Forman D
Centre for Cancer Research, University of Leeds, Cookridge Hospital, UK.
Scand J Gastroenterol Suppl. 1996;215:48-51.
The International Agency for Research on Cancer, sponsored by the World Health Organization, has recently categorized Helicobacter pylori infection as a class I carcinogen, based on evidence that this infection increases the risk of gastric cancer. The classification was intentionally qualitative in nature and not associated with any public health recommendations. In addition, no specific causal mechanism was proposed to explain the relationship between H. pylori and gastric cancer. In this paper, the magnitude of the risk, implications of the relationship for the prevention of gastric cancer and nature of the causal mechanisms are considered. Relative risk of gastric cancer may be substantial; even with conservative assumptions, the proportion of new cases of gastric cancer worldwide attributable to H. pylori infection is approximately one third of a million annually. This figure is likely to increase with changes in the age structure of the population, and the eradication of H. pylori as a means of prevention of gastric cancer should be considered. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer, but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, a number of constitutive properties of H. pylori may be of relevance to cancer without being specifically carcinogenic. Thus ammonia, which is produced in abundance as a result of urease activity, may promote cell division. Other relevant properties result from the immune response of the host to the bacterium. For example, the excessive production of reactive oxygen metabolites can lead to extensive DNA damage and molecular mutations.
由世界卫生组织赞助的国际癌症研究机构最近将幽门螺杆菌感染归类为I类致癌物，基于该感染会增加胃癌风险的证据。该分类本质上是定性的，与任何公共卫生建议无关。此外，未提出具体的因果机制来解释幽门螺杆菌与胃癌之间的关系。在本文中，我们考虑了风险的程度、这种关系对预防胃癌的影响以及因果机制的性质。胃癌的相对风险可能很大；即使采用保守假设，全球每年归因于幽门螺杆菌感染的胃癌新病例比例约为百万分之三。随着人口年龄结构的变化，这一数字可能会增加，因此应考虑将根除幽门螺杆菌作为预防胃癌的一种手段。对中年人群进行筛查并治疗感染者的策略实施起来可能相对便宜，但疗效完全未知，需要在随机对照试验中进行评估。如果将胃癌作为终点，旨在解决普通人群中这一问题的研究需要大规模且长期进行。关于致癌机制，幽门螺杆菌的许多固有特性可能与癌症相关，但并非具有特异性致癌性。因此，由于脲酶活性而大量产生的氨可能促进细胞分裂。其他相关特性源于宿主对该细菌的免疫反应。例如，活性氧代谢产物的过度产生会导致广泛的DNA损伤和分子突变。
