Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

<p>Abstract</p> <p>Background</p> <p>Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring.</p> <p>Methods</p> <p>From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion.</p> <p>Results</p> <p>The adjusted ORs and 95% confidence intervals (CI) were 1.69 (0.98, 2.92) during the preconception period; 1.98 (1.13, 3.45) during the index pregnancy; 2.11 (1.17, 3.78) during breastfeeding period; 2.17 (1.28, 3.66) after birth; and 2.06 (1.24, 3.42) for global exposure.</p> <p>Conclusion</p> <p>This is the first study in which an OEI was used to assess a father's occupational exposure to carcinogenic agents as a risk factor for the development of childhood AL in his offspring. From our results, we conclude that children whose fathers have been exposed to a high level of carcinogenic agents seem to have a greater risk of developing acute leukemia. However, confounding factors cannot be disregarded due to an incomplete control for confounding.</p

Occupational exposure to ultraviolet radiation: The duality dilemma

Human exposure to ultraviolet (UV) radiation is a component of everyday life and a significant hazard for outdoor workers. In addition, a large range of artificial sources also has the potential to provide extreme occupational UV exposure. Even though the human health risks of overexposure to UV are well documented, to date relatively little is known quantitatively about UV exposure. For example, the evidence indicates that workers who are exposed to particular sources (for example, welding arcs) are exposed to extreme UV exposures, despite the use of current control measures. In contrast, increasing evidence points to significant health impacts resulting from underexposure to UV, particularly with the production (or more correctly lack of production) of vitamin D in the skin. The latter poses a serious issue for the work-force, with specific risks for workers lacking adequate sun exposure-underground miners, long-haul flight crews, shift workers, and perhaps indoor workers. Using a risk-management approach, this paper provides a comprehensive review of occupational UV sources, health impact of occupational UV exposure, occupational exposure standards, and levels of exposure in various settings, and discusses the appropriate control measures. In addition, the duality aspect of health impacts from overexposure and underexposure to UV and the associated occupational health implications are specifically explored

Disruption of human plasma cell differentiation by an environmental polycyclic aromatic hydrocarbon: a mechanistic immunotoxicological study

Background: The AhR is a ligand-activated transcription factor that mediates immunosuppression induced by environmental PAH and HAH. Recently, a critical role for the AhR in development of T cells involved in autoimmunity (Th17 and Treg) has been demonstrated, supporting the hypothesis that the AhR plays a key role in immune regulation both in the presence and absence of environmental ligands. Despite these results with T cells systems, little is known of the role that the AhR plays in B cell development. We have demonstrated that B cell activation with CD40 ligand, a stimulus that models adaptive immunity, induces AhR expression in primary human B cells, suggesting that activation may increase human B cell sensitivity to AhR ligands and that the AhR may play a role in B cell development. Methods To test these possibilities, we developed an in vitro system in which activated human B cells expressing high AhR levels are induced to differentiate into plasma cells. Consequently, the effects of benzo [a]pyrene, a prototypic environmental AhR ligand, on plasma cell differentiation could be investigated and this chemical could be exploited essentially as drug probe to implicate the role of the AhR in plasma cell development. Results A previously unattainable level of B cell differentiation into plasma cells (up to 45% conversion) was observed. Benzo [a]pyrene significantly suppressed that differentiation. γ-Irradiation after an initial proliferation phase induced by CD40 ligand and immediately prior to initiation of the differentiation phase blocked cell growth but did not affect cell viability or plasma cell differentiation. B [a]P suppressed differentiation whether or not cell growth was inhibited by γ-irradiation. Conclusions 1) Extensive proliferation is not required during the differentiation phase per se for CD40L-activated human B cells to undergo plasma cell differentiation, and 2) an environmental PAH blocks both proliferation and differentiation of AhR expressing B cells. The results uncover a new mechanism by which environmentally ubiquitous PAHs may negatively impact human B cell-mediated immunity.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofNon UBCReviewedFacult