Micronutrient Malnutrition and EBV Persistence in Children

描述（由申请人提供）：地方性伯基特淋巴瘤（BL）是赤道非洲低洼潮湿地区最常见的儿童癌症。在肯尼亚，这种癌症在尼扬扎省流行。在尼扬扎省，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的辅助因素：全地方性疟疾和EBV感染。疟疾全地方性传播在尼扬扎省各地发生，eb病毒感染不受地域限制。这表明，除了eb病毒和全地方性疟疾之外，其他辅助因素也会增加患BL的风险，从而导致BL的高风险聚集。一些证据表明，另一个潜在的辅助因素是微量营养素缺乏，如硒。硒缺乏与几种癌症有关，补充硒是降低癌症风险的化学预防措施。我们假设，与低风险地区相比，硒缺乏发生在BL高风险地区，因此可能是增加BL风险的另一个辅助因素。此外，我们假设硒缺乏导致EBV病毒载量增加。在本提案中，我们将通过完成以下目标来验证这些假设：确定生活在BL低风险和高风险地区的儿童的硒水平，并确定硒水平降低是否与儿童EBV病毒载量升高相关。我们将对我们在尼扬扎省确定的两个bl高危险地区和两个bl低危险地区生活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位共同研究者之间的长期合作基础上，一位在纽约州立大学上州分校，另一位在肯尼亚医学研究所（KEMRI）。作为拟议调查的结果，我们希望确定硒缺乏与两种已知的辅助因素（EBV和疟疾）之间的关系，在一组有发生BL风险的儿童中。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媒介生物学研究和控制中心进行，肯尼亚医学研究所与P. Odada Sumba合作。作为NIH拨款#R01CA102667的延伸。公共卫生相关性：伯基特淋巴瘤仍然是赤道非洲最常见的儿童恶性肿瘤。我们正在研究导致这种癌症的原因，以及为什么它在儿童中如此普遍。我们正在测试一种假设，即生活在肯尼亚某个地区的儿童缺乏必需微量营养素，该地区患伯基特淋巴瘤的风险很高。

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.