a consistent and long-duration trend of increased PCB body burden in this cohort of former capacitor workers compared with non-occupationally exposed individuals. The results may aid in further understanding the toxicological/epidemiological consequences of exposure to PCBs in humans.

Biopsychosocial characteristics and neurocognitive test performance in National Football League players: an initial assessment.

The use of neurocognitive testing in the assessment of professional athletes sustaining sports-related concussions has become widespread over the past decade. Baseline neurocognitive testing is now a requirement for athletes in the National Football League (NFL). We present preliminary normative data on a computer based neurocognitive test (Immediate Post Concussion Assessment and Cognitive Testing; ImPACT) for 159 NFL athletes. Also included are summary data on basic biopsychosocial characteristics, including medical, psychiatric, chemical dependency, concussion, learning disability/attention deficit disorder, and symptom variables, and the relevance of each to baseline neurocognitive test scores.

High serum PCBs are associated with elevation of serum lipids and cardiovascular disease in a Native American population.

We have investigated the relationships among the concentration of total serum polychlorinated biphenyls (PCBs), various PCB congener groupings, and three pesticides to total serum lipids in humans with and without self-reported cardiovascular disease. Blood samples were obtained from 335 adult Akwesasne Mohawks, and were analyzed for 101 PCB congeners, mirex, dichloro-diphenyl-dichloro-ethylene (DDE), and hexachlorobenzene (HCB), as well as serum triglycerides and cholesterol. Structural equation modeling, following the definition of latent variables by means of confirmatory factor analysis, was used to analyze the relationships between serum lipids with PCBs and heart disease. There were significant associations among PCBs, lipids, age, and body mass index (BMI), a fact which justified the application of the structural equation model. Gender of the participant was unrelated to any of the remaining study variables. The results of this study are consistent with a model in which age is considered as both an exogenous explanatory variable and a biological driving mechanism for the acquisition of PCBs. Moreover, the results of this study are consistent with the conclusion that PCBs, acting through P450 enzymes, are directly responsible for increased synthesis of cholesterol and triglycerides, substances known to be major risk factors for cardiovascular disease.