Hepatitis B virus as a risk factor for gastric cancer

Gastric cancer (GC) is one of the most common malignant diseases in the digestive system, contributing to ∼10% of annual deaths from cancer. Although the incidence of GC has been declined for several decades, it is still the fourth most common cancer in men and fifth in women. Several risk factors have been explored. The most thoroughly investigated and commonly recognised factor is the infection of
Helicobacter pylori (Hp).
 The prevalence of hepatitis B virus (HBV) infection varies largely worldwide. The relatively high prevalence areas are located in some developing countries, including China.
Hepatitis B virus is considered to be a hepatotrophic virus, and it has long been confirmed to be the most important risk factor for hepatocellular carcinoma. However, several studies have probed the existence of HBV in some extrahepatic organs and tissues, such as the kidneys, skin, lymph nodes, bone marrow, vessel walls, colon, pancreas as well as stomach.

In a study by Chen et al (2004 ), the coexistence of Hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) with Hp immunoglobulin G antigen in gastric antrum mucosa was observed in patients with chronic HBV infection or HBV-related cirrhosis. In addition, they found that there was no difference in the rates of HBV antigen expression between the Hp- positive and -negative patients. It was also found that patients with liver cirrhosis had a high prevalence of gastric ulcers and an increased risk of GC. Besides, the impact of Hp on gastric ulcers in patients with liver cirrhosis was found to be relatively weak. It is well known that HBV infection is the most important risk factor for liver cirrhosis in China. We therefore speculate that HBV infection may play a role in the risk of GC in China, as China is an endemic region for both GC and HBV infection. However, the markers of either past or present HBV infection could possibly be also frequently detectable in patients with GC. The relation between HBV infection and GC might be a casual association.
HBV infection has been confirmed to be a risk factor for several cancers of other organs and tissues involved in HBV infection. Hepatocellular carcinoma is well known as one of the HBV-related cancers. As HBV infection also exists in gastric mucosa epithelial cells, it may be possible that HBV infection increases the risk of GC in a similar mechanism of HBV-related hepatocellular carcinoma. The HBV infection has been commonly recognised as a risk factor for hepatocellular carcinoma.

The mechanism of HBV-induced hepatocellular carcinoma has been thoroughly researched, and it is complex, including direct enhancement of chromosomal instability by integration of HBV DNA into the host genome that results in alterations of host gene expression and signalling pathways. Indirect mechanisms, such as persistent inflammation, oxidative stress, hypoxia caused by cirrhosis and sequential angiogenesis, are also raised up. Recently, the epigenetic changes generated by the HBV-encoded X (HBx) protein became another focus in the exploration for mechanism of HBV-induced hepatocellular carcinoma. However, to understand the authentic and detailed mechanism of HBV infection-related GC, more studies should be conducted.

Journal References

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