Pahor M, Furberg C D
Department of Preventive Medicine, University of Tennessee, Memphis, USA.
Drugs Aging. 1998 Aug;13(2):99-108. doi: 10.2165/00002512-199813020-00002.
In animal and in vitro studies, several calcium antagonists have been shown to block apoptosis (programmed cell death), a natural cellular defence against cancer. On the basis of these studies, it has been hypothesised that calcium antagonists may function as cancer promoters and that they might cause cancer in humans. The association between the use of calcium antagonists and cancer has been addressed recently in 6 independent epidemiological studies. Four of these studies--2 cohort and 2 case-control--found a significantly higher risk of cancer among users of certain calcium antagonists as compared with either non-users or with users of other antihypertensive agents. The other 2 studies failed to find support for this association. All studies had limitations of varying types and significance. The emerging pattern from these investigations includes the following features: (i) the strength of the association appears to be dependent on daily dosage, ranging from no association in users of low dosages to a 2-fold (or possibly higher) increased risk in users of higher dosages; (ii) the time lag to the appearance of this association appears to be at least 2 to 3 years; (iii) an association with a higher risk of cancer has been found primarily for verapamil, while no such relationship has been reported for diltiazem; and (iv) no highly consistent associations have been shown with specific cancer sites or histological types. More data, preferably from long-term randomised clinical trials, are required before firm conclusions can be drawn.
在动物和体外研究中，已证实几种钙拮抗剂可阻断细胞凋亡（程序性细胞死亡），这是细胞对抗癌症的一种天然防御机制。基于这些研究，有人提出假设，钙拮抗剂可能起到癌症促进剂的作用，并且可能会导致人类患癌。最近有6项独立的流行病学研究探讨了使用钙拮抗剂与癌症之间的关联。其中4项研究——2项队列研究和2项病例对照研究——发现，与未使用者或其他抗高血压药物使用者相比，某些钙拮抗剂使用者患癌风险显著更高。另外2项研究未发现这种关联的证据。所有研究都存在不同类型和程度的局限性。这些调查呈现出的新情况包括以下特点：（i）关联强度似乎取决于每日剂量，低剂量使用者无关联，高剂量使用者患癌风险增加2倍（或可能更高）；（ii）出现这种关联的时间滞后似乎至少为2至3年；（iii）主要发现维拉帕米与患癌风险增加有关，而未报告地尔硫䓬有此类关系；（iv）未显示与特定癌症部位或组织学类型有高度一致的关联。在得出确凿结论之前，需要更多数据，最好是来自长期随机临床试验的数据。
