Asian Pacic Journal of Cancer Prevention, Vol 12, 2011
Chronic Hepatitis B Virus Infection and Pancreatic Cancer in Southern China
Newly diagnosed without treatment
Newly diagnosed with treatment
Persistence or recurrence
Caldwell S, Park SH (2009). e epidemiology of hepatocellular
cancer: from the perspectives of public health problem to
tumor biology. J Gastroenterol, 44 Suppl 19, 96-101.
Coussens LM, Werb Z (2002). Inammation and cancer. Nature,
de Gonzalez AB, Jee SH, EA E (2009). No association between
hepatitis B and pancreatic cancer in a prospective study in
Korea. J Clin Oncol, 27, 648-9.
Dejean A, Lugassy C, Zafrani S, et al (1984). Detection of hepatitis
B virus DNA in pancreas, kidney and skin of two human
carriers of the virus. J Gen Virol, 65 ( Pt 3), 651-5.
El-Serag HB, Engels EA, Landgren O, et al (2009). Risk of
hepatobiliary and pancreatic cancers after hepatitis C
virus infection: A population-based study of U.S. veterans.
Hepatology, 49, 116-23.
Everhart J, Wright D (1995). Diabetes mellitus as a risk factor
for pancreatic cancer. A meta-analysis. JAMA, 273, 1605-9.
Ganem D, Prince AM (2004). Hepatitis B virus infection--
natural history and clinical consequences. N Engl J Med,
Gordon SC, Gish RG (2009). Hepatitis B not a player in
Pancreatic Cancer. American Association for the Study of
Liver Diseases (AASLD) 60th Annual Meeting Poster 1486,
Presented November 2, 2009.
Hassan MM, Li D, El-Deeb AS, et al (2008). Association between
hepatitis B virus and pancreatic cancer. J Clin Oncol, 26,
Hidalgo M (2010). Pancreatic cancer. N Engl J Med, 362, 1605-17.
Hoefs JC, Renner IG, Askhcavai M, et al (1980). Hepatitis
B surface antigen in pancreatic and biliary secretions.
Gastroenterology, 79, 191-4.
Hohenberger P (1985) e pancreas as target organ for hepatitis B
virus--immunohistological detection of HBsAg in pancreatic
carcinoma and chronic pancreatitis. Leber Magen Darm,
Hong SG KJ, Lee YS, Yoon E, et al (2010). e relationship
between hepatitis B virus infection and the incidence of
pancreatic cancer: a retrospective case-control study. Korean
J Hepatol, 16, 49-56.
Iloeje UH, Yang HI, Jen CL, et al (2010). Risk of pancreatic
cancer in chronic hepatitis B virus infection: data from the
REVEAL-HBV cohort study. Liver Int, 30, 339-41.
Jemal A, Siegel R, Ward E, et al (2008). Cancer statistics. CA
Cancer J Clin, 58, 71-96.
Katakura Y, Yotsuyanagi H, Hashizume K, et al (2005). Pancreatic
involvement in chronic viral hepatitis. World J Gastroenterol,
Lee WM (1997). Hepatitis B virus infection. N Engl J Med, 337,
Oksuzoglu B, Kilickap S, Yalcin S (2002). Reactivation of hepatitis
B virus infection in pancreatic cancer: a case report. Jpn J
Clin Oncol, 32, 543-5.
Pawlotsky JM, Lonjon I, Hezode C, et al (1998). What strategy
should be used for diagnosis of hepatitis C virus infection in
clinical laboratories? Hepatology, 27, 1700-2.
Shepard CW, Simard EP, Finelli L, et al (2006). Hepatitis B virus
infection: epidemiology and vaccination. Epidemiol Rev,
Sherman M (2010). Pancreatic cancer in chronic hepatitis B.
Liver Int, 30, 339-41.
Wang F, Xu RH, Han B, et al (2007). High incidence of hepatitis
B virus infection in B-cell subtype non-Hodgkin lymphoma
compared with other cancers. Cancer, 109, 1360-4.
HBV epidemic countries such as China and Korea have a
relatively lower incidence of pancreatic cancer. erefore,
the result of our study is reasonable from this perspective.
Interestingly, we found the prevalence of HBeAg was
signicantly higher in pancreatic cancer patients, (2.6%
vs. 0.9%, P=0.03). Further analysis indicated that HBeAg
was a risk factor for pancreatic cancers (OR=2.935, 95%
CI: 1.048-8.220). HBeAg is a marker of HBV replication,
and the seroconversion from HBeAg to anti-HBe is
considered as a sign of disease recovery. Some studies
have demonstrated that continuous HBeAg detection
increases the risk of hepatocellular carcinoma (Yang
et al., 2002; Yang et al, 2010). e possible association
between HBeAg and pancreatic cancer may lie in similar
mechanism: high-titer HBV replication stimulates
continuous inammatory response, which could be a
pivotal step of tumor progression (Coussens and Werb,
2002). Nevertheless, the study was not designed for
HBeAg and the patients who are seropositive of HBeAg
is quite few in both groups of our study especially in the
control group, so it is not proper to make conclusions.
Moreover, there might be another explanation that HBV
reactivation was secondary to oncogenesis considering
frequent suppression of immunity function in cancer
patient (Oksuzoglu et al., 2002). We also found that the
prevalences of anti-HBs, anti-HBe and anti-HBc were
even higher in the control group. e reason may lie in
suppression of immunity function, either (Oksuzoglu et
al., 2002). We will do further research to make it clear.
In this study, we also found that diabetes mellitus was
associated with pancreatic cancer signicantly with the
OR of 1.462(95% CI: 1.029-2.077) which coincided with
the reported risk association between pancreatic cancer
and diabetes mellitus (Everhart and Wright, 1995). In
addition, there have been reports of high frequency of
HCV infection in pancreatic patients (Hassan et al.,
2008; El-Serag et al., 2009). Similarly, we found that the
prevalence of anti-HCV and Anti-HEV was higher in
pancreatic cancer patients than that in control group.
However, logistic regression didn’t identify them as risk
factors, and we will increase the sample size to conrm
the conclusion in further study.
Our study has some limitations. As a case-control
study, the control group came from other patients but
not the healthy individuals, allowing the possibility of
admission bias. However, the prevalence of HBV in our
study was similar with previous report in the same area
(Wang et al., 2007), suggesting that control group is
qualied to represent the general population of the area.
Furthermore, all patients were from HBV endemic district,
with the infection prevalence much higher than other
district of China, so the result can’t represent the situation
of the whole country. is problem will be solved in the
upcoming prospective study.
In summary, current evidence indicated that there was
no signicant association between chronic HBV infection
and pancreatic cancer. However, the data provided some
hints that HBeAg may play a role in the development of
pancreatic cancer. is study is the rst one to report the
relationship between HBV infection and pancreatic cancer
in Mainland China and further studies are expected to
conrm our conclusion.