Recent Submissions

  • Clara cells protein, prolactin and transcription factors of protein NF-ĸB and c-Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble form.

    Hałatek, Tadeusz; Stanisławska, Magdalena; Świercz, Radosław; Domeradzka-Gajda, Katarzyna; Kuraś, Renata; Wąsowicz, Wojciech; Nofer Institute of Occupational Medicine (2018-10-23)
    Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m<sup>3</sup> of respirable-size welding dust (mean diameter 1.17 μm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase - LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613-632.
  • Noise exposure and hearing status among call center operators.

    Pawlaczyk-Luszczynska, Malgorzata; Dudarewicz, Adam; Zamojska-Daniszewska, Małgorzata; Zaborowski, Kamil; Rutkowska-Kaczmarek, Paulina; Nofer Institute of Occupational Medicine
    The overall objective of the study was to assess noise exposure and audiometric hearing threshold levels (HTLs) in call center operators. Standard pure-tone audiometry and extended high-frequency audiometry were performed in 78 participants, aged 19 to 44 years (mean ± standard deviation: 28.1 ± 6.3 years), employed up to 12 years (2.7 ± 2.9 years) at one call center. All participants were also inquired about their communication headset usage habits, hearing-related symptoms, and risk factors for noise-induced hearing loss (NIHL). Noise exposure under headsets was evaluated using the microphone in a real ear technique as specified by ISO 11904-1:2002. The background noise prevailing in offices was also measured according to ISO 9612:2009. A personal daily noise exposure level calculated by combining headset and nonheadset work activities ranged from 68 to 79 dBA (74.7 ± 2.5 dBA). Majority (92.3%) of study participants had normal hearing in both ears (mean HTL in the frequency range of 0.25-8 kHz ≤20 dB HL). However, their HTLs in the frequency range of 0.25 to 8 kHz were worse than the expected median values for equivalent highly screened otologically normal population, whereas above 8 kHz were comparable (9-11.2 kHz) or better (12.5 kHz). High-frequency hearing loss (mean HTLs at 3, 4, and 6 kHz >20 dB HL) and speech-frequency hearing loss (mean HTLs at 0.5, 1, 2, and 4 kHz >20 dB HL) were noted in 8.3% and 6.4% of ears, respectively. High-frequency notches were found in 15.4% of analyzed audiograms. Moreover, some of call center operators reported hearing-related symptoms. Further studies are needed before firm conclusions concerning the risk of NIHL in this professional group can be drawn.
  • [Non-occupational but work-related diseases - Legislation, judicature and potential implications to employers and employees in Poland].

    Marcinkiewicz, Andrzej; Tomczak, Paulina; Wiszniewska, Marta; Walusiak-Skorupa, Jolanta; Dorre-Kolasa, Dominika; Nofer Institute of Occupational Medicine (2018-10-30)
    Non-occupational work-related diseases refer to health problems of multifactorial etiology, the occurrence, development and prognosis of which may be affected by work environment or by the way the work is performed but are not treated as occupational diseases under the applicable law. When analyzing their impact on labor market, it is necessary to also consider the employees' right to put in a claim for compensation due to the consequences of the occurrence of such diseases. Legal regulations as well as judicial decisions on the possibilities and methods of pursuing claims for compensation from an employer due to the occurrence of non-occupational work-related disease were analyzed. The analyzed legal regulations and judicial decisions referred to the regulations of the Labour Code, Civil Code and Resolution of the Supreme Court of 4 December 1987. The paper presents examples of non-occupational diseases considered to be work-related and conditions necessary to assert a claim by the employee at the court. Despite the lack of precise legal regulations in Poland, non-occupational work-related diseases may impact the legal situation of employees as well as employers. Employees are granted the right to claim for compensation from their employers in accordance with the Civil Code. Depending on the employer's legal responsibility, it is necessary to prove the meeting of the appropriate essential conditions to put in a claim for damage. Raising the employers' awareness of the legal and financial consequences shall support the occupational medicine services in intensifying their activity aimed at preventing all work-related diseases. Med Pr 2018;69(5):539-546.
  • Sex-Dependent Impact of Low-Level Lead Exposure during Prenatal Period on Child Psychomotor Functions.

    Polanska, Kinga; Hanke, Wojciech; Pawlas, Natalia; Wesolowska, Ewelina; Jankowska, Agnieszka; Jagodic, Marta; Mazej, Darja; Dominowska, Jolanta; Grzesiak, Mariusz; Mirabella, Fiorino; Chiarotti, Flavia; Calamandrei, Gemma; Nofer Institute of Occupational Medicine (2018-10-16)
    The impact of exposure to lead on child neurodevelopment has been well established. However, sex differences in vulnerability are still not fully explained. We aimed at evaluating the effect of a low-level lead exposure, as measured between 20 to 24 weeks of pregnancy and in cord blood, on developmental scores up to 24 months of age in 402 children from the Polish Mother and Child Cohort (REPRO_PL). Additionally, sex-dependent susceptibility to lead at this very early stage of psychomotor development was assessed. The blood lead levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). In order to estimate the children's neurodevelopment, the Bayley Scales of Infant and Toddler Development was applied. The geometric mean (GM) for blood lead level during 20⁻24 weeks of pregnancy was 0.99 ± 0.15 µg/dL and, in the cord blood, it was 0.96 ± 0.16 µg/dL. There was no statistically significant impact of lead exposure during prenatal period on the girls' psychomotor abilities. Among the boys, we observed lower scores for cognitive functions, along with increasing cord blood lead levels (β = -2.07;
  • Sociodemographic determinants for initiation and duration of breastfeeding - Polish Mother and Child Cohort Study

    Kwarta, Paulina; Polanska, Kinga; Jerzyńska, Joanna; Stelmach, Wlodzimierz; Krakowiak, Jan; Karbownik, Michał; Król, Anna; Hanke, Wojciech; Stelmach, Iwona; Nofer Institute of Occupational Medicine (2018-12-05)
  • The diet structure and body mass index among Polish preschool children in relation to their place of residence.

    Potocka, Adrianna; Jacukowicz, Aleksandra; Nofer Institute of Occupational Medicine (2018)
    The present study provides evidence that the nutritional status of children should be analyzed in the context of their place of residence. Thus, the differences between regions and their impact on the health status of their inhabitants should be taken into account when designing preventive or corrective measures.
  • Revision of reciprocal action of mercury and selenium.

    Kuraś, Renata; Janasik, Beata; Wąsowicz, Wojciech; Stanisławska, Magdalena; Nofer Institute of Occupational Medicine (2018-10-23)
    Diverse forms of mercury (Hg) have various effects on animals and humans because of a variety of routes of administration. Inorganic mercury (iHg) binds to thiol groups of proteins and enzymes in one's body or is methylated by microorganisms. Organic form of Hg, contrary to the iHg, is more stable but may be demethylated to Hg2+ in the tissue of intestinal flora. Selenium (Se) also occurs in a variety of chemical forms in one's body but both of these elements behave very differently from one another. Mercury binding to selenide or Se-containing ligands is a primary molecular mechanism that reduces toxicity of Hg. Complexes formed in such a way are irreversible, and thus, biologically inactive. Se deficiency in a human body may impair normal synthesis of selenoproteins and its expression because expression of mRNA may be potentially regulated by the Se status. This paper provides a comprehensive review concerning Hg-Se reciprocal action as a potential mechanism of protective action of Se against Hg toxicity as well as a potential detoxification mechanism. Although interactions between Hg-Se have been presented in numerous studies concerning animals and humans, we have focused mainly on animal models so as to understand molecular mechanisms responsible for antagonism better. The review also investigates what conclusions have been drawn by researchers with respect to the chemical species of Se and Hg (and their relationship) in biological systems as well as genetic variations and expression and/or activity of selenoproteins related to the thioredoxin (thioredoxin Trx/TrxR) system and glutathione metabolism. Int J Occup Med Environ Health 2018;31(5):575-592.
  • The effect of prenatal exposure on disposition of hexachloronaphthalene in female Wistar rats and fetal compartment.

    Stragierowicz, Joanna; Sitarek, Krystyna; Grobelski, Bartłomiej; Kilanowicz, Anna; Nofer Institute of Occupational Medicine (2018-10-24)
    This paper is the first to detail the concentrations of HxCN in the maternal tissues and the transplacental transfer of the tested compound to the fetuses. The exposure of pregnant rats to HxCN results in its accumulation in the maternal liver, fat tissue, reproductive and nervous system, and particularly in the fetal brain. This demonstrates both the effective absorption and significant systemic accumulation which could lead to negative health implications. Int J Occup Med Environ Health 2018;31(5):685-695.
  • The effect of repeated cadmium oral exposure on the level of sex hormones, estrous cyclicity, and endometrium morphometry in female rats.

    Nasiadek, Marzenna; Danilewicz, Marian; Sitarek, Krystyna; Świątkowska, Ewa; Daragó, Adam; Stragierowicz, Joanna; Kilanowicz, Anna; Nofer Institute of Occupational Medicine (2018-10)
    Cadmium (Cd) is regarded as a potential endocrine disruptor. However, the exact mechanism by which this metal may interfere with the reproductive system has not yet been elucidated. The present study aimed to investigate the effect of subacute Cd oral administration at daily doses of 0.09, 1.8, and 4.5 mgCd/kg b.w. and the impact of Cd on sex hormones (estradiol (E2) and progesterone (P)) in the plasma and uterus, as well as on estrous cyclicity and histopathological changes in uterine and ovary in female rats after terminating the exposure and after a prolonged observation period (3 months). Moreover, Cd bioaccumulation in the uterine and brain tissue of rats was analyzed. The study revealed that oral Cd exposure induced changes in the plasma levels of steroid hormones: decrease in E2 and increase in P after the highest dose of Cd. Probably, for the first time, it was evidenced that circulation sex hormone disturbances in Cd-exposed rats caused irregular estrous cycle, persisting for 3 months after exposure termination; no alterations in these hormone levels in uterine tissue were noted. Cd did not induce estradiol-like hyperplasia of endometrium, but resulted in endometrial edema irrespective of the dose, and caused damage of the ovaries after the highest dose. In summary, subacute oral exposure of female rats to Cd may lead to long-term disturbances in reproductive system.
  • Sleep quality and methylation status of selected tumor suppressor genes among nurses and midwives.

    Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata; Nofer Institute of Occupational Medicine (2018)
    Chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited reports suggest also epigenetic effects, such as changes in DNA methylation profiles. The study aims to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of selected tumor suppressor genes. A cross-sectional study was conducted on 710 nurses and midwives aged 40-60 years. Data from interviews regarding sleep habits and potential confounders were used. The methylation status of tumor suppressor genes was determined via qMSP reactions using DNA samples derived from leucocytes. No significant findings were observed in the total study population or in the two subgroups of women stratified by the current system of work. A borderline significance association was observed between a shorter duration of sleep and an increased methylation level in CDKN2A among day working nurses and midwives. Further studies are warranted to explore this under-investigated topic.
  • Response to Noise Emitted by Wind Farms in People Living in Nearby Areas.

    Pawlaczyk-Łuszczyńska, Małgorzata; Zaborowski, Kamil; Dudarewicz, Adam; Zamojska-Daniszewska, Małgorzata; Waszkowska, Małgorzata; Nofer Institute of Occupational Medicine (2018)
    The aim of this study was to evaluate the perception and annoyance of noise from wind turbines in populated areas of Poland. A questionnaire inquiry was carried out among 517 subjects, aged 18⁻88, living within 204⁻1726 m from the nearest wind turbine. For areas where respondents lived, A-weighted sound pressure levels (SPLs) were calculated as the sum of the contributions from the wind power plants in the specific area. It has been shown that the wind turbine noise at the calculated A-weighted SPL of 33⁻50 dB was perceived as annoying or highly annoying by 46% and 28% of respondents, respectively. Moreover, 34% and 18% of them said that they were annoyed or highly annoyed indoors, respectively. The perception of high annoyance was associated with the A-weighted sound pressure level or the distance from the nearest wind turbine, general attitude to wind farms, noise sensitivity and terrain shape (annoyance outdoors) or road-traffic intensity (annoyance indoors). About 48⁻66% of variance in noise annoyance rating might be explained by the aforesaid factors. It was estimated that at the distance of 1000 m the wind turbine noise might be perceived as highly annoying outdoors by 43% and 2% of people with negative and positive attitude towards wind turbines, respectively. There was no significant association between noise level (or distance) and various health and well-being aspects. However, all variables measuring health and well-being aspects, including stress symptoms, were positively associated with annoyance related to wind turbine noise.
  • [The prophylactic operational model integrated with occupational healthcare - Prophylactic of some types of cancers among women].

    Wiszniewska, Marta; Magnuska, Jadwiga; Lipińska-Ojrzanowska, Agnieszka; Pepłońska, Beata; Hanke, Wojciech; Kalinka, Jarosław; Skręt-Magierło, Joanna; Zadrożny, Marek; Walusiak-Skorupa, Jolanta; Nofer Institute of Occupational Medicine (2018-08-20)
    Periodical medical examinations are mandatory for employees in Poland. This rule makes a unique opportunity during occupational health services for implementation of prophylactic activities focused on early diagnosis of various diseases, including cancers. Epidemiological data about cancers is alarming and what is more, further increase in development of cancers is being predicted in population overall. The highest incidence of cancers in the case of Polish women belongs to breast cancer (21.7% of diagnosed cancers in general), while the morbidity rate for uterine cancer, ovarian cancer and cervical cancer amounts to 7.4%, 4.7% and 3.5%, respectively. The aim of this study was to elaborate an algorithm of prophylactic activities integrated with the occupational healthcare system, based on medical literature review and guidelines concerning prophylaxis of selected cancers. Polish cancers' prophylaxis programs related to risk factors were presented in this publication and practical indications for occupational healthcare physicians were worked out. Med Pr 2018;69(4):439-455.
  • [The usefulness of bronchial challenge tests in the diagnosis of occupational asthma].

    Nowakowska-Świrta, Ewa; Wiszniewska, Marta; Walusiak-Skorupa, Jolanta; Nofer Institute of Occupational Medicine (2018-08-20)
    Bronchial hyperresponsiveness (BHR) is the individual ability to respond with bronchoconstriction to a variety of specific and nonspecific stimuli which do not cause these symptoms among healthy subjects. Bronchial hyperresponsiveness is one of the hallmark features of asthma. The degree of bronchial hyperresponsiveness is variable among individuals with asthma and may correlate to its severity (the more severe asthma the higher bronchial hyperreactivity). Bronchial hyperresponsiveness is evaluated by performing bronchial provocation test (BPT). Provocation tests are classified - according to their mechanisms - into direct and indirect tests. Direct challenge tests are highly sensitive and they are used primarily to rule out asthma. In contrast, provocation tests with indirect stimuli are less sensitive but more specific to the direct tests; they are used generally to confirm the diagnosis of asthma and they allow for more accurate conclusions about inflammatory lesions in the case of a patient. Bronchial provocation tests play a significant role in occupational medicine. They are particularly relevant to be performed prior to employment, during periodic examinations, and to diagnose and monitor both occupational asthma and work-related asthma. This article presents selected bronchial provocation tests and their usefulness in the diagnosis of occupational asthma. Med Pr 2018;69(4):457-471.
  • Vitamins A and E during Pregnancy and Allergy Symptoms in an Early Childhood-Lack of Association with Tobacco Smoke Exposure.

    Gromadzinska, Jolanta; Polanska, Kinga; Kozlowska, Lucyna; Mikolajewska, Karolina; Stelmach, Iwona; Jerzyńska, Joanna; Stelmach, Włodzimierz; Grzesiak, Mariusz; Hanke, Wojciech; Wasowicz, Wojciech; Nofer Institute of Occupational Medicine (2018)
    Epidemiological studies have suggested an association between maternal antioxidant levels during pregnancy and development of allergic diseases in their offspring. The aim of the study was to determine plasma vitamins A and E concentration in the 1st trimester of pregnancy, at delivery and in cord blood and to search for a relationship with allergy in up to 2-year-old children who were prenatally exposed or not exposed to tobacco smoke. The study participants included 252 mother-child pairs from Polish Mother and Child Cohort. Vitamin concentrations were measured using the HPLC-UV method, smoking status—as saliva cotinine level using the HPLC-MS/MS technique. Children’s health status was assessed using a questionnaire and pediatricians/allergists examination. Cord plasma vitamin concentrations were significantly lower than their levels in maternal plasma in the 1sttrimester and at delivery (p < 0.001). Significantly higher concentrations of vitamin E have been shown to occur during the 1st trimester of pregnancy in plasma of the women who have actively/passively smoked cigarettes compared to the non-smokers (p < 0.02). Multivariate analysis with inclusion of a variety of confounding factors have not indicated any statistically significant associations between β-carotene, vitamins A and E and the risk of food allergy, atopic dermatitis and wheezing in their children up to 2 years of age. The interaction between smoking during pregnancy and vitamins levels on the risk of allergy was not statistically significant (p < 0.4). The relationship between plasma concentration of vitamins A and E, and the risk of allergy in their young children has not been demonstrated.
  • Urinary Bisphenol A Levels and Male Fertility.

    Radwan, Michał; Wielgomas, Bartosz; Dziewirska, Emila; Radwan, Paweł; Kałużny, Paweł; Klimowska, Anna; Hanke, Wojciech; Jurewicz, Joanna; Nofer Institute of Occupational Medicine (2018-11)
    Bisphenol A (BPA) is a high-production volume industrial chemical found in many consumer products. BPA is a suspected potent endocrine disruptor, with endocrine-disrupting properties demonstrated in animal studies. Few human studies have examined bisphenol A exposure in relation to male fertility and, results are divergent. The aim of the study is to examine the associations between urinary BPA concentration and male fertility. Bisphenol A urinary concentrations were measured using gas chromatography coupled with tandem mass spectrometry in 315 men under 45 years of age with normal sperm concentration (⩾15 mln/ml) recruited from a male reproductive health clinic. Participants were interviewed and provided a semen sample. BPA was detected in 98.10% of urine samples, with a median concentration of 1.87 µg/l (1.63 µg/ g creatinine). A multiple linear regression analysis identified a positive association between the urinary concentrations of bisphenol A 25th-50th percentile and total sperm sex chromosome disomy ( p = .004). Also when modeled as continuous variable urinary BPA concentration increased total sperm sex chromosome disomy ( p = .01). Urinary concentration of BPA also increase the percentage of immature sperm (HDS) ( p = .018) and decrease motility ( p = .03). The study provides evidence that exposure to BPA is associated with poorer semen quality. Future studies are needed to confirm these findings.
  • The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells - genotoxic risk assessement.

    Woźniak, Ewelina; Sicińska, Paulina; Michałowicz, Jaromir; Woźniak, Katarzyna; Reszka, Edyta; Huras, Bogumiła; Zakrzewski, Jerzy; Bukowska, Bożena; Nofer Institute of Occupational Medicine (2018-10)
    Glyphosate is the most heavily applied among pesticides in the world, and thus human exposure to this substance continues to increase. WHO changed classification of glyphosate to probably cancerogenic to humans, thus there is urgent need to assess in detail genotoxic mechanism of its action. We have assessed the effect of glyphosate, its formulation (Roundup 360 PLUS) and its main metabolite (aminomethylphosphonic acid, AMPA) in the concentration range from 1 to 1000 μM on DNA damage in human peripheral blood mononuclear cells (PBMCs). The cells were incubated for 24 h. The compounds studied and formulation induced DNA single and double strand-breaks and caused purines and pyrimidines oxidation. None of compounds examined was capable of creating adducts with DNA, while those substances increased ROS (including •OH) level in PBMCs. Roundup 360 PLUS caused damage to DNA even at 5 μM, while glyphosate and particularly AMPA induced DNA lesions from the concentration of 250 μM and 500 μM, respectively. DNA damage induced by glyphosate and its derivatives increased in order: AMPA, glyphosate, Roundup 360 PLUS. We may conclude that observed changes were not associated with direct interaction of xenobiotics studied with DNA, but the most probably they occurred through ROS-mediated effects.
  • In vitro and in vivo activity of cyclopeptide Dmt-c[d-Lys-Phe-Asp]NH2, a mu opioid receptor agonist biased toward β-arrestin.

    Gach-Janczak, Katarzyna; Piekielna-Ciesielska, Justyna; Adamska-Bartłomiejczyk, Anna; Wtorek, Karol; Ferrari, Federica; Calo', Girolamo; Szymaszkiewicz, Agata; Piasecka-Zelga, Joanna; Janecka, Anna; Nofer Institute of Occupational Medicine (2018-07)
    Morphine and related drugs, which are the most effective analgesics for the relief of severe pain, act through activating opioid receptors. The endogenous ligands of these receptors are opioid peptides which cannot be used as antinociceptive agents due to their low bioactivity and stability in biological fluids. The major goal of opioid research is to understand the mechanism of action of opioid receptor agonists in order to improve therapeutic utility of opioids. Analgesic effects of morphine are mediated mostly through activation of the mu opioid receptor. However, in the search for safer and more effective drug candidates, analogs with mixed opioid receptor profile gained a lot of interest. Recently, the concept of biased agonists able to differentially activate GPCR downstream pathways, became a new approach in the design of novel drug candidates. It is hypothesized that compounds promoting G-protein signaling may produce analgesia while β-arrestin recruitment may be responsible for opioid side effects. In this report we showed that replacement of the tyrosine residue in the mu-selective ligand Tyr-c[d-Lys-Phe-Asp]NH2 with 2',6'-dimethyltyrosine (Dmt) produced a cyclopeptide Dmt-c[d-Lys-Phe-Asp]NH2 with mu/delta opioid receptor agonist profile. This analog showed improved antinociception in the hot-plate test, probably due to the simultaneous activation of mu and delta receptors but also significantly inhibited the gastrointestinal transit. Using the bioluminescence resonance energy transfer (BRET) assay it was shown that this analog was a mu receptor agonist biased toward β-arrestin. β-Arrestin-dependent signaling is most likely responsible for the observed inhibition of gastrointestinal motility exerted by the novel cyclopeptide.
  • Radiation-Induced Lens Opacities among Interventional Cardiologists: Retrospective Assessment of Cumulative Eye Lens Doses.

    Struelens, L; Dabin, J; Carinou, E; Askounis, P; Ciraj-Bjelac, O; Domienik-Andrzejewska, J; Berus, D; Padovani, R; Farah, J; Covens, P; Nofer Institute of Occupational Medicine (2018)
    This study describes the retrospective lens dose calculation methods developed and applied within the European epidemiological study on radiation-induced lens opacities among interventional cardiologists. While one approach focuses on self-reported data regarding working practice in combination with available procedure-specific eye lens dose values, the second approach focuses on the conversion of the individual whole-body dose to eye lens dose. In contrast with usual dose reconstruction methods within an epidemiological study, a protocol is applied resulting in an individual distribution of possible cumulative lens doses for each recruited cardiologist, rather than a single dose estimate. In this way, the uncertainty in the dose estimate (from measurement uncertainty and variability among cardiologists) is represented for each individual. Eye lens dose and whole-body dose measurements have been performed in clinical practice to validate both methods, and it was concluded that both produce acceptable results in the framework of a dose-risk evaluation study. Optimal results were obtained for the dose to the left eye using procedure-specific lens dose data in combination with information collected on working practice. This method has been applied to 421 interventional cardiologists resulting in a median cumulative eye lens dose of 15.1 cSv for the left eye and 11.4 cSv for the right eye. From the individual cumulative eye lens dose distributions obtained for each cardiologist, maxima up to 9-10 Sv were observed, although with low probability. Since whole-body dose values above the lead apron are available for only a small fraction of the cohort and in many cases not for the entire working career, the second method has only been used to benchmark the results from the first approach. This study succeeded in improving the retrospective calculation of cumulative eye lens doses in the framework of radiation-induced risk assessment of lens opacities, but it remains dependent on self-reported information, which is not always reliable for early years. However, the calculation tools developed can also be used to make an assessment of the eye lens dose in current practice.
  • Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

    Ji, Xuemei; Bossé, Yohan; Landi, Maria Teresa; Gui, Jiang; Xiao, Xiangjun; Qian, David; Joubert, Philippe; Lamontagne, Maxime; Li, Yafang; Gorlov, Ivan; de Biasi, Mariella; Han, Younghun; Gorlova, Olga; Hung, Rayjean J.; Wu, Xifeng; McKay, James; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C.; Caporaso, Neil; Johansson, Mattias; Liu, Geoffrey; Bojesen, Stig E.; Le Marchand, Loic; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C.; Bush, William S.; Tardon, Adonina; Rennert, Gad; Chen, Chu; Teare, M. Dawn; Field, John K.; Kiemeney, Lambertus A.; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B.; Andrew, Angeline S.; Shen, Hongbing; Hong, Yun-Chul; Yuan, Jian-Min; Bertazzi, Pier A.; Pesatori, Angela C.; Ye, Yuanqing; Diao, Nancy; Su, Li; Zhang, Ruyang; Brhane, Yonathan; Leighl, Natasha; Johansen, Jakob S.; Mellemgaard, Anders; Saliba, Walid; Haiman, Christopher; Wilkens, Lynne; Fernandez-Somoano, Ana; Fernandez-Tardon, Guillermo; van der Heijden, Erik H. F. M.; Kim, Jin Hee; Dai, Juncheng; Hu, Zhibin; Davies, Michael P. A.; Marcus, Michael W.; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C.; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Doherty, Jennifer; Goodman, Gary E.; Cox, Angela; Taylor, Fiona; Woll, Penella; Brüske, Irene; Manz, Judith; Muley, Thomas; Risch, Angela; Rosenberger, Albert; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances; Tsao, Ming-Sound; Arnold, Susanne M.; Haura, Eric B.; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M.; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J.; Butler, Lesley M.; Koh, Woon-Puay; Gao, Yu-Tang; Houlston, Richard; McLaughlin, John; Stevens, Victoria; Nickle, David C.; Obeidat, Ma’en; Timens, Wim; Zhu, Bin; Song, Lei; Artigas, María Soler; Tobin, Martin D.; Wain, Louise V.; Gu, Fangyi; Byun, Jinyoung; Kamal, Ahsan; Zhu, Dakai; Tyndale, Rachel F.; Wei, Wei-Qi; Chanock, Stephen; Brennan, Paul; Amos, Christopher I.; Nofer Institute of Occupational Medicine (2018-08-13)
    Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
  • Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

    Li, Yafang; Xiao, Xiangjun; Han, Younghun; Gorlova, Olga; Qian, David; Leighl, Natasha; Johansen, Jakob S; Barnett, Matt; Chen, Chu; Goodman, Gary; Cox, Angela; Taylor, Fiona; Woll, Penella; Wichmann, H -Erich; Manz, Judith; Muley, Thomas; Risch, Angela; Rosenberger, Albert; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Houlston, Richard; Soler Artigas, María; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Liu, Geoffrey; Bojesen, Stig E; Wu, Xifeng; Marchand, Loic Le; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C; Bush, William S; Tardon, Adonina; Rennert, Gad; Teare, M Dawn; Field, John K; Kiemeney, Lambertus A; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B; Andrew, Angeline S; Bertazzi, Pier Alberto; Pesatori, Angela C; Christiani, David C; Caporaso, Neil; Johansson, Mattias; McKay, James D; Brennan, Paul; Hung, Rayjean J; Amos, Christopher I; Nofer Institute of Occupational Medicine; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA; Department of Medicine, The Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen University, Herlev, Denmark; Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Public Health Sciences Division, Cancer Prevention Program, Swedish Medical Center, Seattle, WA, USA; Department of Oncology, University of Sheffield, Sheffield UK; Department of Oncology, University of Sheffield, Sheffield UK; Department of Oncology, University of Sheffield, Sheffield UK; Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany; Biobank and Tumor Documentation, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; Biobank and Tumor Documentation, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; Department of Genetic Epidemiology, Medical School, Georg-August University of Göttingen, Göttingen, Germany; Markey Cancer Center, University of Kentucky, Lexington, KY, USA; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Thoracic Surgery Division, “Marius Nasta” National Institute of Pneumology, București, Romania; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; Internal Medicine, School of Medicine, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia; Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center, Institute of Oncology, Warsaw, Pol; Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia; International Organization for Cancer Prevention and Research, Belgrade, Serbia; Department of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, Warsaw, Pol; International Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France; Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Pol; Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Toxicology, National Institute of Occupational Health, Oslo, Norway; Department of Toxicology, National Institute of Occupational Health, Oslo, Norway; Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; The Institute of Cancer Research, London, UK; Department of Health Sciences, Genetic Epidemiology Group, University of Leicester, Leicester, UK; Department of Medical Biosciences, Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden; Medical Oncology Toronto, Princess Margaret Hospital, Toronto, ON, Canada; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK; Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, London, UK; Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark; Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece; Molecular and Nutritional Epidemiology Unit, CSPO (Cancer Research and Prevention Centre), Scientific Institute of Tuscany, Florence, Italy; Princess Margaret Cancer Centre, Toronto, ON M5G, Canada; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA; Department of Genetic Epidemiology, University Medical Center, Georg-August University Göttingen, Göttingen, Germany; Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Medicina, IUOPA-Universidad de Oviedo, Oviedo, Spain; Technion Faculty of Medicine, Clalit National Cancer Control Center, Carmel Medical Center, Haifa, Israel; Genetic Epidemiology, School of Health and Related Research, University of Sheffield, Sheffield, UK; Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department for Health Evidence, Radboud University Medical Center, Nijmegen EZ, Netherlands; Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, USA; Department of Toxicology, National Institute of Occupational Health, Oslo, Norway; Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Epidemiology, Norris Cotton Cancer Center, Dartmouth College, Hanover, NH, USA; Department of Preventive Medicine, IRCCS Foundation Cà Granda Ospedale, Maggiore Policlinico, University of Milan, Milan, Italy; Department of Clinical Sciences and Community Health–DISCCO, University of Milan, Milan, Italy; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA; International Agency for Research on Cancer, World Health Organization, Lyon, France; International Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France; International Agency for Research on Cancer, World Health Organization, Lyon, France; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada; Biomedical Data Science Department, Dartmouth College, Hanover, NH, USA (2018-03)
    Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

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