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Dietary factors affecting the prevalence of distal colorectal adenomas and metaplastic polyps
April 2000
AGAA757
gene product overexpression. Findings: The majority of Egyptian tumors was located in the rectum (51%, p=0.OO6 to <0.0001 vs. western groups), and was poorly differentiated (59%). Mucinous carcinoma was common (37%). Tumors with high levels of MSI (MSI-H) were frequent (37%), but K-ras mutation was uncommon (13%,p=0.07 to 0.001). High rates of MSI-H in rectal cancer (36%,p=0.07 to <0.0001) and of p53 overexpression in MSI-H tumors (50%,p<0.0001) were found, but MSI-H in young Egyptians under 40 were rare (8%). The profile of phenotypic and genotypic characteristics of Egyptian tumors differed from all three western compaison groups. Cluster analysis identified three subsets of Egyptian patients.young patients with microsatellite-stable poorly differentiated colorectal carcinoma; older patients with rnicrosatellite-stable well-or moderately differentiated carcinoma; and older patients with MSI-H carcinomas. Interpretation: The molecular pathology of Egyptian colorectal cancer shows unique differences from western patients. Studies on gene-environment interaction may offer an opportunity to explain the three evident pathogenetic clusters. 4076 DIETARY FACTORS AFFECTING THE PREVALENCE OF DISTAL COLORECTAL ADENOMAS AND METAPLASTIC POLYPS. Mark A. Watson, Rob Edwards, Tom Cecil, Chris Macklin, Sheila Bingham, Wendy Atkin, Dept of Surg, N +N Hosp, Norwich, United Kingdom; Icrf, London, United Kingdom; Dept of Surg, QAH, Portsamouth, United Kingdom; Dept of Surg, LGH, Leeds, United Kingdom; MRC Dunn Human Nutrition Unit, Cambridge, United Kingdom; ICRF Colorectal Cancer Unit, London, United Kingdom. INTRODUCTION When compared with colorectal cancer, relatively little is known regarding the effect of diet on the development of colorectal adenomatous and metaplastic polyps. Dietary assessments in case-control studies are subject to bias as dietary recall may be modified by the development of symptoms and knowledge of the diagnosis. We have assessed dietary intake in 10,906 asymptomatic volunteers prior to a screening flexible sigmoidoscopy in four regions of the UK (Norwich, Leeds, Portsmouth, Harrow). METHODS People aged 55-64 years attending for a screening flexible sigmoidoscopy as part of a trial completed a food frequency questionnaire prior to their test. Those investigated for lower GI symptoms during the previous 2 years or with a history of colitis or colorectal neoplasia were excluded. Food frequency was divided into nine categories and compared in cases and polyp free controls. Odds ratios are adjusted for sex. CONCLUSION These data support those in the literature for risk factors for adenomas, which also appear to be important for metaplastic polyps.
4078 THE SIZE OF COLORECTAL ADENOMAS AS A RISK FACTOR FOR COLORECTAL CANCERS. Yutaka Yamaji, Makoto Okamoto, Haruhiko Yoshida, Takao Kawabe, Yasushi Shiratori, Hitoshi Ikuma, Keiji Saito, Keiji Yokouchi, Toru Mitsushima, Masao Ornata, Univ of Tokyo, Tokyo, Japan; Kameda Gen Hosp, Chiba, Japan. [Introduction] Colorectal adenomas are claimed to be precancerous lesions which develop colorectal cancers on the basis of the adenoma-carcinoma sequence. However, colorectal adenomas are much more common lesions than colorectal cancers and tiny colorectal adenomas are frequently discovered particulaly by vigorous colonoscopy. We evaluated the size of colorectal adenomas as a risk factor for colorectal cancers. Methods: We conducted 59,324 of total colonoscopy to 22,277 Japanese during our annual medical health check-up since 1983 until 1998. The subjects had not been screened neither by their symptoms nor by fecal occult blood tests, and undertook colonoscopy as the first-choice exanination to check their colorectal lesions. At each examination, all of the polyps ::=:5mm and the lesions <5mm suspected of neoplasia were resected. All the subjects were encouraged to undertake annually repeated follow-up examination by total colonoscopy irrespective of the results of the previous examinations. The following respects were investigated on the basis of all the neoplastic lesions we found according to size : 1) the ratio between malignant (including carcinoma in situ and invasive carcinoma) and benign neoplastic lesions, 2) the incidence of colorectal cancers after adenomas were endoscopically resected, 3) the incidence of colorectal adenomas after adenomas were resected. Results: 1) A total of 13,549 neoplastic lesions were found. Among them, 8,397 were <5mm (malignant = 3, 0.04%), 4,070 were 5-9mm (malignant = 32, 0.8%), and 1,082 were ::=:lOmm (malignant = 192, 18%).2) Out of 9,461 subjects who had no neoplastic lesions found at the first examination, 32 subjects (0.3%) developed newly colorectal cancers during the follow-up examinations. On the other hand, 2 out of 1,062 subjects (0.2%) who had only adenomas <5mm, 7 out of 786 subjects (0.9%) who had adenomas 5-9mm at most, and 4 out of 298 subjects (1.3%) who had adenomas ::=:lOmm developed colorectal cancers. 3) At the first examination, 3,853 out of 22,277 subjects (17.3%) had adenomas. And then, 2,463 «5mm 1,668, 5-9mm 687, ::=:IOmm 108) out of 9,461 subjects (26.0%) without any neoplastic lesions developed newly adenomas. Conclusion: The risk for colorectal cancers both in the present and in the future increased according to the size of colorectal adenomas. However, adenomas <5mm seemed to have only a negligible risk.
4079 Results
Adenomas OR 95%CI
Metaplastic 95%CI OR
Vegetables(total) Brown bread Whitebread Meat Beef Pork Lamb Chicken Bacon Spam, processed meats Sausages Fish
0.96 0.96 1.03 1.03 1.07 1.10 1.08 0.95 1.05 1.08 1.11 098
0.94 0.95 1.05 1.06 1.08 1.07 1.04 0.98 1.06 1.12 1.12 094
0.93,1.00 0.93,0.99 1.00,1.07 0.99,1.09 1.02,1.13 1.04,1.16 1.01,1.14 0.89,1.01 1.00,1.10 1.02,1.14 1.04,1.18 0.92,1.04
0.90,0.98 0.93,0.98 1.02,1.08 1.00,1.11 1.03,1.14 1.01,1.13 0.98,1.10 0.92,1.04 1.00,1.12 1.06,1.18 1.05,1.19 0.88,1.00
4077 ESTROGEN RECEPTOR BETA (ER-B) IS EXPRESSED IN HUMAN COLORECTAL ADENOCARCINOMAS. Deborah Witte, Najeeba Ali, Nicole Carlson, Mamoun Younes, Baylor Coli of Medicine, Houston, TX. It has been recently reported that colon cancer cell lines express functional estrogen receptor beta (ER-B), but not the classical estrogen receptor alpha (ER-A). The aim of this study was to determine whether ER-B is expressed in human colon cancer tissues. Six samples from 6 colorectal carcinomas were subjected to western blot analysis using a polyclonal antibody raised against a synthetic peptide corresponding to the NH2 terminus of human ER-B. The same antibody was also used to immunohistochemically stain sections of formalin-fixed and paraffin-embedded tissue from 41 colorectal carcinomas using standard imrnunoperoxidase method. A subset of the tumors was also immunohistochemically stained for ER-A using a commercially available monoclonal antibody. The human breast cancer cell line MCF-7, known to express both ER-A and ER-B was used as positive control. Four (67%) of the 6 carcinomas showed bands corresponding to ER-B by western blot analysis, and 26 (63%) of the 41 tumors investigated by immunohistochemistry were positive for ER-B. Typically, ER-B immunoreactivity was weak to moderate, occasionally strong, and present both in the nuclei and cytoplasm. Immunoreactivirty for the classical ER-A was not detected in any of the tumors examined. We conclude that a significant number of colorectal adenocarcinomas express ER-B. Whether colorectal carcinomas respond to treatment with antiestrogens should be investigated.
CLINICOPATHOLOGICAL DIFFERENCES BETWEEN METACHRONOUS AND SYNCHRONOUS MULTIPLE COLORECTAL CARCINOMAS. Takayuki Yoshino, Shigeharu Kato, Yasushi Sano, Ikurou Koba, Fumio Nagashima, Jun Arao, Kiyomi Mera, Kuang I. Fu, Narikazu Boku, Atsushi Ohtsu, Shigeaki Yoshida, Takahiro Fujii, National Cancer Ctr Hosp East, Kashiwa, Japan; National Cancer Ctr Hosp, Tokyo, Japan. Background: Multiple colorectal carcinomas (MCRC) have been reported to associate colorectal adenomas and extracolonic malignancies. Many authors have reported that flat or depressed type colorectal cancers may have a different pathway from the adenoma-carcinoma sequence, that is, de novo cancer, especially in the right colon. Few studies have been reported about clinicopathological differences between synchronous MCRC (SMCRC) and metachronous MCRC (M-MCRC). Aim: To clarify the clinicopathological differences between S-MCRC and M-MCRC. Methods: The subjects consisted of 93 patients, with 216 colorectal carcinomas, and 60 coexistent adenomas defined as more than 6 mm in diameter andJor high grade dysplasia histologically, at the National Cancer Center Hospital East, Japan, from July 1992 to June 1998. Macroscopically, Intramucosal and submucosal invasive cancers (early cancers), and adenomas were classified into three groups; protruded, flat and depressed types. We investigated the clinicopathological differences (location, morphology, extracolonic malignancies, adenomas) between S-MCRC and M-MCRC. Results: Sixty-two patients with S-MCRC have 137 cancers (advanced: 39, early: 98) and 30 adenomas, whereas 31 patients with M-MCRC have 79 cancers (advanced: 20, early: 59) and 30 adenomas. S-MCRCIM-MCRC were 33 (24.1%)/31 (39.7%) in the right colon, 65 (47.4%)/34 (43.6%) in the left, 39 (28.5%)/14 (17.9%) in the rectum, respectively. The ratio of flat/depressed to protruded type in early cancers were significantly higher in the MMCRC (0.73, 22/30, p=0.02) than S-MCRC (0.26, 20/77, p=0.005). The coincidence of extracolonic malignancies was significantly higher in MMCRC than S-MCRC (25.8%, 8/31 vs 6.5%, 4/62, p=O.Ol). Adenomas with S-MCRCIM-MCRC were 14 (46.7%)/19 (63.4%) in the right colon, 12 (40.0%)/10 (33.3%) in the left, 4 (13.3%)/1 (3.3%) in the rectum, respectively. The ratio of flat/depressed to protruded type adenomas was not significant between those in S-MCRC (0.66, 12118) and M-MCRC (0.58, 11/19). Conclusion: Our results indicate that some M-MCRC may be implicated in different carcinogenesis from adenoma-carcinoma sequence.
AGAA757
gene product overexpression. Findings: The majority of Egyptian tumors was located in the rectum (51%, p=0.OO6 to <0.0001 vs. western groups), and was poorly differentiated (59%). Mucinous carcinoma was common (37%). Tumors with high levels of MSI (MSI-H) were frequent (37%), but K-ras mutation was uncommon (13%,p=0.07 to 0.001). High rates of MSI-H in rectal cancer (36%,p=0.07 to <0.0001) and of p53 overexpression in MSI-H tumors (50%,p<0.0001) were found, but MSI-H in young Egyptians under 40 were rare (8%). The profile of phenotypic and genotypic characteristics of Egyptian tumors differed from all three western compaison groups. Cluster analysis identified three subsets of Egyptian patients.young patients with microsatellite-stable poorly differentiated colorectal carcinoma; older patients with rnicrosatellite-stable well-or moderately differentiated carcinoma; and older patients with MSI-H carcinomas. Interpretation: The molecular pathology of Egyptian colorectal cancer shows unique differences from western patients. Studies on gene-environment interaction may offer an opportunity to explain the three evident pathogenetic clusters. 4076 DIETARY FACTORS AFFECTING THE PREVALENCE OF DISTAL COLORECTAL ADENOMAS AND METAPLASTIC POLYPS. Mark A. Watson, Rob Edwards, Tom Cecil, Chris Macklin, Sheila Bingham, Wendy Atkin, Dept of Surg, N +N Hosp, Norwich, United Kingdom; Icrf, London, United Kingdom; Dept of Surg, QAH, Portsamouth, United Kingdom; Dept of Surg, LGH, Leeds, United Kingdom; MRC Dunn Human Nutrition Unit, Cambridge, United Kingdom; ICRF Colorectal Cancer Unit, London, United Kingdom. INTRODUCTION When compared with colorectal cancer, relatively little is known regarding the effect of diet on the development of colorectal adenomatous and metaplastic polyps. Dietary assessments in case-control studies are subject to bias as dietary recall may be modified by the development of symptoms and knowledge of the diagnosis. We have assessed dietary intake in 10,906 asymptomatic volunteers prior to a screening flexible sigmoidoscopy in four regions of the UK (Norwich, Leeds, Portsmouth, Harrow). METHODS People aged 55-64 years attending for a screening flexible sigmoidoscopy as part of a trial completed a food frequency questionnaire prior to their test. Those investigated for lower GI symptoms during the previous 2 years or with a history of colitis or colorectal neoplasia were excluded. Food frequency was divided into nine categories and compared in cases and polyp free controls. Odds ratios are adjusted for sex. CONCLUSION These data support those in the literature for risk factors for adenomas, which also appear to be important for metaplastic polyps.
4078 THE SIZE OF COLORECTAL ADENOMAS AS A RISK FACTOR FOR COLORECTAL CANCERS. Yutaka Yamaji, Makoto Okamoto, Haruhiko Yoshida, Takao Kawabe, Yasushi Shiratori, Hitoshi Ikuma, Keiji Saito, Keiji Yokouchi, Toru Mitsushima, Masao Ornata, Univ of Tokyo, Tokyo, Japan; Kameda Gen Hosp, Chiba, Japan. [Introduction] Colorectal adenomas are claimed to be precancerous lesions which develop colorectal cancers on the basis of the adenoma-carcinoma sequence. However, colorectal adenomas are much more common lesions than colorectal cancers and tiny colorectal adenomas are frequently discovered particulaly by vigorous colonoscopy. We evaluated the size of colorectal adenomas as a risk factor for colorectal cancers. Methods: We conducted 59,324 of total colonoscopy to 22,277 Japanese during our annual medical health check-up since 1983 until 1998. The subjects had not been screened neither by their symptoms nor by fecal occult blood tests, and undertook colonoscopy as the first-choice exanination to check their colorectal lesions. At each examination, all of the polyps ::=:5mm and the lesions <5mm suspected of neoplasia were resected. All the subjects were encouraged to undertake annually repeated follow-up examination by total colonoscopy irrespective of the results of the previous examinations. The following respects were investigated on the basis of all the neoplastic lesions we found according to size : 1) the ratio between malignant (including carcinoma in situ and invasive carcinoma) and benign neoplastic lesions, 2) the incidence of colorectal cancers after adenomas were endoscopically resected, 3) the incidence of colorectal adenomas after adenomas were resected. Results: 1) A total of 13,549 neoplastic lesions were found. Among them, 8,397 were <5mm (malignant = 3, 0.04%), 4,070 were 5-9mm (malignant = 32, 0.8%), and 1,082 were ::=:lOmm (malignant = 192, 18%).2) Out of 9,461 subjects who had no neoplastic lesions found at the first examination, 32 subjects (0.3%) developed newly colorectal cancers during the follow-up examinations. On the other hand, 2 out of 1,062 subjects (0.2%) who had only adenomas <5mm, 7 out of 786 subjects (0.9%) who had adenomas 5-9mm at most, and 4 out of 298 subjects (1.3%) who had adenomas ::=:lOmm developed colorectal cancers. 3) At the first examination, 3,853 out of 22,277 subjects (17.3%) had adenomas. And then, 2,463 «5mm 1,668, 5-9mm 687, ::=:IOmm 108) out of 9,461 subjects (26.0%) without any neoplastic lesions developed newly adenomas. Conclusion: The risk for colorectal cancers both in the present and in the future increased according to the size of colorectal adenomas. However, adenomas <5mm seemed to have only a negligible risk.
4079 Results
Adenomas OR 95%CI
Metaplastic 95%CI OR
Vegetables(total) Brown bread Whitebread Meat Beef Pork Lamb Chicken Bacon Spam, processed meats Sausages Fish
0.96 0.96 1.03 1.03 1.07 1.10 1.08 0.95 1.05 1.08 1.11 098
0.94 0.95 1.05 1.06 1.08 1.07 1.04 0.98 1.06 1.12 1.12 094
0.93,1.00 0.93,0.99 1.00,1.07 0.99,1.09 1.02,1.13 1.04,1.16 1.01,1.14 0.89,1.01 1.00,1.10 1.02,1.14 1.04,1.18 0.92,1.04
0.90,0.98 0.93,0.98 1.02,1.08 1.00,1.11 1.03,1.14 1.01,1.13 0.98,1.10 0.92,1.04 1.00,1.12 1.06,1.18 1.05,1.19 0.88,1.00
4077 ESTROGEN RECEPTOR BETA (ER-B) IS EXPRESSED IN HUMAN COLORECTAL ADENOCARCINOMAS. Deborah Witte, Najeeba Ali, Nicole Carlson, Mamoun Younes, Baylor Coli of Medicine, Houston, TX. It has been recently reported that colon cancer cell lines express functional estrogen receptor beta (ER-B), but not the classical estrogen receptor alpha (ER-A). The aim of this study was to determine whether ER-B is expressed in human colon cancer tissues. Six samples from 6 colorectal carcinomas were subjected to western blot analysis using a polyclonal antibody raised against a synthetic peptide corresponding to the NH2 terminus of human ER-B. The same antibody was also used to immunohistochemically stain sections of formalin-fixed and paraffin-embedded tissue from 41 colorectal carcinomas using standard imrnunoperoxidase method. A subset of the tumors was also immunohistochemically stained for ER-A using a commercially available monoclonal antibody. The human breast cancer cell line MCF-7, known to express both ER-A and ER-B was used as positive control. Four (67%) of the 6 carcinomas showed bands corresponding to ER-B by western blot analysis, and 26 (63%) of the 41 tumors investigated by immunohistochemistry were positive for ER-B. Typically, ER-B immunoreactivity was weak to moderate, occasionally strong, and present both in the nuclei and cytoplasm. Immunoreactivirty for the classical ER-A was not detected in any of the tumors examined. We conclude that a significant number of colorectal adenocarcinomas express ER-B. Whether colorectal carcinomas respond to treatment with antiestrogens should be investigated.
CLINICOPATHOLOGICAL DIFFERENCES BETWEEN METACHRONOUS AND SYNCHRONOUS MULTIPLE COLORECTAL CARCINOMAS. Takayuki Yoshino, Shigeharu Kato, Yasushi Sano, Ikurou Koba, Fumio Nagashima, Jun Arao, Kiyomi Mera, Kuang I. Fu, Narikazu Boku, Atsushi Ohtsu, Shigeaki Yoshida, Takahiro Fujii, National Cancer Ctr Hosp East, Kashiwa, Japan; National Cancer Ctr Hosp, Tokyo, Japan. Background: Multiple colorectal carcinomas (MCRC) have been reported to associate colorectal adenomas and extracolonic malignancies. Many authors have reported that flat or depressed type colorectal cancers may have a different pathway from the adenoma-carcinoma sequence, that is, de novo cancer, especially in the right colon. Few studies have been reported about clinicopathological differences between synchronous MCRC (SMCRC) and metachronous MCRC (M-MCRC). Aim: To clarify the clinicopathological differences between S-MCRC and M-MCRC. Methods: The subjects consisted of 93 patients, with 216 colorectal carcinomas, and 60 coexistent adenomas defined as more than 6 mm in diameter andJor high grade dysplasia histologically, at the National Cancer Center Hospital East, Japan, from July 1992 to June 1998. Macroscopically, Intramucosal and submucosal invasive cancers (early cancers), and adenomas were classified into three groups; protruded, flat and depressed types. We investigated the clinicopathological differences (location, morphology, extracolonic malignancies, adenomas) between S-MCRC and M-MCRC. Results: Sixty-two patients with S-MCRC have 137 cancers (advanced: 39, early: 98) and 30 adenomas, whereas 31 patients with M-MCRC have 79 cancers (advanced: 20, early: 59) and 30 adenomas. S-MCRCIM-MCRC were 33 (24.1%)/31 (39.7%) in the right colon, 65 (47.4%)/34 (43.6%) in the left, 39 (28.5%)/14 (17.9%) in the rectum, respectively. The ratio of flat/depressed to protruded type in early cancers were significantly higher in the MMCRC (0.73, 22/30, p=0.02) than S-MCRC (0.26, 20/77, p=0.005). The coincidence of extracolonic malignancies was significantly higher in MMCRC than S-MCRC (25.8%, 8/31 vs 6.5%, 4/62, p=O.Ol). Adenomas with S-MCRCIM-MCRC were 14 (46.7%)/19 (63.4%) in the right colon, 12 (40.0%)/10 (33.3%) in the left, 4 (13.3%)/1 (3.3%) in the rectum, respectively. The ratio of flat/depressed to protruded type adenomas was not significant between those in S-MCRC (0.66, 12118) and M-MCRC (0.58, 11/19). Conclusion: Our results indicate that some M-MCRC may be implicated in different carcinogenesis from adenoma-carcinoma sequence.