Colorectal cancer(CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of...Colorectal cancer(CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression.展开更多
Despite the general decrease in overall incidence of colorectal cancer since the early 1990s,the incidence of colorectal cancer in patients less than 50 years old has nearly doubled.A systematic review was performed u...Despite the general decrease in overall incidence of colorectal cancer since the early 1990s,the incidence of colorectal cancer in patients less than 50 years old has nearly doubled.A systematic review was performed using the PubMed database(2011-2020)and Cochrane Database of Systematic Reviews(2011-2021)to identify studies(published in English)evaluating epidemiologic,clinical,hereditary,and molecular features;as well as evaluation,management,and prognosis of youngonset colorectal cancer patients.Our search yielded a total of 3401 articles,after applying our inclusion criteria.We fully reviewed 94 full-length studies.This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.展开更多
目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF...目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。展开更多
BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a ri...BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies.AIM To study tumor biology in CRC patients below 50 years of age.METHODS All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age(≥50 and<50 years).Clinical as well as histopathological features were analyzed and compared.The study was approved by the local Ethics Committee.Fisher’s exact test or t-test was used to test for differences between the groups,as appropriate.All statistical analysis was performed with IBM SPSS software Version 25(SPSS Inc,Armonk,NY,United States)and with RStudio using R Version 3.4.1(RStudio,Boston,MA,United States).RESULTS Seventeen percent of the 411 patients were younger than 50 years.Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases(36.6%and 62%vs 17.7%and 42%;P<0.01).In addition,a higher frequency of poorly differentiated(G3)tumors(40%vs 22.4%P<0.05)was observed.More than every second patient below 40 years of age(51.8%)had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients≥50 years(14.8%,P<0.05).Mutational status(KRAS,NRAS,BRAF,MSI)as well as selected behavioral risk factors showed no significant differences.CONCLUSION Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset.Those patients present more frequently with more advanced tumor stages compared to older patients.Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.展开更多
目的探讨非典型糖尿病（ADM）青年患者的临床特征。方法回顾性分析340例发病年龄≤40岁的糖尿病患者的病例资料。通过详细病史收集、体格检查及实验室检测,排除典型的1型糖尿病、2型糖尿病及其他类型糖尿病,共有20例患者符合ADM诊断标...目的探讨非典型糖尿病（ADM）青年患者的临床特征。方法回顾性分析340例发病年龄≤40岁的糖尿病患者的病例资料。通过详细病史收集、体格检查及实验室检测,排除典型的1型糖尿病、2型糖尿病及其他类型糖尿病,共有20例患者符合ADM诊断标准。对该组患者的发病特点、胰岛β细胞功能变化及糖脂代谢指标进行分析。结果在青年起病的ADM患者中,男性多发（男∶女=18∶2）;且新诊断的糖尿病及家族史比例偏高,分别占80.0%和70.0%。ADM患者空腹及餐后2 h C肽均介于1型及2型糖尿病患者之间。此外,ADM患者的Hb A1c及尿酸高于2型糖尿病患者（P=0.000,P=0.001）,而三酰甘油高于1型糖尿病患者（P=0.002）。在6～12个月的随访过程中,19例患者（占95.0%）终止胰岛素治疗;其中12例患者（占60.0%）仅靠控制饮食及运动即可维持血糖水平正常。结论青年ADM患者以男性多见,多为新诊断糖尿病患者且多有糖尿病家族史,常伴有脂代谢异常,胰岛β细胞功能修复能力较好。展开更多
文摘Colorectal cancer(CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression.
文摘Despite the general decrease in overall incidence of colorectal cancer since the early 1990s,the incidence of colorectal cancer in patients less than 50 years old has nearly doubled.A systematic review was performed using the PubMed database(2011-2020)and Cochrane Database of Systematic Reviews(2011-2021)to identify studies(published in English)evaluating epidemiologic,clinical,hereditary,and molecular features;as well as evaluation,management,and prognosis of youngonset colorectal cancer patients.Our search yielded a total of 3401 articles,after applying our inclusion criteria.We fully reviewed 94 full-length studies.This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.
文摘目的·筛查青少年的成人起病型糖尿病(maturity-onset diabetes of the young,MODY)家系中NEUROD1基因突变,分析突变与中国人MODY6发病的相关性及其潜在的致病机制。方法·采用PCR-直接测序法对96例GCK/MODY2、HNF1A/MODY3、HNF1B/MODY5突变阴性的中国MODY先证者进行NEUROD1突变筛查,同时比较96例MODY先证者与100例非糖尿病对照者NEUROD1基因变异的基因型频率。采用从头建模法构建NEUROD1蛋白野生型和突变体的3D结构,采用双荧光素酶报告基因系统检测野生型和突变体蛋白对胰岛素基因转录活性的影响。结果·在一个MODY家系中发现NEUROD1基因杂合错义突变Glu59Gln (NM_002500.5,c.175G>C)。3D结构分析发现,该突变将野生型中带负电荷的Glu59转化为突变中不带电荷的Gln59,导致两个盐桥键Glu59-Arg54和Glu59-Lys88缺失,并形成一个新的氢键Gln59-Arg54。与野生型相比,Glu59Gln突变体的胰岛素基因转录活性下降36.3%(P<0.05)。与非糖尿病对照相比,96例MODY先证者中Ala45Thr (G-A)变异的AA+GA基因型频率显著升高(P=0.002)。结论·Glu59Gln突变改变了NEUROD1蛋白N端的分子构象,导致其胰岛素基因转录活性显著下降,是该家系突变携带者胰岛素分泌缺陷的原因。Ala45Thr变异与MODY6先证者糖尿病发病年龄的提前有关。
文摘BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies.AIM To study tumor biology in CRC patients below 50 years of age.METHODS All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age(≥50 and<50 years).Clinical as well as histopathological features were analyzed and compared.The study was approved by the local Ethics Committee.Fisher’s exact test or t-test was used to test for differences between the groups,as appropriate.All statistical analysis was performed with IBM SPSS software Version 25(SPSS Inc,Armonk,NY,United States)and with RStudio using R Version 3.4.1(RStudio,Boston,MA,United States).RESULTS Seventeen percent of the 411 patients were younger than 50 years.Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases(36.6%and 62%vs 17.7%and 42%;P<0.01).In addition,a higher frequency of poorly differentiated(G3)tumors(40%vs 22.4%P<0.05)was observed.More than every second patient below 40 years of age(51.8%)had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients≥50 years(14.8%,P<0.05).Mutational status(KRAS,NRAS,BRAF,MSI)as well as selected behavioral risk factors showed no significant differences.CONCLUSION Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset.Those patients present more frequently with more advanced tumor stages compared to older patients.Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.
文摘目的探讨非典型糖尿病（ADM）青年患者的临床特征。方法回顾性分析340例发病年龄≤40岁的糖尿病患者的病例资料。通过详细病史收集、体格检查及实验室检测,排除典型的1型糖尿病、2型糖尿病及其他类型糖尿病,共有20例患者符合ADM诊断标准。对该组患者的发病特点、胰岛β细胞功能变化及糖脂代谢指标进行分析。结果在青年起病的ADM患者中,男性多发（男∶女=18∶2）;且新诊断的糖尿病及家族史比例偏高,分别占80.0%和70.0%。ADM患者空腹及餐后2 h C肽均介于1型及2型糖尿病患者之间。此外,ADM患者的Hb A1c及尿酸高于2型糖尿病患者（P=0.000,P=0.001）,而三酰甘油高于1型糖尿病患者（P=0.002）。在6～12个月的随访过程中,19例患者（占95.0%）终止胰岛素治疗;其中12例患者（占60.0%）仅靠控制饮食及运动即可维持血糖水平正常。结论青年ADM患者以男性多见,多为新诊断糖尿病患者且多有糖尿病家族史,常伴有脂代谢异常,胰岛β细胞功能修复能力较好。
