Cell Biochem Biophys DOI 10.1007/s12013-014-0211-2
ORIGINAL PAPER
Preliminary Study of Pancreatic Cancer Associated with Helicobacter pylori Infection Fulu Ai • Xiangdong Hua • Yefu Liu Jie Lin • Zhaoqiang Feng
•
Ó Springer Science+Business Media New York 2014
Abstract Little is known about the relationship about Helicobacter pylori (H. pylori) infection and pancreatic, and this study was set to investigate how H. pylori infection is correlated with pancreatic cancer and provide references for the clinical prevention and treatment of pancreatic cancer. 56 cases of pancreatic cancer patients admitted to the hospital from August 2012 to August 2013 were collected as the observation group. The anti-Hp IgG (H. pylori-specific antibodies), Hp IgM (H. pylori antibodies), and CagA-Hp-IgG (H. pylori serotoxin-associated protein a antibody) in the serum were measured and compared with the related indicators of control group (60 cases of healthy subjects). The H. pylori infection rate was 64.29 % in the observation group, and that in the control group was 46.67 %. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P \ 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53 % in the control group, for which the observation group was significantly higher than the control group (P \ 0.05). The occurrence of H. pylori infection in patients with pancreatic cancer was also positively correlated with the smoking history and the history of chronic pancreatitis (P \ 0.05). Helicobacter pylori infection is one of the risk factors for pancreatic cancer, and the patients with positive CagA-Hp have the higher risk, so the prevention and treatment of H. pylori infection would be beneficial for the prevention and treatment of pancreatic cancer.
F. Ai (&) X. Hua Y. Liu J. Lin Z. Feng Department of Hepato-Biliary-Pancreatic Surgery, Liaoning Cancer Hospital & Institute, 44 Xiaoheyan Road, Dadong District, Shenyang 110042, China e-mail: [email protected]
Keywords Relevance
Pancreatic cancer Helicobacter infection
Introduction Pancreatic cancer is a highly malignant tumor, which often occurs in the elderly population. Epidemiological data showed that the incidence of pancreatic cancer in the developed countries is higher than that in the developing countries [1]. With the rapid economic development of our country, the improved living standards also change the diet structure dramatically; therefore, recent years have witnessed increasing incidence of pancreatic cancer. Studies have confirmed that the incidence of pancreatic cancer is correlated with smoking, heredity, high-fat diet, and chronic pancreatitis [2]. However, there are still very few published studies on the relationship between Helicobacter pylori (H. pylori), and pancreatic cancer. In this study, we analyzed the H. pylori infection in 56 patients with pancreatic cancer in order to determine the relationship between H. pylori and pancreatic cancer, and provide references for the clinical prevention and treatment of pancreatic cancer. Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma [3], is the fifth leading cause of cancer-related death worldwide [4] and the fourth in the USA [5], due to the advanced stage at diagnosis and poor responses to current treatments [6]. Previous epidemiological investigations have identified some possible risk factors of pancreatic cancer, such as smoking, chronic pancreatitis, long-standing diabetes, mutations of various genes, and so on [7–9]. Although the infection with H. pylori has been implicated in the etiopathogenesis of various malignant conditions, its
123
Cell Biochem Biophys
etiological association with pancreatic cancer remains inconclusive [10]. Also some epidemiologic evidence suggests that H. pylori might be involved in the pathogenesis of pancreatic cancer, although the results have not been consistent across the studies [11–16]; therefore, we will investigate the relationship between pancreatic cancer and H. pylori infection.
Materials and Methods General Materials A total of 56 pancreatic cancer patients treated in our hospital from August 2012 to August 2013 were collected as the observation group. The inclusion criteria [3], the patients with clinical symptoms of abdominal pain and jaundice, abnormal laboratory performance, and two or more than two imaging support, excluded the patients with the diseases of complicated pancreatic benign lesions and cholangiocarcinoma. Among the 56 patients, 38 patients were male and 28 female, with the ages of 26–69 years, and the average age was (56.8 ± 6.75) year old. Twenty-six patients were diagnosed by surgery and pathological diagnosis, and 30 patients were diagnosed by clinical diagnosis. Another 60 healthy subjects were collected in the same period, including 35 male subjects and 25 female subjects, with the age of 22–68 years old, and the average age was (54.6 ± 7.35) year old. There were no significant differences in the gender, age, and other general information between two groups (P [ 0.05). Methods The gender, age, histories of hypertension, diabetes mellitus, drinking, smoking, biliary disease, chronic pancreatitis, and other information of all the subjects were investigated and registered, and then recorded in entry form. For serum detection, 3 ml venous blood was collected from all the subjects. The serum was separated, and anti-Hp IgG and IgM antibodies were detected in serum with enzyme-linked immunosorbent assay (ELISA), and the regents used in the detection were purchased from Zhongshan Biological Engineering Co., Ltd. Samples positive for anti-Hp IgG and Hp IgM, in the ELISA assay, were then subjected to the detection of the CagA-Hp-IgG with immunobiotting test (IBT). Helicobacter pylori strain typing was also performed, with the regents provided by Shanghai Yuangu Science and Technology Development Co., Ltd.
Table 1 Comparison of Hp antibody positive rate between the two groups (n, %) Indicators
Observation group (n = 56)
Control group (n = 60)
n
Positive rate
n
Positive rate
HP IgG (?)
31
55.35
16
26.67
HP IgM (?)
3
5.36
8
13.33
Hp IgG/IgM (?)
2
3.58
4
6.67
Total
36
64.29
28
46.67
v2
P
13.635
0.0012
Table 2 Association between pancreatic cancer and the risk factors of Hp infection, as well as the positive rate of anti-Hp (%) Indicators Gender Age (year)
N
Positive number
Positive rate
v2
P
1.362
0.075
1.433
0.068
1.373
0.073
1.621
0.068
Male
38
21
55.26
Female
28
15
53.57
B60
24
16
66.67
[60
32
20
62.5
History of hypertension
Yes
23
15
65.22
No
33
21
63.64
History of diabetes
Yes
12
8
66.67
No
44
28
63.63
Drinking history
Yes
26
16
61.54
1.732
0.063
No Yes
30 39
20 30
66.67 76.92
6.325
0.0032
No
17
6
35.29
History of biliary disease
Yes
15
9
60.00
1.835
0.058
No
41
27
64.85
History of chronic pancreatitis
Yes
20
15
75.00
4.236
0.028
No
36
21
58.33
Smoking history
Yes represents there exist the history of the disease; No represents there does not exist the history of the disease
measured with v2, and the comparison of efficacy between groups was calculated with rank-sum test. The count data were represented with x ± S, t test was used to test the mean value, and P \ 0.05 was considered as statistically significant.
Results
Statistical Analysis
Comparison of H. pylori Antibody Positive Rate Between Two Groups
Data input and statistical analysis was performed by SPSS16.O software, the proportion between groups was
In the observation group, positive H. pylori antibodies were found in 36 cases, and the positive rate was 64.29 %. And
123
Cell Biochem Biophys
in the control group, 28 cases were positive with a positive rate of 46.67 %, which was significantly lower than the observation group. The difference was statistically significant between two groups (P \ 0.01, Table 1). The positive rate of CagA-Hp among the subjects positive for H. pylori antibodies was 38.88 % (14/36), while that in the control group was 21.53 % (6/28). Therefore, the positive rate in the observation group was significantly higher than that in the control group, which was statistically different between two groups (v2 = 6.357, P \ 0.05). Our results indicated that the subjects with positive CagA-Hp have the higher risk of pancreatic cancer. Association Between Hp Infection and Risk Factors of Pancreatic Cancer Statistical results showed that the incidence of H. pylori infection in the pancreatic cancer was associated with the smoking history and chronic pancreatitis (P \ 0.05, Table 2).
Discussion Pancreatic cancer is one of the most highly malignant tumors, which is difficult to diagnose in the early stage due to the shortage of typical, and the surrounding tissue invasion and distant metastasis. Diagnosis in the later stages often leads to poor prognosis [17]. For the risk factors of pancreatic cancer, there is no exact clinical definition, and pancreatic cancer is generally thought to be associated with chronic pancreatitis, diabetes, smoking history, genetics, and high-fat diet [18]. The diagnosis of pancreatic cancer requires the combination of a variety of several laboratory tests, clinical symptoms, and imaging tests, such as the combination of percutaneous or endoscopic ultrasound, CT, ERCP, MRI, MRCP, PET, and other imaging studies. The 56 cases of pancreatic cancer patients in this study were diagnosed by the comprehensive consideration of clinical symptoms, laboratory tests, and imaging tests. Recently, studies have showed that H. pylori infection is closely related with the occurrence of pancreatic cancer, which led to the discoveries on the association between H. pylori infection and other gastrointestinal tumors by other researchers [19]. Some domestic studies showed that there was certain association between H. pylori infection and the occurrence and development of pancreatic cancer, but there was no clear conclusion on H. pylori infection as the risk factor of pancreatic cancer occurrence and development. So further in-depth studies on the relationship between H. pylori infection and pancreatic cancer can benefit the clinical prevention and treatment of pancreatic cancer [20].
In this study, H. pylori antibody positivity was found in 36 cases (64.29 %) in the observation group, and 28 cases (46.67 %) were positive for H. pylori antibodies. The positive rate of the observation group was significantly higher than that of the control group, and it was statistically different between two groups (P \ 0.01). The positive rate of CagA-Hp among all the cases positive for H. pylori antibodies in the observation group was 38.88 % (14/36), and 21.53 % (6/28) in the control group. The positive rate in the observation group was also significantly higher than that in the control group statistically (v2 = 6.357, P \ 0.05), indicating that the subjects positive for CagAHp have the higher risk of pancreatic cancer. Because of the proximity between pancreas, duodenum, and gastrointestinal tract, as well as the mutual influence in pathology and physiology, H. pylori likely can cause physiological changes of digestive tract, thereby induce the occurrence of exocrine pancreatic diseases, and lead to pancreatic cancer. Some studies have showed that the H. pylori DNA was found in the infected gastric antrum and the gastric body tissues, but the conclusion that H. pylori infection causes pancreatic cancer has not been proven [21]. Therefore, the mechanism of H. pylori infection in the occurrence and development of pancreatic cancer may be as follows: (1) The inflammation and tissue damages caused by H. pylori infection may decrease the somatostatin secretion, and decreased somatostatin weakens the inhibitory effect of antral G cells on gastrin release. Thus, gastroduodenal acid will be increased and lead to the proliferation of pancreatic ductal epithelial cells. Impaired DNA repair may follow the increased DNA duplication, and finally lead to pancreatic carcinogenesis under the influence of carcinogen [22]. The increased gastric H. pylori colonization and growth may result in reduced gastric acid, which can provide amenable environment for accelerated bacterial growth, and catalyze the nitrate to nitrous acid. This will promote the production of nitroso compounds, the strong carcinogens. But the ascorbic acid concentration is low in the patients with H. pylori infection, which may decrease the scavenging ability of nitrite and nitroso compounds; therefore, the pancreatic epithelial cells turn cancerous in the presence of carcinogens [23]. Helicobacter pylori changes its morphology according to the environment and enters into the master cells of the patients to avoid the immune attack. Helicobacter pylori adhere to the nuclear membrane and incorporate its DNA into the chromosomes through nuclear pores to induce carcinogenesis. Smoking and chronic pancreatitis are the risk factors of pancreatic cancer. This study showed that H. pylori infection in the patients with pancreatic cancer is associated with the history of smoking and chronic pancreatitis (P \ 0.05). Smoking can increase the incidence of H.
123
Cell Biochem Biophys
pylori infection, and promote pancreatic cancer, while the incidence of H. pylori infection in the patients with history of chronic pancreatitis was higher than that in the patients without such history, indicating that H. pylori can promote chronic pancreatitis to develop into pancreatic cancer. In brief, H. pylori infection is one of the risk factors for pancreatic cancer, and patients with CagA-Hp positivity have higher risk for pancreatic cancer. In conclusion, the improved prevention and treatment of H. pylori infection has great value for the prevention and treatment of pancreatic cancer.
References 1. Xu, P., Huang, Q., Liu, C. H., et al. (2011). Risk factors for pancreatic cancer: A case–control study. Tumor, 31(7), 653–657. 2. Dou, Y. C., & Wang, J. B. (2008). Detection of H. pylori infection in patients with pancreatic cancer and clinical significance. Journal of Jilin University (Medicine Edition), 34(2), 317–319. 3. Hidalgo, M. (2010). Pancreatic cancer. New England Journal of Medicine, 362, 1605–1617. 4. Hassan, M. M., Bondy, M. L., Wolff, R. A., Abbruzzese, J. L., Vauthey, J. N., et al. (2007). Risk factors for pancreatic cancer: Case–control study. American Journal of Gastroenterology, 102, 2696–2707. 5. Lowenfels, A. B., & Maisonneuve, P. (2002). Epidemiologic and etiologic factors of pancreatic cancer. Hematology/Oncology Clinics of North America, 16, 1–16. 6. Kang, R., & Tang, D. (2012). Autophagy in pancreatic cancer pathogenesis and treatment. American Journal of Cancer Research, 2, 383–396. 7. Raimondi, S., Maisonneuve, P., & Lowenfels, A. B. (2009). Epidemiology of pancreatic cancer: An overview. Nature Reviews Gastroenterology and Hepatology, 6, 699–708. 8. Wu, C., Miao, X., Huang, L., Che, X., Jiang, G., et al. (2012). Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nature Genetics, 44, 62–66. 9. Zhang, X., Zhong, R., Zhang, Z., Yuan, J., Liu, L., et al. (2011). Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer. Molecular Carcinogenesis, 50, 876–883. 10. Trikudanathan, G., Philip, A., Dasanu, C. A., & Baker, W. L. (2011). Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. JOP, 12(1), 26–31.
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11. Raderer, M., Wrba, F., Kornek, G., Maca, T., Koller, D. Y., Weinlaender, G., et al. (1998). Association between Helicobacter pylori infection and pancreatic cancer. Oncology, 55, 16–19. 12. Stolzenberg-Solomon, R. Z., Blaser, M. J., Limburg, P. J., PerezPerez, G., Taylor, P. R., Virtamo, J., et al. (2001). Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. Journal of the National Cancer Institute, 93, 937–941. 13. Lindkvist, B., Johansen, D., Borgstro¨m, A., & Manjer, J. (2008). A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer. BMC Cancer, 8, 321. 14. de Martel, C., Llosa, A. E., Friedman, G. D., Vogelman, J. H., Orentreich, N., Stolzenberg-Solomon, R. Z., et al. (2008). Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol Biomarkers Prevention, 17, 1188–1194. 15. Risch, H. A., Yu, H., Lu, L., & Kidd, M. S. (2010). ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: A case–control study. Journal of the National Cancer Institute, 102, 502–505. 16. Wadstrom, T., Fryzek, J. P., Demirjian, S., Choi, J. W., Garabrant, D. H., Nyren, O., et al. (2004). Antibodies to Helicobacter bills in patients with pancreatic carcinoma. Helicobacter, 9, 538. 17. Jesnowski, R., Isaksson, B., Mo¨hrcke, C., Bertsch, C., Bulajic, M., Schneider-Brachert, W., et al. (2010). Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. Pancreatology, 4, 462–466. 18. Nakayama, M., Iwakiri, R., Hara, M., Ootani, H., Shimoda, R., Tsunada, S., et al. (2009). Low-dose aspirin is a prominent cause of bleeding ulcers in patients who underwent emergency endoscopy. Journal of Gastroenterology, 44(9), 912–918. 19. Wang, G. Y., Huang, X. H., & Wu, G. P. (2009). Influence of Helicobacter pylori infection on serum IL-6, IL-8 and NO in duodenal ulcer patients. Journal of Hainan Medical College, 15(8), 45–47. 20. Tang, J. H., & Lv, N. H. (2008). A study on the relationship of Helicobacter pylori and vitamin C to gastric mucosa lesions. Chinese Journal of Postgraduates of Medicine, 31(10), 23–25. 21. Shimizu, S., Nakamura, S., Kishino, M., Konishi, H., & Shiratori, K. (2009). Role of antithrombotic therapy and nonsteroidal antiinflammatory drug use in bleeding gastroduodenal ulcers. Internal Medicine, 48(9), 631–637. 22. Lee, S. W., Chang, C. S., Lee, T. Y., Yeh, H. Z., Tung, C. F., & Peng, Y. C. (2010). Risk factors and therapeutic response in Chinese patients with peptic ulcer disease. World Journal of Gastroenterology, 16(16), 2017–2022. 23. Sokic-Milutinovic, A., Krstic, M., Rozer-Smolovic, B., & Alempijevic, T. (2010). Role of Helicobacter pylori infection in gastroduodenal damage in patients starting NSAID therapy: 4 Months follow-up study. Digestive Diseases and Sciences, 55(10), 2887–2892.
ORIGINAL PAPER
Preliminary Study of Pancreatic Cancer Associated with Helicobacter pylori Infection Fulu Ai • Xiangdong Hua • Yefu Liu Jie Lin • Zhaoqiang Feng
•
Ó Springer Science+Business Media New York 2014
Abstract Little is known about the relationship about Helicobacter pylori (H. pylori) infection and pancreatic, and this study was set to investigate how H. pylori infection is correlated with pancreatic cancer and provide references for the clinical prevention and treatment of pancreatic cancer. 56 cases of pancreatic cancer patients admitted to the hospital from August 2012 to August 2013 were collected as the observation group. The anti-Hp IgG (H. pylori-specific antibodies), Hp IgM (H. pylori antibodies), and CagA-Hp-IgG (H. pylori serotoxin-associated protein a antibody) in the serum were measured and compared with the related indicators of control group (60 cases of healthy subjects). The H. pylori infection rate was 64.29 % in the observation group, and that in the control group was 46.67 %. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P \ 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53 % in the control group, for which the observation group was significantly higher than the control group (P \ 0.05). The occurrence of H. pylori infection in patients with pancreatic cancer was also positively correlated with the smoking history and the history of chronic pancreatitis (P \ 0.05). Helicobacter pylori infection is one of the risk factors for pancreatic cancer, and the patients with positive CagA-Hp have the higher risk, so the prevention and treatment of H. pylori infection would be beneficial for the prevention and treatment of pancreatic cancer.
F. Ai (&) X. Hua Y. Liu J. Lin Z. Feng Department of Hepato-Biliary-Pancreatic Surgery, Liaoning Cancer Hospital & Institute, 44 Xiaoheyan Road, Dadong District, Shenyang 110042, China e-mail: [email protected]
Keywords Relevance
Pancreatic cancer Helicobacter infection
Introduction Pancreatic cancer is a highly malignant tumor, which often occurs in the elderly population. Epidemiological data showed that the incidence of pancreatic cancer in the developed countries is higher than that in the developing countries [1]. With the rapid economic development of our country, the improved living standards also change the diet structure dramatically; therefore, recent years have witnessed increasing incidence of pancreatic cancer. Studies have confirmed that the incidence of pancreatic cancer is correlated with smoking, heredity, high-fat diet, and chronic pancreatitis [2]. However, there are still very few published studies on the relationship between Helicobacter pylori (H. pylori), and pancreatic cancer. In this study, we analyzed the H. pylori infection in 56 patients with pancreatic cancer in order to determine the relationship between H. pylori and pancreatic cancer, and provide references for the clinical prevention and treatment of pancreatic cancer. Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma [3], is the fifth leading cause of cancer-related death worldwide [4] and the fourth in the USA [5], due to the advanced stage at diagnosis and poor responses to current treatments [6]. Previous epidemiological investigations have identified some possible risk factors of pancreatic cancer, such as smoking, chronic pancreatitis, long-standing diabetes, mutations of various genes, and so on [7–9]. Although the infection with H. pylori has been implicated in the etiopathogenesis of various malignant conditions, its
123
Cell Biochem Biophys
etiological association with pancreatic cancer remains inconclusive [10]. Also some epidemiologic evidence suggests that H. pylori might be involved in the pathogenesis of pancreatic cancer, although the results have not been consistent across the studies [11–16]; therefore, we will investigate the relationship between pancreatic cancer and H. pylori infection.
Materials and Methods General Materials A total of 56 pancreatic cancer patients treated in our hospital from August 2012 to August 2013 were collected as the observation group. The inclusion criteria [3], the patients with clinical symptoms of abdominal pain and jaundice, abnormal laboratory performance, and two or more than two imaging support, excluded the patients with the diseases of complicated pancreatic benign lesions and cholangiocarcinoma. Among the 56 patients, 38 patients were male and 28 female, with the ages of 26–69 years, and the average age was (56.8 ± 6.75) year old. Twenty-six patients were diagnosed by surgery and pathological diagnosis, and 30 patients were diagnosed by clinical diagnosis. Another 60 healthy subjects were collected in the same period, including 35 male subjects and 25 female subjects, with the age of 22–68 years old, and the average age was (54.6 ± 7.35) year old. There were no significant differences in the gender, age, and other general information between two groups (P [ 0.05). Methods The gender, age, histories of hypertension, diabetes mellitus, drinking, smoking, biliary disease, chronic pancreatitis, and other information of all the subjects were investigated and registered, and then recorded in entry form. For serum detection, 3 ml venous blood was collected from all the subjects. The serum was separated, and anti-Hp IgG and IgM antibodies were detected in serum with enzyme-linked immunosorbent assay (ELISA), and the regents used in the detection were purchased from Zhongshan Biological Engineering Co., Ltd. Samples positive for anti-Hp IgG and Hp IgM, in the ELISA assay, were then subjected to the detection of the CagA-Hp-IgG with immunobiotting test (IBT). Helicobacter pylori strain typing was also performed, with the regents provided by Shanghai Yuangu Science and Technology Development Co., Ltd.
Table 1 Comparison of Hp antibody positive rate between the two groups (n, %) Indicators
Observation group (n = 56)
Control group (n = 60)
n
Positive rate
n
Positive rate
HP IgG (?)
31
55.35
16
26.67
HP IgM (?)
3
5.36
8
13.33
Hp IgG/IgM (?)
2
3.58
4
6.67
Total
36
64.29
28
46.67
v2
P
13.635
0.0012
Table 2 Association between pancreatic cancer and the risk factors of Hp infection, as well as the positive rate of anti-Hp (%) Indicators Gender Age (year)
N
Positive number
Positive rate
v2
P
1.362
0.075
1.433
0.068
1.373
0.073
1.621
0.068
Male
38
21
55.26
Female
28
15
53.57
B60
24
16
66.67
[60
32
20
62.5
History of hypertension
Yes
23
15
65.22
No
33
21
63.64
History of diabetes
Yes
12
8
66.67
No
44
28
63.63
Drinking history
Yes
26
16
61.54
1.732
0.063
No Yes
30 39
20 30
66.67 76.92
6.325
0.0032
No
17
6
35.29
History of biliary disease
Yes
15
9
60.00
1.835
0.058
No
41
27
64.85
History of chronic pancreatitis
Yes
20
15
75.00
4.236
0.028
No
36
21
58.33
Smoking history
Yes represents there exist the history of the disease; No represents there does not exist the history of the disease
measured with v2, and the comparison of efficacy between groups was calculated with rank-sum test. The count data were represented with x ± S, t test was used to test the mean value, and P \ 0.05 was considered as statistically significant.
Results
Statistical Analysis
Comparison of H. pylori Antibody Positive Rate Between Two Groups
Data input and statistical analysis was performed by SPSS16.O software, the proportion between groups was
In the observation group, positive H. pylori antibodies were found in 36 cases, and the positive rate was 64.29 %. And
123
Cell Biochem Biophys
in the control group, 28 cases were positive with a positive rate of 46.67 %, which was significantly lower than the observation group. The difference was statistically significant between two groups (P \ 0.01, Table 1). The positive rate of CagA-Hp among the subjects positive for H. pylori antibodies was 38.88 % (14/36), while that in the control group was 21.53 % (6/28). Therefore, the positive rate in the observation group was significantly higher than that in the control group, which was statistically different between two groups (v2 = 6.357, P \ 0.05). Our results indicated that the subjects with positive CagA-Hp have the higher risk of pancreatic cancer. Association Between Hp Infection and Risk Factors of Pancreatic Cancer Statistical results showed that the incidence of H. pylori infection in the pancreatic cancer was associated with the smoking history and chronic pancreatitis (P \ 0.05, Table 2).
Discussion Pancreatic cancer is one of the most highly malignant tumors, which is difficult to diagnose in the early stage due to the shortage of typical, and the surrounding tissue invasion and distant metastasis. Diagnosis in the later stages often leads to poor prognosis [17]. For the risk factors of pancreatic cancer, there is no exact clinical definition, and pancreatic cancer is generally thought to be associated with chronic pancreatitis, diabetes, smoking history, genetics, and high-fat diet [18]. The diagnosis of pancreatic cancer requires the combination of a variety of several laboratory tests, clinical symptoms, and imaging tests, such as the combination of percutaneous or endoscopic ultrasound, CT, ERCP, MRI, MRCP, PET, and other imaging studies. The 56 cases of pancreatic cancer patients in this study were diagnosed by the comprehensive consideration of clinical symptoms, laboratory tests, and imaging tests. Recently, studies have showed that H. pylori infection is closely related with the occurrence of pancreatic cancer, which led to the discoveries on the association between H. pylori infection and other gastrointestinal tumors by other researchers [19]. Some domestic studies showed that there was certain association between H. pylori infection and the occurrence and development of pancreatic cancer, but there was no clear conclusion on H. pylori infection as the risk factor of pancreatic cancer occurrence and development. So further in-depth studies on the relationship between H. pylori infection and pancreatic cancer can benefit the clinical prevention and treatment of pancreatic cancer [20].
In this study, H. pylori antibody positivity was found in 36 cases (64.29 %) in the observation group, and 28 cases (46.67 %) were positive for H. pylori antibodies. The positive rate of the observation group was significantly higher than that of the control group, and it was statistically different between two groups (P \ 0.01). The positive rate of CagA-Hp among all the cases positive for H. pylori antibodies in the observation group was 38.88 % (14/36), and 21.53 % (6/28) in the control group. The positive rate in the observation group was also significantly higher than that in the control group statistically (v2 = 6.357, P \ 0.05), indicating that the subjects positive for CagAHp have the higher risk of pancreatic cancer. Because of the proximity between pancreas, duodenum, and gastrointestinal tract, as well as the mutual influence in pathology and physiology, H. pylori likely can cause physiological changes of digestive tract, thereby induce the occurrence of exocrine pancreatic diseases, and lead to pancreatic cancer. Some studies have showed that the H. pylori DNA was found in the infected gastric antrum and the gastric body tissues, but the conclusion that H. pylori infection causes pancreatic cancer has not been proven [21]. Therefore, the mechanism of H. pylori infection in the occurrence and development of pancreatic cancer may be as follows: (1) The inflammation and tissue damages caused by H. pylori infection may decrease the somatostatin secretion, and decreased somatostatin weakens the inhibitory effect of antral G cells on gastrin release. Thus, gastroduodenal acid will be increased and lead to the proliferation of pancreatic ductal epithelial cells. Impaired DNA repair may follow the increased DNA duplication, and finally lead to pancreatic carcinogenesis under the influence of carcinogen [22]. The increased gastric H. pylori colonization and growth may result in reduced gastric acid, which can provide amenable environment for accelerated bacterial growth, and catalyze the nitrate to nitrous acid. This will promote the production of nitroso compounds, the strong carcinogens. But the ascorbic acid concentration is low in the patients with H. pylori infection, which may decrease the scavenging ability of nitrite and nitroso compounds; therefore, the pancreatic epithelial cells turn cancerous in the presence of carcinogens [23]. Helicobacter pylori changes its morphology according to the environment and enters into the master cells of the patients to avoid the immune attack. Helicobacter pylori adhere to the nuclear membrane and incorporate its DNA into the chromosomes through nuclear pores to induce carcinogenesis. Smoking and chronic pancreatitis are the risk factors of pancreatic cancer. This study showed that H. pylori infection in the patients with pancreatic cancer is associated with the history of smoking and chronic pancreatitis (P \ 0.05). Smoking can increase the incidence of H.
123
Cell Biochem Biophys
pylori infection, and promote pancreatic cancer, while the incidence of H. pylori infection in the patients with history of chronic pancreatitis was higher than that in the patients without such history, indicating that H. pylori can promote chronic pancreatitis to develop into pancreatic cancer. In brief, H. pylori infection is one of the risk factors for pancreatic cancer, and patients with CagA-Hp positivity have higher risk for pancreatic cancer. In conclusion, the improved prevention and treatment of H. pylori infection has great value for the prevention and treatment of pancreatic cancer.
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