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The Effect of Obesity on Esophageal Adenocarcinoma
validated questionnaire. RESULTS: We found that increased age, male sex, decreased physical activity and increased height were independently associated with adenoma prevalence. For each 10 year increase in age, the odds of having an adenoma increased by 1.5 (95% CI 1.21.9). The odds ratio for males compared to females was 1.6 (95% CI 1.2-2.2). Compared to patients in the upper tertile, patients in the lowest tertile of physical activity had an odds ratio of 1.5 (95%CI 1.2-2.2). For every 6-inch increase in height the OR increased by 1.2 (95%CI 1.1-1.4). After adjusting for these variables, waist-hip ratio and BMI were associated with adenoma prevalence while percent body fat was not. Using the lowest tertile as the referent, patients in the upper tertile of waist-hip ratio had an OR of 2.0 (95%CI 1.2-3.2). Compared to patients with BMI < 25, obese patients (BMI>30) had an OR of 1.6 (95% CI 1.1-2.5). Percent body fat as measured by BIA was not associated with adenoma status. Comparing the highest to lowest tertiles the OR was 1.0 (95% CI 0.7-1.6). CONCLUSIONS: Contrary to expectation, we found that percent body fat measured by BIA was not associated with adenoma prevalence while waist hip ratio and BMI were associated. The distribution of adipose tissue may be an important risk factor to be assessed by methods other than bioelectrical impedance.
The Effect of Obesity on Esophageal Adenocarcinoma Kevin J. Nattinger, Chung Yin Kong, Tristan J. Hayeck, Zehra Omer, Caihua Liang, Y. Claire Wang, Stuart J. Spechler, Pamela M. McMahon, G. Scott Gazelle, Chin Hur Background: Over the last 40 years, obesity has risen at an astonishing rate in the US, nearly tripling between 1973 and 2005. The incidence of esophageal adenocarcinoma (EAC) has undergone an even sharper increase over the same time period, growing by a factor of five. Epidemiologic studies have shown that many precursors of EAC, such as Barrett's esophagus (BE), are associated with obesity, leading some to suggest that obesity may be a contributing factor in the development of EAC. The trends in EAC and obesity do not, however, show the time lag that one would expect if obesity were a significant causal factor in EAC development. The aim of our study was to determine the extent to which the rise in obesity has affected the EAC incidence between 1973 and 2005. Methods: A previously validated computer simulation model of EAC (EACMo) was adapted for this analysis. The model was used to simulate two groups in the US white male population, OBESE (BMI above 30) and NON-OBESE (BMI below 30). The study period extended from 1973 to 2005, corresponding to the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) data. The model simulations were analyzed in two different scenarios. Scenario 1 depicted a hypothetical US population where the rates of obesity prevalence and progression to cancer did not change over the study period. Scenario 2 incorporated the rise in obesity prevalence over the same time period. Comparing the results of the two scenarios with each other and with SEER data provided an estimate of the number of EAC cases attributable to obesity. As a sensitivity analysis, we determined the odds ratio of EAC incidence associated with obesity necessary for Scenario 2 results to match SEER data. Results: The EAC incidence from each scenario as well as SEER data for each year simulated may be seen in Fig. 1, with representative points seen in Table 1. Scenario 1 resulted in 30,559 EAC cases in the US over the study period and 1,150 cases in 2005, while Scenario 2 resulted in 35,773 cases cumulatively and 1,607 in 2005. SEER incidence has 111,223 cases cumulatively and 7,173 cases in 2005, meaning that obesity accounted for 6.46% of EAC cases in the US between 1973 and 2005, and 7.59% of cases in 2005. The sensitivity analysis showed that an OR of 74 best matched the SEER incidence over the study period and 82 best matched the EAC incidence in 2005. Conclusions: The low percentage of EAC cases attributable to obesity supports the idea that obesity is unlikely to be a primary cause of the exponential rise in EAC incidence. The high ORs—between 27 and 30 times that reported in literature— required to recreate the historical SEER data by changing obesity alone further illustrates this notion. Table 1: EAC Incidence (per 100,000)
Sa1966 Influence of Gender on Peripheral Ghrelin Secretion. -Examination in the Aging MiceShunsuke Ohnishi, Hiroshi Takeda, Shuichi Muto, Koji Nakagawa, Chiharu Sadakane, Yayoi Saegusa, Miwa Nahata, Tomohisa Hattori, Masahiro Asaka Background/Aim: It is well known that ghrelin is an endogenous ligand that has been isolated and identified in the rat stomach; it is a hormone with powerful orexigenic effect. Although the concentration of peripheral ghrelin is known to show a differing dynamic in males and females, there are no studies regarding ghrelin variations in advanced-age males and females. In the present study, we investigated the differences between advanced-age male and female mice with regard to peripheral ghrelin secretion, and analyzed the mechanisms involved therein. Methods: We performed the tests using C57BL/6J mice aged 79-80 weeks (advanced-age mice) and 6 weeks (young mice). We collected their blood, hypothalamus, and stomach during fasting and feeding status to determine the ghrelin concentration and the expression of appetite-related genes. Results: Although the food intake in male mice over 6 h was lower in the advanced-aged mice, no difference was noted in advancedage female mice in comparison with the young-mice group. In advanced-age male mice, the rise in plasma acyl ghrelin level, as seen in young mice when fasting, was not observed. Contrary to this, in comparison with young mice, advanced-age female mice showed high plasma acyl ghrelin levels both when fasting and when feeding. The expression of the stomach preproghrelin gene was significantly increased in both males and females of the advanced-age group, and the expression of the gastric ghrelin acyl-modifying enzyme gene also showed an increasing trend. The expression of NPY/AgRP genes, which are hypothalamic orexigenic substances, decreased significantly in males with advancing age, while in advancedage female mice, NPY/AgRP gene expression showed an increasing trend. Furthermore, the expression of the POMC gene was significantly decreased. Conclusion: In male mice in comparison with female mice, a drop in the amount of food intake occurs as their age advances. On the other hand, the sustained food intake by female mice is probably related to the excessive secretion of plasma acyl ghrelin, which is not dependent on fasting or feeding.
Figure Plasma concentration of ghrelin in male and female aged mice. Sa1967 The Molecular Interaction of HSP20/HSP27/Cav-1 Modulating Contraction/ Relaxation is Affected During Aging Jean-Marc Fontaine, Sita Somara, Khalil N. Bitar
Figure 1: Annual EAC incidence over the study period
Background: The small heat shock proteins (sHSPs), HSP20, HSP27 and caveolin-1 have been shown to be involved in the regulation of the relaxation/contraction events. Colonic smooth muscle cells (CSMC) from aged animals exhibit reduced contraction which was reinstated to normal physiological levels by ectopic expression of caveolin-1, the main structural component of caveolae. Caveolin-1/HSP27 and HSP20/ HSP27 are known to interact. HSP20 can modulate caveolin-1/HSP27 interaction, however the regulation of this interaction in contraction and relaxation during aging is not known. Hypothesis: The role of HSP20, HSP27 and caveolin-1 during contraction/relaxation is affected during aging. Method: Colon smooth muscle cells were isolated from rat or rabbit. CFP-sHSP, CIT-sHSP or YFP-sHSP fusion protein expression vectors were used for these experiments. CSMC were transfected with vector DNA using Lipofectamine 2000. Forty eight hours later, the live cells were analyzed by quantitative Fluorescence Energy Transfer (qFRET) method to quantify the protein interactions. As an independent method Co-IP was also used to check protein interactions. Results: The data indicate that: (i) Interaction between HSP20 and HSP27 decreased (12%) when phosphomimic HSP27 (3D) was used suggesting that the phosphorylation state of HSP27 was important for the interaction of HSP20 with HSP27, (ii) The interaction between Cav-1/HSP27 and HSP20/HSP27 significantly decreased (40%, 8% respectively) in CSMC from aged rats compared to the interaction in CSMC from adult rats. (iii) Acetylcholine-induced interaction (Co-IP) of Caveolin-1 with HSP27 significantly
Sa1965 Percent Body Fat Measured by Bioelectrical Impedance is Not Associated With Colorectal Adenoma Status David J. Frantz, Joseph A. Galanko, Robert S. Sandler BACKGROUND: Obesity has been repeatedly shown to be a risk factor for colorectal neoplasia. The mechanism may be attributable to cytokines or hormonal changes resulting from insulin resistance. Bioelectrical impedance (BIA) is a novel method to assess fat body mass in the clinic. BIA could be a better measure of adiposity and adenoma risk, but this has not been previously tested. We conducted a large colonoscopy based cross-sectional study to evaluate BIA and other measures of obesity as risk factors for adenomas. METHODS: Study subjects were part of a large, cross-sectional study. Patients underwent colonoscopy at the University of North Carolina during a 24 month period starting in 2006. There were 255 patients with adenomas and 679 adenoma-free controls eligible for analysis. Anthropometric measures included height, weight, and waist-hip circumference. Percent body fat was measured using bioelectrical impedance with a TANITA Body Composition Analyzer TBF-300. Physical activity and other risk factors were assessed using a previously
S-357
AGA Abstracts
AGA Abstracts
Sa1964
The Effect of Obesity on Esophageal Adenocarcinoma Kevin J. Nattinger, Chung Yin Kong, Tristan J. Hayeck, Zehra Omer, Caihua Liang, Y. Claire Wang, Stuart J. Spechler, Pamela M. McMahon, G. Scott Gazelle, Chin Hur Background: Over the last 40 years, obesity has risen at an astonishing rate in the US, nearly tripling between 1973 and 2005. The incidence of esophageal adenocarcinoma (EAC) has undergone an even sharper increase over the same time period, growing by a factor of five. Epidemiologic studies have shown that many precursors of EAC, such as Barrett's esophagus (BE), are associated with obesity, leading some to suggest that obesity may be a contributing factor in the development of EAC. The trends in EAC and obesity do not, however, show the time lag that one would expect if obesity were a significant causal factor in EAC development. The aim of our study was to determine the extent to which the rise in obesity has affected the EAC incidence between 1973 and 2005. Methods: A previously validated computer simulation model of EAC (EACMo) was adapted for this analysis. The model was used to simulate two groups in the US white male population, OBESE (BMI above 30) and NON-OBESE (BMI below 30). The study period extended from 1973 to 2005, corresponding to the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) data. The model simulations were analyzed in two different scenarios. Scenario 1 depicted a hypothetical US population where the rates of obesity prevalence and progression to cancer did not change over the study period. Scenario 2 incorporated the rise in obesity prevalence over the same time period. Comparing the results of the two scenarios with each other and with SEER data provided an estimate of the number of EAC cases attributable to obesity. As a sensitivity analysis, we determined the odds ratio of EAC incidence associated with obesity necessary for Scenario 2 results to match SEER data. Results: The EAC incidence from each scenario as well as SEER data for each year simulated may be seen in Fig. 1, with representative points seen in Table 1. Scenario 1 resulted in 30,559 EAC cases in the US over the study period and 1,150 cases in 2005, while Scenario 2 resulted in 35,773 cases cumulatively and 1,607 in 2005. SEER incidence has 111,223 cases cumulatively and 7,173 cases in 2005, meaning that obesity accounted for 6.46% of EAC cases in the US between 1973 and 2005, and 7.59% of cases in 2005. The sensitivity analysis showed that an OR of 74 best matched the SEER incidence over the study period and 82 best matched the EAC incidence in 2005. Conclusions: The low percentage of EAC cases attributable to obesity supports the idea that obesity is unlikely to be a primary cause of the exponential rise in EAC incidence. The high ORs—between 27 and 30 times that reported in literature— required to recreate the historical SEER data by changing obesity alone further illustrates this notion. Table 1: EAC Incidence (per 100,000)
Sa1966 Influence of Gender on Peripheral Ghrelin Secretion. -Examination in the Aging MiceShunsuke Ohnishi, Hiroshi Takeda, Shuichi Muto, Koji Nakagawa, Chiharu Sadakane, Yayoi Saegusa, Miwa Nahata, Tomohisa Hattori, Masahiro Asaka Background/Aim: It is well known that ghrelin is an endogenous ligand that has been isolated and identified in the rat stomach; it is a hormone with powerful orexigenic effect. Although the concentration of peripheral ghrelin is known to show a differing dynamic in males and females, there are no studies regarding ghrelin variations in advanced-age males and females. In the present study, we investigated the differences between advanced-age male and female mice with regard to peripheral ghrelin secretion, and analyzed the mechanisms involved therein. Methods: We performed the tests using C57BL/6J mice aged 79-80 weeks (advanced-age mice) and 6 weeks (young mice). We collected their blood, hypothalamus, and stomach during fasting and feeding status to determine the ghrelin concentration and the expression of appetite-related genes. Results: Although the food intake in male mice over 6 h was lower in the advanced-aged mice, no difference was noted in advancedage female mice in comparison with the young-mice group. In advanced-age male mice, the rise in plasma acyl ghrelin level, as seen in young mice when fasting, was not observed. Contrary to this, in comparison with young mice, advanced-age female mice showed high plasma acyl ghrelin levels both when fasting and when feeding. The expression of the stomach preproghrelin gene was significantly increased in both males and females of the advanced-age group, and the expression of the gastric ghrelin acyl-modifying enzyme gene also showed an increasing trend. The expression of NPY/AgRP genes, which are hypothalamic orexigenic substances, decreased significantly in males with advancing age, while in advancedage female mice, NPY/AgRP gene expression showed an increasing trend. Furthermore, the expression of the POMC gene was significantly decreased. Conclusion: In male mice in comparison with female mice, a drop in the amount of food intake occurs as their age advances. On the other hand, the sustained food intake by female mice is probably related to the excessive secretion of plasma acyl ghrelin, which is not dependent on fasting or feeding.
Figure Plasma concentration of ghrelin in male and female aged mice. Sa1967 The Molecular Interaction of HSP20/HSP27/Cav-1 Modulating Contraction/ Relaxation is Affected During Aging Jean-Marc Fontaine, Sita Somara, Khalil N. Bitar
Figure 1: Annual EAC incidence over the study period
Background: The small heat shock proteins (sHSPs), HSP20, HSP27 and caveolin-1 have been shown to be involved in the regulation of the relaxation/contraction events. Colonic smooth muscle cells (CSMC) from aged animals exhibit reduced contraction which was reinstated to normal physiological levels by ectopic expression of caveolin-1, the main structural component of caveolae. Caveolin-1/HSP27 and HSP20/ HSP27 are known to interact. HSP20 can modulate caveolin-1/HSP27 interaction, however the regulation of this interaction in contraction and relaxation during aging is not known. Hypothesis: The role of HSP20, HSP27 and caveolin-1 during contraction/relaxation is affected during aging. Method: Colon smooth muscle cells were isolated from rat or rabbit. CFP-sHSP, CIT-sHSP or YFP-sHSP fusion protein expression vectors were used for these experiments. CSMC were transfected with vector DNA using Lipofectamine 2000. Forty eight hours later, the live cells were analyzed by quantitative Fluorescence Energy Transfer (qFRET) method to quantify the protein interactions. As an independent method Co-IP was also used to check protein interactions. Results: The data indicate that: (i) Interaction between HSP20 and HSP27 decreased (12%) when phosphomimic HSP27 (3D) was used suggesting that the phosphorylation state of HSP27 was important for the interaction of HSP20 with HSP27, (ii) The interaction between Cav-1/HSP27 and HSP20/HSP27 significantly decreased (40%, 8% respectively) in CSMC from aged rats compared to the interaction in CSMC from adult rats. (iii) Acetylcholine-induced interaction (Co-IP) of Caveolin-1 with HSP27 significantly
Sa1965 Percent Body Fat Measured by Bioelectrical Impedance is Not Associated With Colorectal Adenoma Status David J. Frantz, Joseph A. Galanko, Robert S. Sandler BACKGROUND: Obesity has been repeatedly shown to be a risk factor for colorectal neoplasia. The mechanism may be attributable to cytokines or hormonal changes resulting from insulin resistance. Bioelectrical impedance (BIA) is a novel method to assess fat body mass in the clinic. BIA could be a better measure of adiposity and adenoma risk, but this has not been previously tested. We conducted a large colonoscopy based cross-sectional study to evaluate BIA and other measures of obesity as risk factors for adenomas. METHODS: Study subjects were part of a large, cross-sectional study. Patients underwent colonoscopy at the University of North Carolina during a 24 month period starting in 2006. There were 255 patients with adenomas and 679 adenoma-free controls eligible for analysis. Anthropometric measures included height, weight, and waist-hip circumference. Percent body fat was measured using bioelectrical impedance with a TANITA Body Composition Analyzer TBF-300. Physical activity and other risk factors were assessed using a previously
S-357
AGA Abstracts
AGA Abstracts
Sa1964