endemic gastric cancer genetic susceptibility in western honduras

1
either NERD or mild erosive disease, but some may have underlying peptic ulcer disease or gastric cancer. ERD was associated with older age, male gender, higher body mass index, smoking, alcohol, and lower prevalence of minor psychiatric morbidity compared to NERD. Sl181 Quality of Life in a General Adult Population with Gastroesophageal Reflux Symptoms and/or Esophagitis. A Report from the Kalixanda Study Pertti Aro, Jukka Ronkainen, Tom Storskrubb, Elisabeth Bolling-Sternevald, Tore Lind, Hans Graffner, Nicholas J. Talley, Lars Agreus Background and Aims: It is well known that quality of life (QoL) is impaired in patients with symptomatic gastroesophageal reflux disease (GERD), but data are scarce for non- patients with GERD. For non-patients with esophagitis (E-it), no QoL data are available. The aim of this study was to determine QoL in a random sample of a Swedish adult population with or without esophagitis and GERD. Methods: A random sample (n = 3000, age 18-80 years, mean age 53.5, 51% women) of two northern Swedish municipalities (n=21 610) was surveyed using a validated GI symptom questionnaire. A random sample of 1001 of the responders (n=2122, 71%) completed an esophagogastroduodenoscopy (EGD), 362 (23%) declined and 203 (13%) had contraindications. GERD was defined as the presence of troublesome heartburn and/or acid regurgitation during the past three months. E-it was defined as any grade of Los Angeles A-D. QoL was evaluated with SF-36 with the domains Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Mental Health (MH), Vitality (VT), Social Functioning (SF) and Role-Emotional (RE). Results: EGD was performed and an evahiable SF-36 was obtained in 999 subjects (mean age 53.5 years, 51.3% women). GERD was reported by 399 and E-it was found in 151 subjects (Los Angeles A n= 106, B n=38, C n=3 and D n=2 subjects, missing data n = 2). 97 (64.2%) of those with E-it had GERD symptoms, while 54 had not. In univariate analysis of SF-36, those with GERD had significantly lower scores in all domains except RE (p=0.07) compared to those without (the 54 subjects with symptom free E-it excluded). The 151 subjects with E-it had a significantly lower score only in the GH domain (p =0.02) compared to the 848 without E-it. 36 of the 151 had used acid reducing drugs (ARD: antacids, H2-blockers or PPI) and they had significantly lower scores in all domains except for BP. When comparing symptomatic (n=97) to asymptomatic E-it (n=54), the former scored significantly lower in GH, VT and MH. Among those with GERD symptoms, no significant difference was shown in any SF-36 domain between those with and those without E-ti. When introducing also age, sex, BM1 and the use of ARD within the past three months into a logistic regression analysis model, GERD remained an independent worsening predictor for all SF-36 domains except RE, while esophagitis did not. Conclusions: GERD symptoms affect QoL in an adult non-patient population, while E-it per se does not. $1182 Gastroesophageal Reflux Is More Prominent In Western Dyspeptics: A Prospective Comparison Study Of British and South East Asian Patients with Dyspepsia Sanjiv Mahadeva, Muthukarapan C. Raman, Mark Follows, Khean-Lee Goh, Anthony T. Axon, Paul Moayyedi BACKGROUND There is a paucity of data directly comparing the incidence of gastro- esophageal reflux disease (GERD) in Western and Eastern populations. We therefore com- pared clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and Asia in a cross-sectional study. METHODS Patients with uncomplicated dyspepsia attending endoscopy units in both institu- tions were prospectively interviewed and underwent subsequent endoscopy from January 1999 to June 2001 (Leeds, UK) and between January and August 2002 (Knafa Lumpur, Malaysia). RESULTS 693 patients from Kuala Lumpur and 392 patients from Leeds of Caucasian race were included in the analysis. The mean age was 48.7 +- 15.8 and 47.5 _+13.8 years for the Malaysian and British patients respectively (p = NS). There was a higher proportion of cigarette smoking (39.5% vs 13.4%, p< 0.0001), alcohol consumption (32.5% vs 2.5%, p < 0.0001), NSAID use (33.2% vs 23.4%, p=0.005) and H. pylori infection (45.3% vs 23.5%, p< 0.001) amongst the British patients. GERD symptoms were more common in British compared to Malaysian patients (heartburn (66.2% vs 37.4%), regurgita- tion (60.1% vs 30.2%) and dysphagia (23.7% vs 6.7%) p < 0.0001). This correlated to an increased endoscopic finding of refhix oesophagitis (29.6% vs 5.8%) and Barrett's oesophagus (3.8% vs 0.7%) amongst British patients (p< 0.001). A logistic regression model revealed that Caucasian race (OR 9.1; 95% CI =4.2 to 20.1), male sex (OR 2.0; 95% CI= 1.2 to 3.2) and H. pylori infection (OR 0.4; 95% CI = 0.2 to 0.6) were independent predictors for reflux oesophagitis. Heartburn had a 75% sensitivity and 38% specificity for detecting oesophagitis in British patients compared to a 45% sensitivity and 63% specificity in Malaysian patients. CONCLUSIONS GERD is more predominant in Western patients and their symp- toms are more predictive of pathology compared to their South East Asian counterparts. $1183 Ethnic Differences in Gastric Cancer in a Multiracial Asian Population: a Case- Control Study Khean-Lee Goh, Phaik-Leng Cheah, Md Noorfaridah, N. Parasakthi Background: Some of the highest incidences of gastric cancer have been reported in Asia with rates in excess of 80 per 100,00 population. However marked differences exist between different geographical regions and between different ethnic groups in Asia. Malaysia epito- mizes the muhiraciality of the Asian population with three major Asian races: Malay, Chinese and Indian living together. Objectives: To determine risk factors, particularly, ethnicity for gastric cancer in Malaysian patients Methods: A prospective age and sex-matched hospital based case-control study was performed at the University of Malaya Medical Center, Kuala Lumpur. Consecutive patients presenting with gastric cancer were recruited and subjected to a detailed questionnaire and had sera taken for H.pylori serology. H.pylori serology was performed using a locally validated serological test: HEL-p II test (AMRAD, Australia) which has been shown to have a high sensitivity and specificity. Controls were chosen from hospital patiems who did not have any gastric nor GIT diseases and were sex and age-matched in a ratio of 2:1. Comparisons between cases and comrols were made using X2 test. Multivariate analysis was performed using multiple logistic regression analysis. Results: Eighty-seven cases of gastric cancer and 174 controls were recruited for the study. The mean age of controls was 58.5 yrs and cases 61.4 yrs. Analysis of the prevalence of gastric cancer- Chinese vs Malay: p<0.001, odds ratio (OR) 13.6 (4.4,47.6) and vs Indian p<O.001 OR 5.5 (2.8,11.1). Following multiple logistic regression analysis, the following remained significant indepen- dent risk factors: Chinese race- OR 10.2 (2.9, 36.5), low education- 9.8 (2.0, 37.5), smoking- 2.5 (1.2, 5.1), low consumption of fresh fruits and vegetables- 6.6 (1.6, 28.2), frequent ingestion of salted foods- 5.2 (1.3, 20.0) and H.pylori infection- 2.5 (1.2, 5.6). Conclusions: The role of ethnicity in predicting gastric cancer in our multiracial population is interesting. Chinese race had a higher risk compared to the two other major races in the country: Malays and Indians. $1184 Endemic Gastric Cancer Genetic Susceptibility in Western Honduras Douglas Morgan, Ricardo Dominguez, Temitope Keku, Paris Heidt, Darn McGinn BACKROUND. Gastric cancer is the second leading cause of cancer mortality in the world with significant geographic variability, lnterleukin-lB genotypes (-511T, -31T, -RN*2) are associated in H. pylori infected patients in Europe and Asia. The backround prevalence of polymorphisms in these populations ranges 50-70% (-511T; CT, 39-50%; TT, 11-21%). A systematic evaluation of gastric cancer risk factors (genetic, bacterial, dietary) in a popufation- based design is lacking. METHODS. The current study is a prospective, population-based, case-control design in western Honduras, Central America. The western region of Honduras (half million population, 95% Hispanic mestizo) is identified as a high incidence region in a recent 10 year survey. The estimated standardized gastric cancer incidence rate for the year 2000 was 39 and 21 for males and females, respectively (per 100,000 world standard population). 25% and 12% of cases were less than ages of 50 and 35, respectively. In the current study, gastric cancer cases were enrolled in prospective fashion from the Western Regional Hospital. Satellite imagery from the Community Development Department facili- tated a population-based approach to comrol recruitment. Controls were balanced among the sexes and age ranges (18-34, 35-49, 50-64, >65). Genomic DNA was obtained from whole blood per protocol(Gentra Systems) H. pylori status was established by EL1SA. Gastric cancer cases were confirmed by histology. The image-based DietHistory was used to establish dietary and micronutrient intake. RESULTS. At present, 120 subjects have been enrolled (35 cases, 85 controls), with interim data available for 51 subjects (12 cases, 39 controls). Striking genetic susceptibility of the general population is observed, with the IL-1B-5 llT prevalence of 97% (95% CI, 92-100%) in the controls. Heterozygote and homozygote frequencies are 62%(CT) and 36%(TT), respectively, unique in the world. Prevalence is similar in the cancer group. Endemic H. pylori infection is confirmed(86%). Analysis of DietHistory data reveals significant intake deficiencies noted among cancer patients with alphacarotene, lycopene, and selenium. CONCLUSIONS. Endemic gastric cancer genetic susceptibility(97%) is identified in the population of Westem Honduras, using population- based techniques. Analysts of population genetic susceptibility, bacterial virulence factors, and dietary cofactors is indicated. A region-appropriate gastric cancer screening program is warranted. $1185 Upper Gastrointestinal Tolerability of Once-weekly Alendronate 70 mg with Concomitant NSAID Use Anne De Papp, Joanne palmisano, Richard Petsuschke, Gregory Geba Safety assessments of oral bisphosphonates have focused on upper gastrointestinal (GI) adverse events (AEs), because of the known potential for bisphosphonates to imtate the upper GI mucosa. Similarly, nonsteroidal anti--inflammatory drugs (NSAIDs) may induce gastric mucosal damage, and are frequently used by the same patient population that is prescribed bisphosphonates. In order to determine the rate of clinical adverse G1 events with exposure to once--weekly alendronate 70 mg (ALN), and NSAIDs, we performed an analysis on a subgroup of 257 patients who received both medications concomitantly during a 12 week, randomized, placebo controlled osteoporosis trial. Survival analysis was performed using Kaplan Meier estimation, and significance was assessed using the log rank test. Logistic regression was used to assess the effect of treatment, NSA1D exposure and interaction on the rate of upper GI AEs. 450 women and men with osteoporosis, from 48 US sites were randomized to treatment with once--weekly ALN, or placebo (PBO) in a 1:1 ratio. 60.2% (135 of 224) of ALN patients, and 53.9% (122 of 226) of PBO patients, reported concomitant use of NSA1DS or aspirin during the study. In the analysis of upper Gl AEs of the all patients treated population, 25 ALN patients and 30 PBO patiems reported one or more upper GI AEs, (11% and 13% respectively; p= NS). In the subgroup of patients taking NSAIDs concomitantly, 15 ALN patients, and 14 PBO patients reported upper GI AEs (11.1% vs 11.6% respectively; p = NS). Logistic regression revealed no significant interaction between once--weekly ALN and concomitant NSA1D use. We conclude that once--weekly alendro- hate 70 mg, was generally well tolerated, and when used concomitantly with NSA1Ds, did not increase the rate of upper GI AEs relative to placebo over a 3 month study period. AGA Abstracts A-168

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Page 1: Endemic gastric cancer genetic susceptibility in Western Honduras

either NERD or mild erosive disease, but some may have underlying peptic ulcer disease or gastric cancer. ERD was associated with older age, male gender, higher body mass index, smoking, alcohol, and lower prevalence of minor psychiatric morbidity compared to NERD.

Sl181

Quality of Life in a General Adult Population with Gastroesophageal Reflux Symptoms and/or Esophagitis. A Report from the Kalixanda Study Pertti Aro, Jukka Ronkainen, Tom Storskrubb, Elisabeth Bolling-Sternevald, Tore Lind, Hans Graffner, Nicholas J. Talley, Lars Agreus

Background and Aims: It is well known that quality of life (QoL) is impaired in patients with symptomatic gastroesophageal reflux disease (GERD), but data are scarce for non- patients with GERD. For non-patients with esophagitis (E-it), no QoL data are available. The aim of this study was to determine QoL in a random sample of a Swedish adult population with or without esophagitis and GERD. Methods: A random sample (n = 3000, age 18-80 years, mean age 53.5, 51% women) of two northern Swedish municipalities (n=21 610) was surveyed using a validated GI symptom questionnaire. A random sample of 1001 of the responders (n=2122, 71%) completed an esophagogastroduodenoscopy (EGD), 362 (23%) declined and 203 (13%) had contraindications. GERD was defined as the presence of troublesome heartburn and/or acid regurgitation during the past three months. E-it was defined as any grade of Los Angeles A-D. QoL was evaluated with SF-36 with the domains Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Mental Health (MH), Vitality (VT), Social Functioning (SF) and Role-Emotional (RE). Results: EGD was performed and an evahiable SF-36 was obtained in 999 subjects (mean age 53.5 years, 51.3% women). GERD was reported by 399 and E-it was found in 151 subjects (Los Angeles A n = 106, B n = 3 8 , C n = 3 and D n = 2 subjects, missing data n = 2). 97 (64.2%) of those with E-it had GERD symptoms, while 54 had not. In univariate analysis of SF-36, those with GERD had significantly lower scores in all domains except RE (p=0.07) compared to those without (the 54 subjects with symptom free E-it excluded). The 151 subjects with E-it had a significantly lower score only in the GH domain (p =0.02) compared to the 848 without E-it. 36 of the 151 had used acid reducing drugs (ARD: antacids, H2-blockers or PPI) and they had significantly lower scores in all domains except for BP. When comparing symptomatic (n=97) to asymptomatic E-it (n=54), the former scored significantly lower in GH, VT and MH. Among those with GERD symptoms, no significant difference was shown in any SF-36 domain between those with and those without E-ti. When introducing also age, sex, BM1 and the use of ARD within the past three months into a logistic regression analysis model, GERD remained an independent worsening predictor for all SF-36 domains except RE, while esophagitis did not. Conclusions: GERD symptoms affect QoL in an adult non-patient population, while E-it per se does not.

$1182

Gastroesophageal Reflux Is More Prominent In Western Dyspeptics: A Prospective Comparison Study Of British and South East Asian Patients with Dyspepsia Sanjiv Mahadeva, Muthukarapan C. Raman, Mark Follows, Khean-Lee Goh, Anthony T. Axon, Paul Moayyedi

BACKGROUND There is a paucity of data directly comparing the incidence of gastro- esophageal reflux disease (GERD) in Western and Eastern populations. We therefore com- pared clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and Asia in a cross-sectional study. METHODS Patients with uncomplicated dyspepsia attending endoscopy units in both institu- tions were prospectively interviewed and underwent subsequent endoscopy from January 1999 to June 2001 (Leeds, UK) and between January and August 2002 (Knafa Lumpur, Malaysia). RESULTS 693 patients from Kuala Lumpur and 392 patients from Leeds of Caucasian race were included in the analysis. The mean age was 48.7 +- 15.8 and 47.5 _+ 13.8 years for the Malaysian and British patients respectively (p = NS). There was a higher proportion of cigarette smoking (39.5% vs 13.4%, p < 0.0001), alcohol consumption (32.5% vs 2.5%, p < 0.0001), NSAID use (33.2% vs 23.4%, p=0.005) and H. pylori infection (45.3% vs 23.5%, p < 0.001) amongst the British patients. GERD symptoms were more common in British compared to Malaysian patients (heartburn (66.2% vs 37.4%), regurgita- tion (60.1% vs 30.2%) and dysphagia (23.7% vs 6.7%) p < 0.0001). This correlated to an increased endoscopic finding of refhix oesophagitis (29.6% vs 5.8%) and Barrett's oesophagus (3.8% vs 0.7%) amongst British patients (p< 0.001). A logistic regression model revealed that Caucasian race (OR 9.1; 95% CI =4.2 to 20.1), male sex (OR 2.0; 95% CI= 1.2 to 3.2) and H. pylori infection (OR 0.4; 95% CI = 0.2 to 0.6) were independent predictors for reflux oesophagitis. Heartburn had a 75% sensitivity and 38% specificity for detecting oesophagitis in British patients compared to a 45% sensitivity and 63% specificity in Malaysian patients. CONCLUSIONS GERD is more predominant in Western patients and their symp- toms are more predictive of pathology compared to their South East Asian counterparts.

$1183

Ethnic Differences in Gastric Cancer in a Multiracial Asian Population: a Case- Control Study Khean-Lee Goh, Phaik-Leng Cheah, Md Noorfaridah, N. Parasakthi

Background: Some of the highest incidences of gastric cancer have been reported in Asia with rates in excess of 80 per 100,00 population. However marked differences exist between different geographical regions and between different ethnic groups in Asia. Malaysia epito- mizes the muhiraciality of the Asian population with three major Asian races: Malay, Chinese and Indian living together. Objectives: To determine risk factors, particularly, ethnicity for gastric cancer in Malaysian patients Methods: A prospective age and sex-matched hospital based case-control study was performed at the University of Malaya Medical Center, Kuala Lumpur. Consecutive patients presenting with gastric cancer were recruited and subjected to a detailed questionnaire and had sera taken for H.pylori serology. H.pylori serology was

performed using a locally validated serological test: HEL-p II test (AMRAD, Australia) which has been shown to have a high sensitivity and specificity. Controls were chosen from hospital patiems who did not have any gastric nor GIT diseases and were sex and age-matched in a ratio of 2:1. Comparisons between cases and comrols were made using X2 test. Multivariate analysis was performed using multiple logistic regression analysis. Results: Eighty-seven cases of gastric cancer and 174 controls were recruited for the study. The mean age of controls was 58.5 yrs and cases 61.4 yrs. Analysis of the prevalence of gastric cancer- Chinese vs Malay: p<0.001, odds ratio (OR) 13.6 (4.4,47.6) and vs Indian p<O.001 OR 5.5 (2.8,11.1). Following multiple logistic regression analysis, the following remained significant indepen- dent risk factors: Chinese race- OR 10.2 (2.9, 36.5), low education- 9.8 (2.0, 37.5), smoking- 2.5 (1.2, 5.1), low consumption of fresh fruits and vegetables- 6.6 (1.6, 28.2), frequent ingestion of salted foods- 5.2 (1.3, 20.0) and H.pylori infection- 2.5 (1.2, 5.6). Conclusions: The role of ethnicity in predicting gastric cancer in our multiracial population is interesting. Chinese race had a higher risk compared to the two other major races in the country: Malays and Indians.

$1184

Endemic Gastric Cancer Genetic Susceptibility in Western Honduras Douglas Morgan, Ricardo Dominguez, Temitope Keku, Paris Heidt, Darn McGinn

BACKROUND. Gastric cancer is the second leading cause of cancer mortality in the world with significant geographic variability, lnterleukin-lB genotypes (-511T, -31T, -RN*2) are associated in H. pylori infected patients in Europe and Asia. The backround prevalence of polymorphisms in these populations ranges 50-70% (-511T; CT, 39-50%; TT, 11-21%). A systematic evaluation of gastric cancer risk factors (genetic, bacterial, dietary) in a popufation- based design is lacking. METHODS. The current study is a prospective, population-based, case-control design in western Honduras, Central America. The western region of Honduras (half million population, 95% Hispanic mestizo) is identified as a high incidence region in a recent 10 year survey. The estimated standardized gastric cancer incidence rate for the year 2000 was 39 and 21 for males and females, respectively (per 100,000 world standard population). 25% and 12% of cases were less than ages of 50 and 35, respectively. In the current study, gastric cancer cases were enrolled in prospective fashion from the Western Regional Hospital. Satellite imagery from the Community Development Department facili- tated a population-based approach to comrol recruitment. Controls were balanced among the sexes and age ranges (18-34, 35-49, 50-64, >65). Genomic DNA was obtained from whole blood per protocol(Gentra Systems) H. pylori status was established by EL1SA. Gastric cancer cases were confirmed by histology. The image-based DietHistory was used to establish dietary and micronutrient intake. RESULTS. At present, 120 subjects have been enrolled (35 cases, 85 controls), with interim data available for 51 subjects (12 cases, 39 controls). Striking genetic susceptibility of the general population is observed, with the IL-1B-5 l lT prevalence of 97% (95% CI, 92-100%) in the controls. Heterozygote and homozygote frequencies are 62%(CT) and 36%(TT), respectively, unique in the world. Prevalence is similar in the cancer group. Endemic H. pylori infection is confirmed(86%). Analysis of DietHistory data reveals significant intake deficiencies noted among cancer patients with alphacarotene, lycopene, and selenium. CONCLUSIONS. Endemic gastric cancer genetic susceptibility(97%) is identified in the population of Westem Honduras, using population- based techniques. Analysts of population genetic susceptibility, bacterial virulence factors, and dietary cofactors is indicated. A region-appropriate gastric cancer screening program is warranted.

$1185

Upper Gastrointestinal Tolerability of Once-weekly Alendronate 70 mg with Concomitant NSAID Use Anne De Papp, Joanne palmisano, Richard Petsuschke, Gregory Geba

Safety assessments of oral bisphosphonates have focused on upper gastrointestinal (GI) adverse events (AEs), because of the known potential for bisphosphonates to imtate the upper GI mucosa. Similarly, nonsteroidal anti--inflammatory drugs (NSAIDs) may induce gastric mucosal damage, and are frequently used by the same patient population that is prescribed bisphosphonates. In order to determine the rate of clinical adverse G1 events with exposure to once--weekly alendronate 70 mg (ALN), and NSAIDs, we performed an analysis on a subgroup of 257 patients who received both medications concomitantly during a 12 week, randomized, placebo controlled osteoporosis trial. Survival analysis was performed using Kaplan Meier estimation, and significance was assessed using the log rank test. Logistic regression was used to assess the effect of treatment, NSA1D exposure and interaction on the rate of upper GI AEs. 450 women and men with osteoporosis, from 48 US sites were randomized to treatment with once--weekly ALN, or placebo (PBO) in a 1:1 ratio. 60.2% (135 of 224) of ALN patients, and 53.9% (122 of 226) of PBO patients, reported concomitant use of NSA1DS or aspirin during the study. In the analysis of upper Gl AEs of the all patients treated population, 25 ALN patients and 30 PBO patiems reported one or more upper GI AEs, (11% and 13% respectively; p = NS). In the subgroup of patients taking NSAIDs concomitantly, 15 ALN patients, and 14 PBO patients reported upper GI AEs (11.1% vs 11.6% respectively; p = NS). Logistic regression revealed no significant interaction between once--weekly ALN and concomitant NSA1D use. We conclude that once--weekly alendro- hate 70 mg, was generally well tolerated, and when used concomitantly with NSA1Ds, did not increase the rate of upper GI AEs relative to placebo over a 3 month study period.

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