Genetic variation in DNA repair and risk for lymphoma

DNA 修复的遗传变异与淋巴瘤风险

• 批准号: 6650441
• 负责人: HANS-OLOV ADAMI
• 金额: $ 5.4万
• 依托单位: KAROLINSKA INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650441
• 关键词: DNA repair; Scandinavian country; cancer risk; clinical research; environmental exposure; gene environment interaction; genetic polymorphism; genetic susceptibility; human subject; light adverse effect; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nonHodgkin's lymphoma; skin neoplasms; solar radiation; ultraviolet radiation

DESCRIPTION (provided by applicant): Rising incidence trends of non-Hodgkin's lymphoma (NHL) have been observed in the Western world during more than four decades; still, the underlying causes for the vast majority of all cases of NHL, and consequently, for the increasing temporal trends, remain unestablished. Different lines of evidence indicate an association between ultraviolet radiation (UVR) exposure and risk of NHL, including increased occurrence of lymphomas in skin cancer patients and vice versa. Average levels of UVR exposure and skin cancer incidence are also known to increase in many populations. DNA repair genotypes relate to the capacity to repair UVR-damaged DNA and to skin cancer susceptibility. We propose to investigate if polymorphisms in genes involved in repair of UVR-damaged DNA are associated also with susceptibility for NHL. We intend to use blood samples collected in a large NIH-supported population-based case-control study, including in total 3 000 NHL cases and 2 800 controls in Sweden and Denmark. Specifically, we plan to analyze if 21 single nucleotide polymorphisms and haplotypes in genes involved mainly in the nucleotide excision repair pathway, are associated with NHL in a subset of 500 cases and 500 controls selected at random. In the case-control study, questionnaire data on UVR exposure has also been collected; therefore, the proposed study will, in addition, give us the unique opportunity to investigate both genetic and environmental aspects of UV exposure in the same individuals in analyses of gene-environment interaction. To our knowledge, genetic variance related to repair of DNA damage, induced for example by UVR, has not been investigated before in association with NHL. Polymorphisms associated with DNA repair capacity may be important markers of the individual's susceptibility to develop NHL, and may also serve as markers of modification of a carcinogenic exposure effects, UVR, for example. In light of the intriguing associations between lymphomas and skin cancer on one hand, and between UVR exposure, DNA repair genotype, and skin cancer on the other, we believe that testing this novel hypothesis might add important biological information to the enigma of NHL etiology.

描述（由申请人提供）： 在西方世界，40多年来已经观察到非霍奇金淋巴瘤（NHL）的发病率呈上升趋势;然而，绝大多数NHL病例的根本原因以及因此增加的时间趋势仍未确定。不同的证据表明紫外线辐射（UVR）暴露与NHL风险之间存在关联，包括皮肤癌患者淋巴瘤的发生率增加，反之亦然。紫外线辐射暴露的平均水平和皮肤癌的发病率在许多人群中也有所增加。DNA修复基因型与修复紫外线损伤DNA的能力和皮肤癌易感性有关。我们建议调查是否参与修复紫外线损伤DNA的基因多态性也与NHL的易感性。我们打算使用在NIH支持的大型基于人群的病例对照研究中收集的血液样本，包括瑞典和丹麦的总计3000例NHL病例和2800例对照。具体来说，我们计划分析，如果21个单核苷酸多态性和单倍型的基因主要涉及核苷酸切除修复途径，与NHL在一个子集的500例和500例对照随机选择。在病例对照研究中，还收集了关于紫外线辐射暴露的问卷数据;因此，拟议的研究将为我们提供独特的机会，在基因-环境相互作用分析中，在同一个体中调查紫外线暴露的遗传和环境方面。据我们所知，与DNA损伤修复相关的遗传变异，例如由UVR诱导的，以前没有研究过与NHL相关。与DNA修复能力相关的多态性可能是个体发展NHL的易感性的重要标志，并且也可以作为致癌暴露效应（例如UVR）改变的标志。鉴于淋巴瘤和皮肤癌之间的有趣关联，以及UVR暴露，DNA修复基因型和皮肤癌之间的关联，我们认为，测试这一新的假设可能会为NHL病因之谜增加重要的生物学信息。