AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were an...AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were analyzed between ESCC patients with(n = 766) and without(n = 1776) a family history of the cancer. The cases analyzed constituted all consecutive patients who had undergone cure-intent surgery at the Department of Thoracic Surgery of the 4th Hospital of Hebei Medical University from January 1 1975 to December 31 1989. Because we also originally aimed to examine the difference in survival time, only older subjects with a long follow-up period were selected.RESULTS: Overall, patients with ESCC and a positive family history of the cancer had a significantly younger age at onset and more multiple primary cancers than those without a positive family history(51.83 ± 8.39 vs 53.49 ± 8.23 years old, P = 0.000; 5.50% vs 1.70%, P = 0.000). Both of these differences were evident in subgroup analyses, however, no correlations were observed. While age at onset differed significantly by family history in males, smokers, and drinkers, the difference in multiple primary cancers by family history was significant in nonsmoking, nondrinking, and younger onset patients. In multivariate analysis, age over 50 years, tobacco smoking, and multiple primary cancers were found to be significant predictors of familial cancer: the corresponding OR(95%CI) and P-value were 0.974(0.963-0.985) and 0.000; 1.271(1.053-1.535) and 0.012; and 4.265(2.535-7.176) and 0.000, respectively.CONCLUSION: Patients with ESCC and a positive family history of the cancer had a significantly younger onset age and more multiple primary cancers than those without a positive family history. Sub-group analyses indicated that younger onset age may be due to the interaction of genetic predisposition and environmental hazards, and multiple primary cancers may only be due to genetic predisposition.展开更多
AIM:To investigate the epidemiological characteristics of colorectal cancer(CRC)in patients under 50 years of age across two institutions.METHODS:Records of patients under age 50 years of age who had CRC surgery over ...AIM:To investigate the epidemiological characteristics of colorectal cancer(CRC)in patients under 50 years of age across two institutions.METHODS:Records of patients under age 50 years of age who had CRC surgery over a 16 year period were assessed at two institutions.The following documents where reviewed:admission notes,operative notes,and discharge summaries.The main study variables included:age,presenting symptoms,family history,tumor location,operation,stage/differentiation of disease,and post operative complications.Stage of disease was classified according to the American Joint Committee on Cancer TNM staging system:tumor depth;node status;and metastases.RESULTS:CRC was found in 180 patients under age50 years(87 females,93 males;mean age 41.4±6.2years).Young patients accounted for 11.2%of cases during a 6 year period for which the full data set wasavailable.Eight percent had a 1stdegree and 12%a 2nd degree family CRC history.Almost all patients(94%)were symptomatic at diagnosis;common symptoms included:bleeding(59%),obstruction(9%),and abdominal/rectal pain(35%).Evaluation was often delayed and bleeding frequently attributed to hemorrhoids.Advanced stage CRC(Stage 3 or 4)was noted in 53%of patients.Most tumors were distal to the splenic flexure(77%)and 39%involved the rectum.Most patients(95%)had segmental resections;6 patients had subtotal/total colectomy.Poorly differentiated tumors were noted in 12%and mucinous lesions in 19%of patients of which most had Stage 3 or 4 disease.Twenty-two patients(13%)developed recurrence and/or progression of disease to date.Three patients(ages 42,42and 49 years)went on to develop metachronous primary colon cancers within 3 to 4 years of their initial resection.CONCLUSION:CRC was common in young patients with no family history.Young patients with symptoms merit a timely evaluation to avoid presentation with late stage CRC.展开更多
Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes （TSGs）. However, the mechanism...Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes （TSGs）. However, the mechanism of colorectal cancer （CRC） is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis. Methods Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity （LOH） mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients＇ tumor and normal DNA were analyzed via polymerase chain reaction （PCR） for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases. Results The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% （18/49） at D1S2622, and the lowest of 16.42% （11/67） at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data （patient sex, age, tumor size, growth pattern, or Dukes stage）. On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 （1q31.3-32.1） region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4展开更多
Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic an...Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC.During the past two decades,sporadic CRCs were classified into three major groups according to frequently altered/mutated genes.These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data.In the first half of this review,we describe the genetic pathways of sporadic CRCs and their clinicopathologic features.Recently,large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes.These infrequently mutated genes are likely described in a limited number of pathways.Gene-oriented models of CRC progression are being replaced by pathway-oriented models.In the second half of this review,we summarize the present knowledge of this research field and discuss its prospects.展开更多
文摘AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were analyzed between ESCC patients with(n = 766) and without(n = 1776) a family history of the cancer. The cases analyzed constituted all consecutive patients who had undergone cure-intent surgery at the Department of Thoracic Surgery of the 4th Hospital of Hebei Medical University from January 1 1975 to December 31 1989. Because we also originally aimed to examine the difference in survival time, only older subjects with a long follow-up period were selected.RESULTS: Overall, patients with ESCC and a positive family history of the cancer had a significantly younger age at onset and more multiple primary cancers than those without a positive family history(51.83 ± 8.39 vs 53.49 ± 8.23 years old, P = 0.000; 5.50% vs 1.70%, P = 0.000). Both of these differences were evident in subgroup analyses, however, no correlations were observed. While age at onset differed significantly by family history in males, smokers, and drinkers, the difference in multiple primary cancers by family history was significant in nonsmoking, nondrinking, and younger onset patients. In multivariate analysis, age over 50 years, tobacco smoking, and multiple primary cancers were found to be significant predictors of familial cancer: the corresponding OR(95%CI) and P-value were 0.974(0.963-0.985) and 0.000; 1.271(1.053-1.535) and 0.012; and 4.265(2.535-7.176) and 0.000, respectively.CONCLUSION: Patients with ESCC and a positive family history of the cancer had a significantly younger onset age and more multiple primary cancers than those without a positive family history. Sub-group analyses indicated that younger onset age may be due to the interaction of genetic predisposition and environmental hazards, and multiple primary cancers may only be due to genetic predisposition.
文摘AIM:To investigate the epidemiological characteristics of colorectal cancer(CRC)in patients under 50 years of age across two institutions.METHODS:Records of patients under age 50 years of age who had CRC surgery over a 16 year period were assessed at two institutions.The following documents where reviewed:admission notes,operative notes,and discharge summaries.The main study variables included:age,presenting symptoms,family history,tumor location,operation,stage/differentiation of disease,and post operative complications.Stage of disease was classified according to the American Joint Committee on Cancer TNM staging system:tumor depth;node status;and metastases.RESULTS:CRC was found in 180 patients under age50 years(87 females,93 males;mean age 41.4±6.2years).Young patients accounted for 11.2%of cases during a 6 year period for which the full data set wasavailable.Eight percent had a 1stdegree and 12%a 2nd degree family CRC history.Almost all patients(94%)were symptomatic at diagnosis;common symptoms included:bleeding(59%),obstruction(9%),and abdominal/rectal pain(35%).Evaluation was often delayed and bleeding frequently attributed to hemorrhoids.Advanced stage CRC(Stage 3 or 4)was noted in 53%of patients.Most tumors were distal to the splenic flexure(77%)and 39%involved the rectum.Most patients(95%)had segmental resections;6 patients had subtotal/total colectomy.Poorly differentiated tumors were noted in 12%and mucinous lesions in 19%of patients of which most had Stage 3 or 4 disease.Twenty-two patients(13%)developed recurrence and/or progression of disease to date.Three patients(ages 42,42and 49 years)went on to develop metachronous primary colon cancers within 3 to 4 years of their initial resection.CONCLUSION:CRC was common in young patients with no family history.Young patients with symptoms merit a timely evaluation to avoid presentation with late stage CRC.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30700813, No. 30470977, No, 30080016）, Fundamental Key Science Foundation of Science and Technology Commission of Shanghai Municipality （No. 05JC14029）, Public Scientific Sesearch Platform of Hospital of Grade A at the Tertiary Level of Shanghai （No. SHDC12007704） and Youth Science Foundation of Shanghai Health Bureau （No. 034Y03）.Acknowledgments： We thank CapitalBio Corporation for performing microarray scanning and Jacqueline Ramirez, Keith Mitchilson for editorial comments.
文摘Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes （TSGs）. However, the mechanism of colorectal cancer （CRC） is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis. Methods Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity （LOH） mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients＇ tumor and normal DNA were analyzed via polymerase chain reaction （PCR） for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases. Results The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% （18/49） at D1S2622, and the lowest of 16.42% （11/67） at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data （patient sex, age, tumor size, growth pattern, or Dukes stage）. On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 （1q31.3-32.1） region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4
文摘Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC.During the past two decades,sporadic CRCs were classified into three major groups according to frequently altered/mutated genes.These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data.In the first half of this review,we describe the genetic pathways of sporadic CRCs and their clinicopathologic features.Recently,large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes.These infrequently mutated genes are likely described in a limited number of pathways.Gene-oriented models of CRC progression are being replaced by pathway-oriented models.In the second half of this review,we summarize the present knowledge of this research field and discuss its prospects.
