Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
Pharmacoepidemiol Drug Saf. 2019 Apr;28(4):471-478. doi: 10.1002/pds.4702. Epub 2018 Dec 19.
Increased expression of Vacuolar-type H ATPases (V-ATPases), in the plasma membrane of cancer cells has been suggested to contribute to the development of aggressive cancer phenotypes by promoting acidic tumor microenvironments. Accumulating data suggest that proton pump inhibitors (PPIs) may elicit a chemopreventive effect via V-ATPase inhibition in some cancers, but evidence is still limited. Therefore, we aimed to explore a potential preventive role of PPIs in this study.
In this population-based case-control study, we identified incident cases of breast cancer (n = 1739), prostate cancer (n = 1897), and malignant melanoma (n = 385) in Iceland between 2005 and 2014 from the Icelandic Cancer Registry. We assessed varying levels of PPI use through record linkages to the Icelandic Medicines Registry. For each case, we selected up to 10 age-matched, sex-matched, and calendar-matched population controls using risk-set sampling. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) controlling for NSAID use.
Adjusted ORs associated with ever use of PPIs were 1.03 (95% CI: 0.92-1.16) for breast cancer, 1.12 (95% CI: 1.00-1.25) for prostate cancer, and 0.84 (95% CI: 0.69-1.12) for malignant melanoma. Analyses of high use of PPIs (≥1000 DDDs) yielded ORs of 0.97 (95% CI: 0.78-1.19), 1.20 (0.99-1.47), and 0.59 (0.40-1.13) for breast cancer, prostate cancer, and malignant melanoma, respectively. Analyses of cumulative exposure to PPIs did not support a dose-response relationship for any of the three cancer types.
Our findings do not support a chemopreventive effect of PPI use on breast cancer, prostate cancer, or malignant melanoma.
研究表明，癌细胞质膜中 V-ATPase（液泡型 H+ATP 酶）表达增加，通过促进酸性肿瘤微环境，有助于形成侵袭性癌症表型。越来越多的证据表明，质子泵抑制剂（PPIs）通过抑制 V-ATPase 在某些癌症中可能具有化学预防作用，但证据仍然有限。因此，本研究旨在探讨 PPI 的潜在预防作用。
本研究采用基于人群的病例对照设计，于 2005 年至 2014 年期间，从冰岛癌症登记处确定了 1739 例乳腺癌、1897 例前列腺癌和 385 例恶性黑色素瘤的发病病例，并通过与冰岛药品登记处的记录链接来评估不同水平的 PPI 使用情况。针对每个病例，我们采用风险集抽样法选择了最多 10 名年龄、性别和日历相匹配的人群对照。采用条件逻辑回归，在控制非甾体抗炎药使用的情况下，计算比值比（OR）和 95%置信区间（CI）。
调整 NSAID 使用情况后，PPIs 总使用与乳腺癌（OR=1.03，95%CI：0.92-1.16）、前列腺癌（OR=1.12，95%CI：1.00-1.25）和恶性黑色素瘤（OR=0.84，95%CI：0.69-1.12）的相关性均无统计学意义。高剂量 PPI（≥1000 DDDs）使用与乳腺癌（OR=0.97，95%CI：0.78-1.19）、前列腺癌（OR=1.20，95%CI：0.99-1.47）和恶性黑色素瘤（OR=0.59，95%CI：0.40-1.13）的相关性也均无统计学意义。对 PPI 累积暴露量的分析结果也不支持这三种癌症的任何一种存在剂量-反应关系。
本研究结果不支持 PPI 使用对乳腺癌、前列腺癌或恶性黑色素瘤具有化学预防作用。
