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Role of smoking and helicobacter pylori infection in aetiology of cardia versus non-cardia gastric cancer
April 2000
AGAA759
4084
4086
SEROPREVALENCE OF H. PYLORI, CAGA AND INCIDENCE OF GASTRIC CANCER IN A MULTI·ETHNIC POPULATION, Kwong Ming Fock, Suok Kai Chew, Christopher Jl Khor, Subbiah Dhamodaran, Jeffrey Cutter, Tay Meng Ng, Eng Kiong Teo, Tju Siang Chua, Yin Mei Lee, Changi Gen Hosp, Singapore, Singapore; Ministry of Health, Singapore, Singapore. Introduction: HPylori infection (especailly with CagA positive strain) is believed to be associated with an increased risk of developing gastric carcinoma. We have previously demonstrated that racial difference in gastric cancer risk in the 3 ethnic groups in Singapore (Chinese, Malay and Indians)could be correlated with Hpylori seroprevalence in the case of Chinese and Malays but not in Indians living in Singapore. Aim: This study aims to determine if the ethnic difference in gastric cancer risk could be explained on the basis of CagA positivity. Method: In 1998, a randomised health survey of 11,000 household was conducted in Singapore, and 7,000 persons aged 18-69 were invited to participate in a health screening. From this group, fifty specimens of blood were taken from each gender and ethnic group from ages 25-39 years and 55-65 years. This data was related to the incidence rate of gastric cancer in these ethnic groups obtained from the Singapore Cancer Registry using linear regression. Results : The seroprevalence of HPylori infection by ethnic group was 47.3% in Chinese, 24.3% in Malays and 47.6% in Indians. The age standardised cancer incidence was 23.5 per 100,000 in Chinese males, 6.0 in Malay males and 11.2 in Indian males. The incidence rates for females were 14.7,3.8, 11.2 respectively. There was a correlation between H.pylori seroprevalence and gastric cancer incidence for Chinese and Malays but not for Indians. Pearson's correlation coefficient (r) was 0.937 (p=O.03). The seroprevalence of CagA was 75.8% in Chinese, 93.5% in Malays and 76.1% in Indians and the difference was not statistically significant. Conclusion: It was concluded that the difference in gastric cancer incidence between the ethnic groups in Singapore was not due to differences in seroprevalence of CagA.
IS THERE AN OBLIGATORY NEED FOR AN ONCOLOGICAL TREATMENT MODALITY IF HELICOBACTER PYLORI ERAD· ICATION IS NOT FOLLOWED BY COMPLETE REGRESSION OF GASTRIC LOW·GRADE LYMPHOMA OF MALT·TYPE? Maria-Elisabeth Kolve-Goebeler, Wolfgang Fischbach, Medicine Poliklinik, Univ of Wuerzburg, Wuerzburg, Germany; Dept of Internal Medicine, Clin Aschaffenburg, Aschaffenburg, Germany. Background: Helicobacter pylori (Hp) eradication is the well accepted initial treatment of localized low-grade gastric lymphoma offering success rates of about 80%. Treatment failure is usually defined if there is no complete regression of the lymphoma within 12 months. In this case, surgery or radiotherapy is the favored therapeutic approach. We, here, report our experience with seven patients revealing minor residual lymphoma 12 months after Hp eradication and refusing any further therapy. Methods: Seven patients, two female and five male, mean age 55 years (range 43-69) were diagnosed to have low-grade gastric lymphoma of MALT-type (marginal zone B-cell lymphoma according to the REAL classification) by centralized histologic review. Complete diagnostic work-up including abdominal and cervical ultrasound, CT scan of the chest and abdomen, bone marrow puncture and endoscopic ultrasound revealed stage EI according to the Ann Arbor staging system modified by Musshoff in all cases. Triple therapy using omeprazole, metronidazole and clarithromycin was performed and all patients became Hp negative as demonstrated by urease test and histology. The patients were investigated endoscopicbioptically three-monthly. They were classified as non-responders to Hperadication due to persisting lymphoma infiltrates after 12 months. All refused the proposed surgical resection or radiation despite extensive information. However, they agreed in a regular endoscopic follow-up. Results: While the endoscopic findings were normal or revealed features of discrete post-Hp-gastritis minimal residual lymphoma infiltrates were detected histologically at any control. There were no signs of lymphoma progression in 6/7 patients within observation periods of 14, 18,20,21,25 and 28 months, respectively. One patient developed an upper abdominal mass causing ileus five years after primary diagnosis. Surgical resection material confirmed lymph node involvement by the low-grade MALT lymphoma. Conclusions: Patients with minimal residuals of low-grade gastric MALT lymphoma after Hp eradication may have a favourable course of disease. Surgery and/or radiotherapy may, therefore, be postponed in the individual case on condition that a close follow-up is performed.
4085 ROLE OF SMOKING AND HEUCOBACTER PYLORI INFECTION IN AETIOLOGY OF CARDIA VERSUS NON·CARDIA GASTRIC CANCER. Svein Hansen, K K Melby, S. Aase, E. Jellum, Kenneth E. McColl, S. E. Vollset, Cancer Registry of Norway, Oslo, Norway; Bergen, Norway; Univ of Glasgow, Glasgow, United Kingdom; Bergen. OBJECTIVE: To study the role of smoking and H pylori in cardia cancer (CC) and non-cardia gastric cancer (NCGC). METHODS: Nested casecontrol study based on 101,601 individuals from the Norwegian JANUS cohort. Two controls were matched by age, sex, date of serum sampling, and serum source to each of 41 CC cases and 123 NCGC cases. Serum stored frozen a median of 12.1 years since collection was tested for anti-H.pylori antibodies. Each subject was classified as current smoker or non-smoker at the time of serum sampling. RESULTS: The risk of cardia cancer in H. pylori seropositive subjects was reduced by a factor of 3.6 relative to seronegative subjects before adjustment for smoking and by a factor of 4.8 after adjustment. H pylori seropositivity increased the risk of NCGC by a factor of 5.0 and was unchanged after adjustment for smoking. After adjustment for H. pylori status, smoking more than doubled the risk of both CC and NCGC. For each cancer type the combined relative risks of smoking and H pylori seropositivity roughly equalled the product of the relative risks associated with each factor alone. CONCLUSION: H. pylori infection was associated with a 5-fold increased risk of NCGC and 5-fold reduced risk of CC. Smoking more than doubled the risk of both cancers. RESULTS:
H.P.+vs H.P.·
CC NCGC
0.28(0.12-0.64) 4.97(2.50-9.88)
Values are odds ratios (95% Cf.)
H.P.+vs H.P.· adj Smoking vs nonSmoking vsnonforsmoking smoking smoke adjfor H.P. inf 0.21(0.08-054) 4.92(2.45-9.89)
1.36(062·2.97) 2.30(145-366)
2.24(0.88-5.73) 2.34(1.42-3.85)
4087 EXPRESSION OF APOPTOSIS RELATED PROTEINS BAX AND BCL·2 AND GROWTH FACTORS IN HUMAN GASTRIC ADENO· CARCINOMA. Peter Ch Konturek, Elzbieta Karczewska, T. Starzynska, K. Marlicz, Stanislaw Konturek, Eckhart Hahn, Dept of Medicine I, Erlangen, Germany; Inst of Physiology; Univ Sch of Medicine, Cracow, Poland; Dept of Gastroenterology, Pomeranian Med Acad, Szczecin, Poland; Dept of Medicine I, Univ Erlangen-Nuremberg, Erlangen, Germany. H.pylori (Hp) has been postulated to play an important role in the pathogenesis of gastric cancer(GC). We have shown previously that Hp infection is associated with increased expression of mucosal growth factors, increased mucosal apoptosis rate and enhanced mucosal cell proliferation which may contribute to the carcinogenesis. However, the changes in gene expression for growth factors such as hepatocyte growth factor (HGF), transforming growth factor alpha (TGFa) and apoptosis related proteins of bcl-2 family (bax and bcl-2) in gastric cancer have been little studied. Patients and Methods: 50 patients with GC (age range: 20-70 years) and 20 controls (age range: 16-60 years) were included in this study. The prevalence of Hp infection was assessed by serology and l3C-urea breath test. In addition, serum samples were assayed for CagA antibodies. The gene expression for HGF, TGFa, bax and bcl-2 was determined in biopsy specimens taken during endoscopy or surgery from tumor tissue and neighbouring nontumorous mucosa by reverse transcription polymerase chain reaction(RT-PCR) and quantified by densitometry. Finally, the mucosal gene expression and plasma level of !L-8 were determined by RT-PCR and ELISA Results: Hp infection rate among GC patients was significantly higher than among control patients (90% among GC patients vs.40% in control group). CagA antibodies were detected in GC patients more frequent(58.8% )than in controls (32%). The gene expression for HGF and TGFa was significantly higher in biopsy specimens taken from cancer as compared to those taken from neighbouring mucosa (HGF/GAPDH ratio: 0.72: 0.12 vs. 0.212:0.08). The expression of proapoptotic bax and antiapoptotic bcl-2 was higher in cancer tissue than in neighbouring mucosa. However, bcl-2 rnRNA expression was higher than bax mRNA expression in samples from cancer (bcl-2/GAPDH ratio: 0.642:0.17 vs. 0.412:0.023). Median plasma levels of IL-8 was significantly increased and this was accompanied by the stronger gene overexpression for IL-8 in cancer samples than in non-cancer mucosa. Conclusions: 1) Patients infected with Hp, especially with CagA positive strains, are at higher risk to develop gastric cancer; 2)The overexpression of growth factors such as HGF and TGFa contribute to the carcinogenesis; 3) The bax/bcl-2 system is upregulated in gastric cancer with more pronounced expression of bcl-2; 4) An enhanced gene expression and release oflL-8 probably results from increased inflammatory reaction to cancer in gastric mucosa.
AGAA759
4084
4086
SEROPREVALENCE OF H. PYLORI, CAGA AND INCIDENCE OF GASTRIC CANCER IN A MULTI·ETHNIC POPULATION, Kwong Ming Fock, Suok Kai Chew, Christopher Jl Khor, Subbiah Dhamodaran, Jeffrey Cutter, Tay Meng Ng, Eng Kiong Teo, Tju Siang Chua, Yin Mei Lee, Changi Gen Hosp, Singapore, Singapore; Ministry of Health, Singapore, Singapore. Introduction: HPylori infection (especailly with CagA positive strain) is believed to be associated with an increased risk of developing gastric carcinoma. We have previously demonstrated that racial difference in gastric cancer risk in the 3 ethnic groups in Singapore (Chinese, Malay and Indians)could be correlated with Hpylori seroprevalence in the case of Chinese and Malays but not in Indians living in Singapore. Aim: This study aims to determine if the ethnic difference in gastric cancer risk could be explained on the basis of CagA positivity. Method: In 1998, a randomised health survey of 11,000 household was conducted in Singapore, and 7,000 persons aged 18-69 were invited to participate in a health screening. From this group, fifty specimens of blood were taken from each gender and ethnic group from ages 25-39 years and 55-65 years. This data was related to the incidence rate of gastric cancer in these ethnic groups obtained from the Singapore Cancer Registry using linear regression. Results : The seroprevalence of HPylori infection by ethnic group was 47.3% in Chinese, 24.3% in Malays and 47.6% in Indians. The age standardised cancer incidence was 23.5 per 100,000 in Chinese males, 6.0 in Malay males and 11.2 in Indian males. The incidence rates for females were 14.7,3.8, 11.2 respectively. There was a correlation between H.pylori seroprevalence and gastric cancer incidence for Chinese and Malays but not for Indians. Pearson's correlation coefficient (r) was 0.937 (p=O.03). The seroprevalence of CagA was 75.8% in Chinese, 93.5% in Malays and 76.1% in Indians and the difference was not statistically significant. Conclusion: It was concluded that the difference in gastric cancer incidence between the ethnic groups in Singapore was not due to differences in seroprevalence of CagA.
IS THERE AN OBLIGATORY NEED FOR AN ONCOLOGICAL TREATMENT MODALITY IF HELICOBACTER PYLORI ERAD· ICATION IS NOT FOLLOWED BY COMPLETE REGRESSION OF GASTRIC LOW·GRADE LYMPHOMA OF MALT·TYPE? Maria-Elisabeth Kolve-Goebeler, Wolfgang Fischbach, Medicine Poliklinik, Univ of Wuerzburg, Wuerzburg, Germany; Dept of Internal Medicine, Clin Aschaffenburg, Aschaffenburg, Germany. Background: Helicobacter pylori (Hp) eradication is the well accepted initial treatment of localized low-grade gastric lymphoma offering success rates of about 80%. Treatment failure is usually defined if there is no complete regression of the lymphoma within 12 months. In this case, surgery or radiotherapy is the favored therapeutic approach. We, here, report our experience with seven patients revealing minor residual lymphoma 12 months after Hp eradication and refusing any further therapy. Methods: Seven patients, two female and five male, mean age 55 years (range 43-69) were diagnosed to have low-grade gastric lymphoma of MALT-type (marginal zone B-cell lymphoma according to the REAL classification) by centralized histologic review. Complete diagnostic work-up including abdominal and cervical ultrasound, CT scan of the chest and abdomen, bone marrow puncture and endoscopic ultrasound revealed stage EI according to the Ann Arbor staging system modified by Musshoff in all cases. Triple therapy using omeprazole, metronidazole and clarithromycin was performed and all patients became Hp negative as demonstrated by urease test and histology. The patients were investigated endoscopicbioptically three-monthly. They were classified as non-responders to Hperadication due to persisting lymphoma infiltrates after 12 months. All refused the proposed surgical resection or radiation despite extensive information. However, they agreed in a regular endoscopic follow-up. Results: While the endoscopic findings were normal or revealed features of discrete post-Hp-gastritis minimal residual lymphoma infiltrates were detected histologically at any control. There were no signs of lymphoma progression in 6/7 patients within observation periods of 14, 18,20,21,25 and 28 months, respectively. One patient developed an upper abdominal mass causing ileus five years after primary diagnosis. Surgical resection material confirmed lymph node involvement by the low-grade MALT lymphoma. Conclusions: Patients with minimal residuals of low-grade gastric MALT lymphoma after Hp eradication may have a favourable course of disease. Surgery and/or radiotherapy may, therefore, be postponed in the individual case on condition that a close follow-up is performed.
4085 ROLE OF SMOKING AND HEUCOBACTER PYLORI INFECTION IN AETIOLOGY OF CARDIA VERSUS NON·CARDIA GASTRIC CANCER. Svein Hansen, K K Melby, S. Aase, E. Jellum, Kenneth E. McColl, S. E. Vollset, Cancer Registry of Norway, Oslo, Norway; Bergen, Norway; Univ of Glasgow, Glasgow, United Kingdom; Bergen. OBJECTIVE: To study the role of smoking and H pylori in cardia cancer (CC) and non-cardia gastric cancer (NCGC). METHODS: Nested casecontrol study based on 101,601 individuals from the Norwegian JANUS cohort. Two controls were matched by age, sex, date of serum sampling, and serum source to each of 41 CC cases and 123 NCGC cases. Serum stored frozen a median of 12.1 years since collection was tested for anti-H.pylori antibodies. Each subject was classified as current smoker or non-smoker at the time of serum sampling. RESULTS: The risk of cardia cancer in H. pylori seropositive subjects was reduced by a factor of 3.6 relative to seronegative subjects before adjustment for smoking and by a factor of 4.8 after adjustment. H pylori seropositivity increased the risk of NCGC by a factor of 5.0 and was unchanged after adjustment for smoking. After adjustment for H. pylori status, smoking more than doubled the risk of both CC and NCGC. For each cancer type the combined relative risks of smoking and H pylori seropositivity roughly equalled the product of the relative risks associated with each factor alone. CONCLUSION: H. pylori infection was associated with a 5-fold increased risk of NCGC and 5-fold reduced risk of CC. Smoking more than doubled the risk of both cancers. RESULTS:
H.P.+vs H.P.·
CC NCGC
0.28(0.12-0.64) 4.97(2.50-9.88)
Values are odds ratios (95% Cf.)
H.P.+vs H.P.· adj Smoking vs nonSmoking vsnonforsmoking smoking smoke adjfor H.P. inf 0.21(0.08-054) 4.92(2.45-9.89)
1.36(062·2.97) 2.30(145-366)
2.24(0.88-5.73) 2.34(1.42-3.85)
4087 EXPRESSION OF APOPTOSIS RELATED PROTEINS BAX AND BCL·2 AND GROWTH FACTORS IN HUMAN GASTRIC ADENO· CARCINOMA. Peter Ch Konturek, Elzbieta Karczewska, T. Starzynska, K. Marlicz, Stanislaw Konturek, Eckhart Hahn, Dept of Medicine I, Erlangen, Germany; Inst of Physiology; Univ Sch of Medicine, Cracow, Poland; Dept of Gastroenterology, Pomeranian Med Acad, Szczecin, Poland; Dept of Medicine I, Univ Erlangen-Nuremberg, Erlangen, Germany. H.pylori (Hp) has been postulated to play an important role in the pathogenesis of gastric cancer(GC). We have shown previously that Hp infection is associated with increased expression of mucosal growth factors, increased mucosal apoptosis rate and enhanced mucosal cell proliferation which may contribute to the carcinogenesis. However, the changes in gene expression for growth factors such as hepatocyte growth factor (HGF), transforming growth factor alpha (TGFa) and apoptosis related proteins of bcl-2 family (bax and bcl-2) in gastric cancer have been little studied. Patients and Methods: 50 patients with GC (age range: 20-70 years) and 20 controls (age range: 16-60 years) were included in this study. The prevalence of Hp infection was assessed by serology and l3C-urea breath test. In addition, serum samples were assayed for CagA antibodies. The gene expression for HGF, TGFa, bax and bcl-2 was determined in biopsy specimens taken during endoscopy or surgery from tumor tissue and neighbouring nontumorous mucosa by reverse transcription polymerase chain reaction(RT-PCR) and quantified by densitometry. Finally, the mucosal gene expression and plasma level of !L-8 were determined by RT-PCR and ELISA Results: Hp infection rate among GC patients was significantly higher than among control patients (90% among GC patients vs.40% in control group). CagA antibodies were detected in GC patients more frequent(58.8% )than in controls (32%). The gene expression for HGF and TGFa was significantly higher in biopsy specimens taken from cancer as compared to those taken from neighbouring mucosa (HGF/GAPDH ratio: 0.72: 0.12 vs. 0.212:0.08). The expression of proapoptotic bax and antiapoptotic bcl-2 was higher in cancer tissue than in neighbouring mucosa. However, bcl-2 rnRNA expression was higher than bax mRNA expression in samples from cancer (bcl-2/GAPDH ratio: 0.642:0.17 vs. 0.412:0.023). Median plasma levels of IL-8 was significantly increased and this was accompanied by the stronger gene overexpression for IL-8 in cancer samples than in non-cancer mucosa. Conclusions: 1) Patients infected with Hp, especially with CagA positive strains, are at higher risk to develop gastric cancer; 2)The overexpression of growth factors such as HGF and TGFa contribute to the carcinogenesis; 3) The bax/bcl-2 system is upregulated in gastric cancer with more pronounced expression of bcl-2; 4) An enhanced gene expression and release oflL-8 probably results from increased inflammatory reaction to cancer in gastric mucosa.