文章：

前列腺癌变中的炎症

Inflammation in prostate carcinogenesisk

原文发布日期：2007-04-01

DOI: 10.1038/nrc2090

类型: Review Article

开放获取: 否

要点：

1. Prostate cancer is the most common form of non-skin cancer in men in developed countries. The cause(s) of prostate cancer have not yet been clarified. Although heritable factors are implicated, immigration studies indicate that environmental exposures are also important.
2. Chronic infection and inflammation cause cancer in several organs including the stomach, liver and large intestine. Data from histopathological, molecular histopathological, epidemiological and genetic epidemiological studies show that chronic inflammation might also be important in prostate carcinogenesis.
3. The source of intraprostatic inflammation is often unknown, but might be caused by infection (for example, with sexually transmitted agents), cell injury (owing to exposure to chemical and physical trauma from urine reflux and prostatic calculi formation), hormonal variations and/or exposures, or dietary factors such as charred meats. The resultant epithelial cellular injury might cause a loss of tolerance to normal prostatic antigens, resulting in a self-perpetuating autoimmune reaction.
4. Exposures to infectious agents and dietary carcinogens are postulated to directly injure the prostate epithelium, resulting in the histological lesions known as proliferative inflammatory atrophy (PIA), or proliferative atrophy. These lesions are postulated to be a manifestation of the 'field effect' caused by environmental exposures.
5. Despite a strong genetic component to prostate cancer risk, no highly penetrant hereditary prostate cancer genes have been uncovered to date. Although complex, genetic variation in inflammatory genes is associated with prostate cancer risk.
6. Several challenges remain regarding the inflammation hypothesis in prostate cancer, including the determination of the cause(s) of chronic inflammation in the prostate, an understanding of the cellular and molecular biology of the immune response in the prostate, whether inflammatory cells are truly causative in the process, and the determination of the target cell types within the proposed precursor lesions of prostate cancer.
7. The refinement and application of new epidemiological approaches, including high-throughput genetic epidemiology, improved rodent models of prostate inflammation and cancer, and advances in the application of molecular techniques to histopathological studies should provide insights into the cause of prostate inflammation and its relevance to prostate carcinogenesis.

要点翻译：

1. 前列腺癌是发达国家男性中最常见的非皮肤癌。其病因尚未明确。尽管遗传因素有所牵连，移民研究表明环境暴露同样重要。
2. 慢性感染和炎症可引发多个器官的癌变，包括胃、肝和大肠。来自组织病理学、分子组织病理学、流行病学及遗传流行病学研究的数据表明，慢性炎症在前列腺癌发生过程中可能具有重要作用。
3. 前列腺内炎症的来源通常未知，但可能由感染（如性传播病原体）、细胞损伤（因尿液反流和前列腺结石形成导致的化学与物理创伤）、激素变化和/或暴露、或饮食因素（如烧焦肉类）引起。由此产生的上皮细胞损伤可能导致对正常前列腺抗原的耐受性丧失，从而形成自我延续的自身免疫反应。
4. 据推测，病原体和饮食致癌物的暴露会直接损伤前列腺上皮，形成组织学病变，称为增殖性炎症性萎缩（PIA）或增殖性萎缩。这些病变被认为是环境暴露引起的“场效应”的表现。
5. 尽管前列腺癌风险具有强烈的遗传因素，但至今尚未发现高外显率的遗传性前列腺癌基因。虽然复杂，但炎症基因的遗传变异与前列腺癌风险相关。
6. 关于前列腺癌的炎症假说仍存在若干挑战，包括确定前列腺慢性炎症的病因、理解前列腺免疫反应的细胞和分子生物学机制、明确炎症细胞是否真正参与致病过程，以及在前列腺癌前驱病变中确定靶细胞类型。
7. 新流行病学方法的完善与应用（包括高通量遗传流行病学）、改进的前列腺炎症与癌症啮齿动物模型，以及分子技术组织病理学研究的进展，将为探究前列腺炎症的病因及其与前列腺癌发生的关联提供重要见解。

英文摘要：

About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease.

摘要翻译： 

大约20%的人类癌症由慢性感染或慢性炎症状态引起。近期，针对前列腺癌的发病机制提出了一项新假说。该假说认为，接触环境因素（如感染原和饮食致癌物）以及激素失衡会导致前列腺损伤，并引发慢性炎症及再生性“危险因素”病变，称为增殖性炎症萎缩（PIA）。通过建立新的实验动物模型，并结合经典流行病学研究、遗传流行病学研究及分子病理学方法，我们有望明确前列腺癌是否由炎症驱动，并据此制定新的疾病预防策略。

原文链接：

Inflammation in prostate carcinogenesis