Nordic Gastric and Esophageal Tumor Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 900,000
- 试验地点
- 1
- 主要终点
- Gastric adenocarcinoma
研究概览
简要总结
This is a population-based case-control study in all 5 Nordic countries from 1994 onwards. Cases with esophageal or gastric cancer will be compared with 10 times as many population controls.
The project includes a specific study "Long-term medication with proton pump inhibitors and risk of gastric cancer", which is summarized here:
Research question: Medication with proton pump inhibitors (PPI) is a most commonly used drug, prompted by its good anti-acidic efficacy and short-term safety profile. Gastric cancer is the 3rd leading cause of cancer-related mortality globally, responsible for 770,000 deaths each year. There are biological mechanisms linking long-term PPI-use with an increased risk of gastric cancer. But existing research has not provided a definite answer to whether long-term PPI-use increases risk of gastric cancer. The literature is hampered by short follow-up time, insufficient statistical power, lack of population-based design and confounding.
With the availability of nationwide complete drug registries in the Nordic countries, the first two starting in 1994 (Denmark and Finland), we can now, by adding registry data from all Nordic countries, conduct the first study providing a robust and valid answer to this research question.
Overarching aim To clarify if (and if so to what extent) long-term PPI-therapy increases the risk of gastric adenocarcinoma.
For validation reasons, we will also examine how long-term use of histamine-2-receptor blockers (H2RB) influences the risk of developing gastric adenocarcinoma. These analyses will validate that the findings are specific for PPIs. H2RB are used for the same indications as PPIs, but with a different biological mechanism.
Hypothesis Long-term use of PPI (but not H2RB) increases the risk of gastric adenocarcinoma.
Prerequisites
This will be the first project with all prerequisites to provide conclusive answers to the hypotheses above, i.e.:
- Long follow-up (up to 28 years)
- Complete follow-up (by virtue of the nationwide complete Nordic registries)
- Population-based design (which rules out biased selection of cases or controls)
- Sufficient statistical power (all five Nordic countries participate with nationwide data)
- High-quality data on exposures, outcomes and confounders (thanks to well-maintained and complete nationwide Nordic health data registries)
- Control for confounding factors (available for all participants, both cases and controls)
详细描述
PROJECT DESCRIPTION
Theory and method
Study design We will conduct a nationwide and population-based multi-national case-control study in the five Nordic countries during the total study period from 1994 through 2022, thus allowing up to 28 years of follow-up. The start of the study period will vary between countries depending on when their national drug registries started, i.e. in 1994 (Denmark), 1994 (Finland), 2002 (Iceland), 2004 (Norway) and 2005 (Sweden).
Participants The study will include all adult residents in Sweden, Denmark, Finland, Iceland and Norway with a first gastric adenocarcinoma diagnosed during the study period according to the national cancer registries. The control participants are selected from the general populations of the five countries and frequency-matched for age, sex, calendar year, and country. The index date for matching is the date of gastric adenocarcinoma diagnosis. For each case of gastric cancer, 10 control participants will be included. Because the controls are matched within each country by age and calendar year, the time-window used to ascertain the exposure will be the same in cases and controls. We will have the same detailed information on all study variables in cases and controls.
Exposure The exposure is long-term PPI-use. Two definitions will be used. The first, high PPI-consumption, is defined as >180 defined daily doses (DDD) of PPI per year during the time from start of the drug registry or entry in the cohort until the index date. The second definition is cumulative exposure to PPI, defined by the total number of DDDs consumption during the time window of exposure. The DDDs are retrieved from the prescribed drug registries. From a Swedish cohort of 8,276,316 adult individuals of the general population that we use for research purposes, 496,579 (6.0%) were exposed to long-term PPI-use (>180 DDDs).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of esophageal or gastric tumor or frequency matched population control participants
排除标准
- •Age below 18 years
结局指标
主要结局
Gastric adenocarcinoma
时间窗: 5 years
Risk of developing gastric adenocarcinoma using logistic regression providing odds ratios
次要结局
- Esophageal cancer(5 years)
研究者
Jesper Lagergren
Professor of Surgery
Karolinska Institutet