- Journal Details
- Format
- Journal
- eISSN
- 2544-4646
- First Published
- 04 Mar 1952
- Publication timeframe
- 4 times per year
- Languages
- English
There has been tremendous progress in science and medicine in recent years, but despite this, cancer is the second leading cause of death after cardiovascular disease and is undeniably one of the most critical public health challenges. Neoplastic cells are characterized by reduced growth control, invasiveness to the tissues in which they occur, and the ability to spread. More and more often, attention is paid to the contribution to neoplasms formation by broadly understood infectious agents (Fol and Jachowicz 2016; Masrour-Roudsari and Ebrahimpour 2017; Palrasu et al. 2021). It is estimated that they could cause up to 20% of cancers. Infectious agents can promote tumor development by affecting cell growth, destabilizing the host's immune system, or leading to changes in cells resulting from long-term infection. The neoplastic process can be a consequence of infections caused by certain viruses (most often), bacteria, or even parasites (Fol and Jachowicz 2016). According to the World Health Organization, in 2020, about 10 million people were diagnosed with new cases of cancer, and stomach cancer was in the sixth place (1.09 million), while in terms of the number of deaths, it was in the fourth place (769 thousand), after lung, colon, and liver cancer (WHO 2021). Stomach cancer incidences and mortality vary greatly depending on environmental factors such as diet, alcohol consumption, smoking, cancer stage at diagnosis, and genetic burden.
The Epstein-Barr virus (EBV) is ubiquitous globally, affecting over 90% of people, and is associated with certain cancers such as post-transplant lymphoproliferative diseases, nasopharyngeal cancer, Hodgkin's lymphoma, and gastric cancer (Shinozaki-Ushiku et al. 2015; Smatti et al. 2018). According to the molecular classification of gastric cancer, Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype in terms of oncogenesis and molecular features and accounts for approximately 10% of cases (Cancer Genome Atlas Research Network 2014; Shinozaki-Ushiku et al. 2015; Yang et al. 2020). EBV has long been linked to some undifferentiated gastric carcinoma, thus indicating that focal EBV infection occurs before oncogenic transformation (Shibata et al. 1991). Interestingly, EBV-positive carcinomas have a better prognosis and a lower percentage of lymph node metastases than EBV-negative carcinomas, as demonstrated by clinical-pathological studies (Kobayashi et al. 2019).
More and more attention is paid to research on the coexistence of
The research performed by Santacroce et al. (2000) has indicated a significant relationship between
The aim of the research was to determine the prevalence of
The admission criterion for the research study was the diagnosis of gastric cancer in an adult patient with no history of other neoplasms. After complete gastrectomy, blood serum was obtained from 32 patients diagnosed with gastric cancer (adenocarcinoma). Patients were treated in 2018–2020 at the 2nd Oncological Surgery Ward – Oncologic Surgery Clinic, Provincial Multispeciality Center of Oncology and Traumatology named after M. Kopernik in Lodz and the Central Clinical Hospital of the Medical University of Lodz. The patient group consisted of 20 men and 15 women, aged 36–93 years (mean age 68). The study was approved by the Bioethics Committee at the Medical University of Lodz (No. RNN/206/19/KE). The reference material was serum obtained from people without neoplastic diseases.
In patients with adenocarcinoma, after complete gastrectomy, the primary tumor size and its’ invasion into adjacent tissues (T), the state of regional lymph nodes (N), and the presence or absence of distant metastases (M) were analyzed histopathologically (TNM classification) (Rosen and Sapra 2021).
Detection of anti-cagA antibodies against
Statistical analysis was performed using Statistica StatSoft Inc. The significance of differences between the control and study groups was assessed using the Kruskal-Wallis test, with the significance level
The results of histopathological analysis are collected in Table I.
The number of tumor specimens (n) classified according to TNM classification and AJCC staging.
| TNM classification | |||||||||
| T1 | T2 | T3 | N0 | T4 | N1 | N3 | N2 | M0 | |
| n | 7 | 3 | 18 | 4 | 11 | 5 | 7 | 9 | 32 |
| AJCC staging | |||||||||
| stage I (localized cancer) | stage II (locally advanced cancer, early stages) | stage III (locally advanced cancer, late stages) | |||||||
| n | 8 | 9 | 15 | ||||||
In search for
Statistical analysis showed a positive correlation (Spearman rank correlation,
Fig. 1
The correlation between tumor stage and the presence of IgG against
Fig. 2
The correlation between tumor size (TNM classification) and the presence of IgG against
Serological analysis of anti-EBV antibodies included IgM and IgG antibodies to capsid antigens (CA), early antigens (EA), and nuclear antigens (EBNA). The avidity of IgG antibodies was also assayed. A positive anti-CA (IgM) results are the classic marker of fresh infection. IgG anti-CA antibodies remain at the same level throughout life. About 6–8 weeks after the infection, antibodies against nuclear antigens (anti-EBNA) are produced, and their presence indicates a past EBV infection. It is helpful to test the avidity, i.e., the binding strength of specific IgG antibodies to the antigen. Thanks to the avidity test, it can be determined whether the positive reaction of IgG antibodies results from a recent or past infection. At first, the immune system responds to infection by producing antibodies in the IgG class with low antigen-binding power (low avidity). As the infection progresses, the avidity of IgG antibodies increases. The late-stage or past infection is suspected if high avidity antibodies are detected. The study on the avidity of anti-CA antibodies in the IgG class in the diagnostics of EBV infections allows for interpretation of the problematic and questionable results. Based on the simultaneous detection of the presence of several specific antibodies, and the assessment of their avidity, it can be estimated whether the antibodies present in the patient's serum are the result of an active infection or the evidence of a past infection. None of the patients had IgM anti-CA antibodies, which would indicate a new infection, but all had high avidity anti-CA IgG antibodies, eight patients had anti-EA IgG antibodies, and five patients did not have anti-EBNA antibodies.
Gastric cancer is one of the most common neoplasms, and since the symptoms of the disease appear at an advanced stage, it is diagnosed very late. It develops due to genetic and environmental factors, such as eating habits, alcohol drinking, cigarette smoking, and excessive body weight. Stomach cancer usually has a poor long-term prognosis; only the five-year survival rate in Japan is relatively good, reaching 90%. In Europe, this value ranges from 10% to 30%. Therefore, it is very essential to understand the etiology and the ability to early diagnose of gastric cancer (Sitarz et al. 2018; Machlowska et al. 2020). Stomach cancer rates increase with age and reach a plateau between 55 and 80. On average, gastric cancer incidence rates are 2 to 3 times higher in men than in women (Machlowska et al. 2020; Thrift and El-Serag 2020). Also, in our study group, the majority of patients were men (20 men versus 12 women), and the age of the patients in most cases ranged from 60 to 80 years.
More and more often, infectious agents are mentioned to trigger cancer development. In the case of gastric cancer,
To the best of our knowledge, this is the first project about the coexistence of
In Poland, little research has been conducted on the epidemiology of
Relatively recently, attention was paid to the role of EBV as an etiological factor in the development of gastric cancer. The presence of viral DNA in cancer cells was confirmed by molecular methods in 1990. It has even been suggested that focal EBV infection occurs before oncogenic transformation (Shibata et al. 1991).
The incidence of EBV infection in gastric cancer ranges from 2 to 20%, the global average is about 10% (Shinozaki-Ushiku et al. 2015). Researches carried out in various regions of the world has shown that the incidence of gastric cancer associated with EBV is different, and in Europe, it is 13.9%, in America – 12.5%, and in Asia – 7.5% (Camargo et al. 2014). The differentiation in the occurrence of EBVaGC can also be observed, depending on individual countries, e.g., it ranges from 4% in China to 17.9% in Germany, while in Poland, it is about 12.5% (Czopek et al. 2003; Sitarz et al. 2018). In our study, based on serological results, the presence of EBV antibodies in the serum of all gastric cancer patients was demonstrated.
Inflammation of the gastric mucosa is much more severe in
Studies on the coexistence of EBV and
In a study conducted by de Souza et al. (2018), the co-infections with
Gastric cancer is one of the most common cancers globally, with a very high mortality rate. Due to the lack of characteristic symptoms, it is usually diagnosed late. Therefore, early and effective diagnosis is critical, and the search for non-invasive markers will allow for early cancer detection and effective treatment. In this respect, it is crucial to understand tumor biology, i.e., the mechanisms underlying the neoplastic process. Although many factors contribute to the development of cancer, both genetic and environmental, the increasingly important role is assigned to infectious factors, primarily
The seroprevalence of
The number of patients included in the study is not large. The material was collected from 2018 to 2020. At the time of the announcement of the SARS-CoV2 pandemic, the access to treatment of diseases other than COVID-19 was limited. Hence, the difficulties in obtaining biological material from cancer patients. That is why we describe the study as a pilot study – to share the results obtained so far. We are still collecting material from patients and will continue our research, extending it to other factors related to gastric carcinogenesis.
Fig. 1
Fig. 2
The number of tumor specimens (n) classified according to TNM classification and AJCC staging.
| TNM classification | |||||||||
| T1 | T2 | T3 | N0 | T4 | N1 | N3 | N2 | M0 | |
| n | 7 | 3 | 18 | 4 | 11 | 5 | 7 | 9 | 32 |
| AJCC staging | |||||||||
| stage I (localized cancer) | stage II (locally advanced cancer, early stages) | stage III (locally advanced cancer, late stages) | |||||||
| n | 8 | 9 | 15 | ||||||
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