Micronutrient Malnutrition and EBV Persistence in Children

描述(申请人提供)：地方性Burkitt淋巴瘤是赤道非洲低洼潮湿地区最常见的儿童癌症。在肯尼亚，这种癌症在Nyanza省流行。在Nyanza省，我们已经确定了BL的高风险和低风险聚集性。已经确定了两个已知的BL的共同因素：全地方性疟疾和EBV感染。全地方性疟疾传播在Nyanza省全境发生，EBV感染不受地理限制。这表明，除了EBV和全流行疟疾之外，其他辅助因素增加了BL的风险，导致了BL的高危聚集性。一些证据表明，另一个潜在的辅助因素是微量营养素缺乏症，如硒。缺硒与几种类型的癌症有关，而补硒是降低癌症风险的化学预防措施。我们假设，与低发区相比，缺硒发生在低发区和高发区，因此可能是增加低发区风险的一个额外的辅助因素。此外，我们假设缺硒会导致EBV病毒载量增加。在这项提案中，我们将通过完成以下目标来检验这些假设：确定生活在BL低风险和高风险地区的儿童的硒水平，并确定低硒水平是否与儿童EBV病毒载量增加相关。我们将对生活在Nyanza省两个白血病高风险地区和两个低白血病风险地区的儿童进行横断面分析。这项建议建立在我们在肯尼亚正在进行的研究项目和两名合作调查人员之间的长期合作基础上，一名在纽约州立大学北部，另一名在肯尼亚医学研究所(KEMRI)。作为拟议调查的结果，我们期望在一组易患白血病的儿童中，确定硒缺乏与两个已知的辅助因素，EBV和疟疾之间的相关性。这一知识对于确定BL的病因并最终预防BL至关重要。这项研究将主要在肯尼亚基苏木的肯尼亚医学研究所病媒生物学研究和控制中心与P.Odada Sumba合作进行，作为NIH#R01CA102667号赠款的延伸。公共卫生相关性：Burkitt淋巴瘤仍然是赤道非洲最常见的儿童恶性肿瘤。我们正在研究是什么导致了这种癌症，以及为什么它在儿童中如此常见。我们正在验证这样一种假设，即生活在肯尼亚伯基特淋巴瘤高风险地区的儿童缺乏必要的微量营养素。

DESCRIPTION (provided by applicant): Endemic Burkitt's lymphoma (BL) is the most common childhood cancer in low-lying humid regions of Equatorial Africa. In Kenya, the cancer is endemic in Nyanza Province. Within Nyanza Province, we have identified high risk and low risk clusters of BL. Two known co-factors for BL have been identified: holoendemic malaria and EBV infection. Holoendemic malaria transmission occurs throughout Nyanza Province and infection with EBV is not geographically restricted. This suggests that other co-factors in addition to EBV and holoendemic malaria increase the risk for BL resulting in the high-risk clusters of BL. Several lines of evidence suggest that another potential cofactor is micronutrient deficiency such as selenium. Selenium deficiency is associated with several types of cancer and selenium supplementation is chemopreventative for reducing cancer risks. We hypothesize that selenium deficiency occurs in the high BL risk area compared to the low BL risk area and thus could be an additional co-factor increasing the risk for BL. Furthermore, we hypothesize that selenium deficiency results in increased EBV viral load. In this proposal we will test these hypotheses by completing the following aims: determine selenium levels in children living in regions with low and high risk for BL and determine if reduced selenium levels correlate with elevated EBV viral load in children. We will perform a cross-sectional analysis of children living within two high-BL risk regions and two low-BL risk regions we identified in Nyanza Province. This proposal builds on our ongoing research projects in Kenya and the long- standing collaboration between the two co-investigators, one at SUNY Upstate and one at the Kenya Medical Research Institute (KEMRI). As an outcome of the proposed investigations, we expect to determine how selenium deficiencies correlate with 2 known co-factors, EBV and malaria, in a cohort of children at risk for developing BL. This knowledge is critical to determining the etiology of BL and ultimately, to prevent BL. This research will be done primarily in Kisumu, Kenya at the Center for Vector Biology Research and Control, Kenya Medical Research Institute in collaboration with P. Odada Sumba, as an extension of NIH grant #R01CA102667. Public Health Relevance: Burkitt's lymphoma remains the most common childhood malignancy in Equatorial Africa. We are studying what causes this cancer and why it is so common in children. We are testing the hypothesis that essential micronutrients are deficient in children that are living in a region in Kenya where there is a high risk for getting Burkitt's lymphoma.