CELAC and European consortium for a personalized medicine approach to Gastric Cancer (LEGACy)

Globally, gastric cancer (GC) is the third leading cause of cancer death in
both sexes worldwide (723,000 deaths, 8.8% of the total)1.Despite multiple
attempts to improve treatment in recent decades, no strategies have improved
prognosis in locally advanced stage III and IVGC. Urgent intervention is
therefore needed. The highest estimated mortality rates are in Eastern Asia (24
per 100,000 in men, 9.8 per 100,000 in women), with the lowest in Northern
America (2.8 and 1.5, respectively). High mortality rates are also present in
both sexes in Central and Eastern Europe, and in Central and South America1.
Histologically, GCs can be divided into two types, diffuse and intestinal.
Epidemiological and molecular features of GCs can vary widely according to
their histological type, location and genetic makeup of the tumour. Tumour
location at a proximal site is more common in Europe and CELAC countries
(approximately 20%) than in Asia-Pacific, where antral location predominates.
Signet-ring cell histology predominates except in Europe, where adenocarcinoma
is most prevalent2.The reasons behind these differences are multiple and
complex and may include genetic susceptibility, strains of the bacterium
Helicobacter pylori (H. pylori) and dietary factors. In particular, H. pylori
infection plays an important role in GC incidence. Similarly, about 10% of GC
patients test positive for infection by the Epstein Barr Virus (EBV)3.
Interestingly, EBV is characteristic of South American populations. Several
other factors, non-related to infectious agents, including excessive
consumption of salty food, the ingestion of poorly preserved, smoked or pickled
foods; contamination of food by aflatoxin, nitrates or fungi; pernicious
anaemia and smoking are also associated with GC4,5,6.
The implementation of better screenings for high-risk populations in Japan, a
country with high incidence of GC, resulted in a dramatic shift in stage at
diagnosis along with a reduction in GC-related mortality7. Conversely, Western
Countries with more restricted access to screening programs have seen a
dramatic increase in GC8,9. Late diagnosis is probably one of the main reasons
for the high mortality rates observed in GCs, in fact at least half of GC
patients are diagnosed at advanced stages of the disease. On the other hand,
most studies and current international databases on late-stage/advanced GC are
largely based on Asian populations; in sharp contrast, the tumour biology and
genome of European Union (EU)or Community of CELAC and Caribbean State
(CELAC)populations remains poorly known. Furthermore, existing database genomic
information is poorly integrated with clinical data from patients, due
principally to a lack of multi-omics profiling, long turn-around times and the
high costs behind bioinformatics analyses. These factors have contributed to
the low number of clinical practice guidelines based on current information.
Prevention is a key factor in medicine, especially in cancer. In recent years,
the arrival of personalized (or precision) medicine has revolutionized
available treatments for cancer patients. Consequently, here we propose a novel
concept: *personalized prevention*. From a public health standpoint, prevention
can be conducted at three levels: primary, secondary, and for improving
outcomes at the advanced stage of disease. Surprisingly, the concept
*personalized medicine* has been restricted to this last setting, which relates
to improving outcomes of already diagnosed patients in order to avoid cancer
progression. However, we speculate that the first two levels of prevention can
also benefit from a *personalized* approach, by identifying high-risk
populations, working on specific measures based on the specific health
situation of each country. To this end, precise risk prediction models need to
be constructed. Epidemiologists aim to integrate *omics* data along with
crucial information coming from other sources (questionnaires, candidate
markers) that has been proved to be relevant in discrimination risk assessment
of complex diseases.

Western Management strategies have been ineffective to modify the poor
prognosis of GC. This proposal will focus on this specific challenge to
*improve GC outcomes*, and will seek to gather evidence through international
high-quality translational collaborative research, to tailor GC control with
coordinated and consensual measures of intervention at different levels of
prevention, each adapted to the different characteristics of the countries
participating in this project: CELAC (Mexico, Chile, Argentina and Paraguay)
and European cohorts (Spain, Netherlands, Portugal, Belgium and Germany).
In the selection of CELAC countries participating in this multicentre
case-control project, we have included countries with a high incidence of GC
such as Chile, and others with medium incidence, such as Mexico, Argentina and
Paraguay. Currently there are no accurate data regarding GC incidence and
characteristics in CELAC countries, so the registries proposed in this project
will be of great value to demonstrate as a pilot how the useful strategies
proposed will improve GC outcomes.

Prospective cohort study.

It is very likely that patients will not see any health benefits from
participating in this study.
Any risks and inconveniences will arise from the gastroscopy. Performing
biopsies can cause slight bleeding. Needle puncture collection is not a problem
for most people. However, sometimes they can cause bleeding, bruising,
discomfort, infections and / or pain at the site of the blood sample. You may
also feel dizzy.
For biopsy purposes during the gastroscopy procedure a different gastroscopy
may be necessary. This will cause minimal physical discomfort for the patient
because the patient is sedated during the procedure.