Determinants of gastric and esophageal cancers incidence in the north of Portugal

Summary:

Gastric cancer incidence and mortality have been decreasing for several decades (1), but still is one of the most frequent cancers worldwide. This decline is attributable to a set of factors related to the improvement of the populations’ living conditions, namely the decrease in the frequency of Helicobacter pylori infection, the increase in fruit and vegetables consumption and the decrease in salt intake. More recently, the decrease in the prevalence of tobacco smoking observed in several countries may have also contributed to a lower gastric cancer incidence. The sustained decline over several decades and the apparent potential for an even greater decrease in the disease burden trough specific interventions to control salt intake or smoking as well as the primary prevention of H. pylori infection or its eradication contribute to the misperception that gastric cancer is no longer a public health problem in the more developed countries.
The decline in gastric cancer incidence was mainly attributed to the decrease in the ‘intestinal’ histological type, which predominatesover the ‘diffuse’, that presents stable rates over time and has a poorer prognosis (2). Therefore, the pattern of change that has been observed will expectedly lead to an increase in the relative weight of the ‘diffuse’ tumors, not necessarily resulting in a decrease of the global burden of disease as high as could be anticipated if these subgroup-specific trends are not acknowledged. Similarly, the decline has been greater for tumors located in the lower thirds of the stomach, while tumors in the cardia region, also with poorer prognosis, have been increasing over time, depicting a pattern of change that resembles more closely the observed for esophageal cancer (3).
Esophageal cancer has one of the most letal (survival rates are two- to three-fold lower than for gastric cancer (4)), and the incidence and mortality rates for esophageal cancer have been increasing, namely due to the increase in esophageal adenocarcinoma in western countries as a result of the increased prevalence of its major risk factors’ obesity and gastroesophageal reflux. H. pylori infection is negatively associated with esophageal adenocarcinoma (5) and the reduction in the prevalence of infection is also expected to contribute to a higher number of cases (6).Esophageal cancer is much less frequent in more developed countries than gastric cancer (7) but, despite these differences, there are some common aspects in their etiologies. On the one hand, they are influenced by smoking and fruit and vegetables consumption in asimilar way, and the secular variation of these exposures contributes to changes in the frequency of these tumors that go in the same direction. On the other hand, the changes in the frequency of H. pylori infection are expected to translate into a higher esophageal cancer morbidity and mortality, together with a lower burden of gastric cancer.
Despite the robustness of our current knowledge on the causes of these tumors, it has not been shown how the main determinants operate together to drive the trends in the burden of disease associated with gastric and esophageal cancer. This project intends to build models that explain the variation of gastric and esophageal cancer incidence, and use them to make projections of the disease burden, taking into account the expected variation in the exposure to the main risk factors, and thepotential for the decrease in H. pylori infection to have a double effect, contributing to the decline of gastric cancer and simultaneous increase in the esophageal cancer frequency.
We will quantify how much of the variation in gastric and esophageal cancers incidence between 1995 and 2009 can be attributed to their main determinants, using the north region of Portugal as our study setting. After validating the model using data from other European populations, we will make projections of the burden of disease in 2025 and 2040, taking into account multiple scenarios of change in the exposure to risk factors, namely the potential impact of interventions to prevent and control H. pylori infection, obesity, smoking, alcohol consumption and salt intake.
The expected results of this investigation may be an important scientific breakthrough, by validating at macro level the extensive but sparse knowledge that has been produced on the causes of these cancers, and depicting the true potential for intervention over the known risk factors. The development of a model based in the state of the art of the potential impact of the main cancer determinants, under different assumptions, will allow estimating the medium and long term burden of disease associated with gastric and esophageal cancer, with a direct practical application in the planning of activities of cancer prevention and control.