Association of inflammatory genes and prostate cancer

描述（由申请人提供）：前列腺癌具有重要的公共卫生重要性，因为它是美国男性中最常见的癌症和癌症死亡的第二大原因。虽然前列腺癌的病因尚不清楚，但流行病学研究一致表明这种疾病的遗传易感性。迄今为止，鉴定易感基因的努力主要集中在与雄激素生物合成和生长因子有关的基因上。然而，仍有几种候选途径尚未得到充分研究。众所周知，慢性或复发性炎症在许多人类癌症的发展中起着致病作用。前列腺组织中的炎症变化已经被发现多年，这导致人们猜测炎症可能有助于前列腺癌的发展。炎症在肿瘤发生和发展中的确切机制仍有待阐明，可能很复杂。炎症相关的DNA损伤、细胞凋亡减少（绕过p53）、生长和生存因子、血管生成、侵袭和转移都可能在前列腺癌的发生和发展中发挥作用。我们假设一些炎症基因的序列变异与前列腺癌风险相关。为了验证这一假设，我们建议：1)在瑞典收集的已建立的前列腺癌病例对照人群中，对前列腺癌风险与炎症基因序列变异的相关性进行探索性测试；2)在第二个新收集的瑞典前列腺癌病例对照人群中，对前列腺癌风险与炎性基因序列变异亚群的关联进行确证性测试；3)探索htsnp和htsnp单倍型对两种研究人群中炎性基因亚群在血清和/或前列腺组织中相应蛋白水平的功能影响。这些问题的答案将大大提高我们对前列腺癌炎症作用的认识，并将指导我们识别其他前列腺癌基因的努力。

DESCRIPTION (provided by applicant): Prostate cancer is of significant public health importance because it is the most common cancer and the second leading cause of cancer death among men in the United States. Although the etiology of prostate cancer remains unknown, epidemiologic studies have consistently demonstrated genetic susceptibility to this disease. To date, efforts to identify susceptibility genes have primarily focused on genes involved in androgen biosynthesis and growth factors. However, there remain several candidate pathways that have yet to be adequately studied. Chronic or recurrent inflammation is known to play a causative role in the development of many human cancers. Inflammatory changes have been recognized in prostate tissues for many years, leading to speculation that inflammation might contribute to prostate cancer development. The exact mechanism by which inflammation might act in tumor development and progression remains to be elucidated and is likely to be complex. Inflammation-associated DNA damage, decreased apoptosis (bypassing p53), growth and survival factors, angiogenesis, invasion and metastasis may all play a role in the development and progression of prostate cancer. We hypothesize that sequence variants in a number of inflammatory genes are associated with prostate cancer risk. To test this hypothesis, we propose to 1) perform exploratory tests for association of Prostate cancer risk with inflammatory gene sequence variants in an established Prostate cancer case-control population that was collected in Sweden, 2) perform confirmatory tests for association of Prostate cancer risk with a subset of inflammatory gene sequence variants that have been implicated in the first population in a second newly collected Swedish Prostate cancer case-control population and 3) explore the functional impact of htSNPs and htSNP-haplotypes on the corresponding protein levels in serum and/or prostate tissue for a subset of inflammatory genes that have been implicated in both study populations. Answers to these questions will significantly improve our knowledge of the role of inflammation in prostate cancer and will guide our efforts in identifying additional prostate cancer genes.