Genetic variation in DNArepair and the risk for lymphoma

DNA修复的遗传变异与淋巴瘤的风险

• 批准号: 6770161
• 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/6770161
• 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）： 在过去的四十年中，在西方世界已经观察到了非霍奇金淋巴瘤（NHL）的发病率趋势上升。尽管如此，所有NHL案件中绝大多数的根本原因，因此，对于日益增加的趋势，仍然是不建立的。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增加，反之亦然。众所周知，许多人群的平均UVR暴露和皮肤癌发病率也会增加。 DNA修复基因型与修复UVR受损的DNA和皮肤癌敏感性的能力有关。我们建议研究与NHL的易感性有关，参与UVR受损的DNA的基因中的多态性是否与易感性有关。我们打算使用在基于NIH的大型种群病例对照研究中收集的血液样本，包括在瑞典和丹麦的总共3,000例NHL病例和2 800个对照中。具体而言，我们计划分析主要参与核苷酸切除修复途径的基因中的21个单核苷酸多态性和单倍型，在500例和500例对照中随机选择的子集中与NHL有关。在病例对照研究中，还收集了有关UVR暴露的问卷数据；因此，拟议的研究还将为我们提供独特的机会，以研究基因 - 环境相互作用分析中相同个体中紫外线暴露的遗传和环境方面。据我们所知，与NHL相关之前，尚未研究与DNA损伤修复有关的遗传方差，例如由UVR诱导。与DNA修复能力相关的多态性可能是个体发展NHL敏感性的重要标志物，也可以作为致癌暴露效应的修饰的标志，例如UVR。鉴于一方面淋巴瘤与皮肤癌之间的有趣关联，另一方面，UVR暴露，DNA修复基因型和皮肤癌之间存在着有趣的关联，我们认为测试这一新假设可能会为NHL病因的谜团增加重要的生物学信息。

项目成果

Lack of association between the MDM2 promoter polymorphism SNP309 and clinical outcome in chronic lymphocytic leukemia.

• DOI: 10.1016/j.leukres.2009.06.006
• 发表时间: 2010-03
• 期刊: Leukemia research
• 影响因子: 2.7
• 作者: M. Kaderi;M. Mansouri;N. Zainuddin;N. Cahill;Rebeqa Gunnarsson;M. Jansson;E. Kimby;A. Åleskog;J. Lundin;B. Glimelius;M. Melbye;G. Juliusson;J. Jurlander;R. Rosenquist