遗传性非息肉病性大肠癌

目的：探讨总结遗传性卢肉病性大肠癌（ＨＮＰＣＣ）的特征,提高早期诊断和治疗水平。方法：复习文献并本结合本组四个家族的临床资料进行总结分析。结果：ＨＮＰＣＣ发病年龄轻,平均发病年龄４４岁,约６５％的患者病变发生在曲近侧结肠;约２５％的患者有多原发大肠癌;２０～７０％的患者可检测到错配修复基因（ＭＭＲ）的突变;病理分化差但有较好的预后。结论：ＨＮＰＣＣ有明显的特征,利用这些特征有助于早期诊断和制定合理     

遗传性非息肉病性大肠癌11个家系32例的临床特点与诊治

目的：分析遗传性非息肉病性大肠癌的临床特点及诊治经验。方法：分析11个家系32例遗传性非息肉病性大肠癌的诊断、治疗、随访结果，分别记录肿瘤发病部位、病理结果等一般情况。结果：11个家系中共有恶性肿瘤43例61个肿瘤，其中大肠癌32例39个肿瘤。32例中至今共发生异时多原发恶性肿瘤12例，占37．5％，其中异时多原发大肠癌5例，占15．6％。通过先证者对其本人及一级亲属进行随诊检查共发现各类恶性肿瘤28个，其中20个(67．7％)为无明显临床症状者。结论：本病是一种常染色体显性遗传病，本病具有发病年龄早，好发于近侧结肠，易患异时或同时多原发癌及大肠外恶性肿瘤。在诊治中要作详细病史调查，除对先证者进行治疗和随访外．对其亲属的宣教和随访等工作亦十分重要。     

遗传性非息肉病性大肠癌和普通遗传性大肠癌临床表型分析

目的:探讨遗传性非息肉病性大肠癌(HNPCC)与普通遗传性大肠癌临床表型的异同,为临床辨认HNPCC家系提供依据。方法:选择符合阿姆斯特丹标准Ⅱ或日本标准的22个HNPCC家系(A组)和普通遗传性大肠癌20个家系(B组)为研究对象进行随访分析。结果:1)A、B两组男女发病的比例分别为1.4:1(41/30)和1.5:1(38/26),无显著性差异(P>0.05)。2)A、B两组确诊的中位年龄分别为48岁(32～70岁)和61岁(30～83岁),50岁以前发病比例分别为59.2%和26.6%,A组较B组发病年龄明显提前,差异显著(P<0.01)。3)A、B两组右半结肠癌发病比例分别为56.9%(29/51)和29.2%(7/24),差异显著(P<0.05)。4)A组多发癌7例,B组未见多发癌。5)A组第一、二、三代的平均发病年龄分别为64岁、56岁、48岁,逐渐年轻化,B组无此现象。结论:HNPCC与普通遗传性大肠癌临床表型不尽相同,提示两者各自有其独特的遗传学特征。     

遗传性非息肉病性大肠癌的诊治进展

遗传性非息肉病性结直肠癌（HNPCC）是一种常染色体显性遗传病，错配修复基因的种系突变是发病基础，在散发性大肠癌中遴选HNPCC家族，并对HNPCC患者对其家属进行基因检测可以发现HNPCC相关肿瘤的高危人群，使家族中发病率低的成员免受长期医疗随访之苦，而且对HNPCC相关肿瘤患者进行预防性手术有较大的临床意义。     

2例遗传性非息肉病性大肠癌家系分析

目的分析2例遗传性非息肉病性大肠癌（HNPCC）家系的临床病理特征。方法对2个HNPCC家系进行病例回顾及家系调查。结果HNPCC的主要特点是病灶好发于右半结肠，发病年龄较轻，预后好于散发性大肠癌。结论应对HNPCC患者及其家族严密监测、随访，以便早期诊断、及时治疗、改善预后。     

遗传性非息肉病性结直肠癌家系分析

目的　探讨遗传性非息肉病性结直肠癌在我国的发病遗传规律以及流行病学特点。方法　自 1999年 1月至 2 0 0 2年 12月 ,对天津市人民医院 (原名天津市滨江医院 )收治的 2 92例结直肠癌患者进行家系调查 ,从中筛选出符合以下标准的遗传性非息肉病性结直肠癌家系 3 8个 ,对家系的肿瘤发生率、肿瘤谱和临床特点等进行了分析和总结。诊断标准使用Amsterdam标准Ⅰ、Amsterdam标准Ⅱ (ICG HNPCC)和日本HNPCC诊断标准。结果　 3 8个遗传性非息肉病性结直肠癌家系中共有 14 5例癌症患者 ,其中男性 76例 ,女性 69例 ,男女比例为 1.1∶1。原发性结直肠癌平均诊断年龄为 ( 5 5 .73± 15 .88)岁 ,在所有 99例结直肠癌中 ,左半结肠癌及直肠癌 2 9例 ,占 2 9.3 % ;右半结肠癌 70例 ,占 70 .7% ,右半结肠癌占有绝对的优势 ;异时性多发性原发结直肠癌患者占大肠癌患者的 13 .1% ( 13 /99) ;HNPCC相关肿瘤共 46例其发生率由高到低前三位是 :子宫内膜癌 9例 ( 19.6% )、乳腺癌 7例 ( 15 .2 % )、肺癌、胃癌各 6例 ( 13 .0 % ) ;在男女性共患癌中 ,除胰腺癌、纵隔癌外 ,男性发生率均高于女性 ;第一代、第二代以及第三代患者的平均诊断年龄有逐渐年轻化的趋势 ,并具有统计学意义。结论　我国遗传性非息肉病性结直肠癌很可能     

遗传性非息肉病性结直肠癌的研究进展

遗传性非息肉病性结直肠癌（ｈｅｒｅｄｉｔａｒｙｎｏｎ－ｐｏｌｙｐｏｓｉｓｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ，ＨＮＰＣＣ）是一种常染色体显性遗传性肿瘤，外显率高达８０％～８５％，约占所有大肠癌的５％～１５％。与一般散发性大肠癌相比，它在临床表现、病理学检查和遗传背景上都有着独特的特征，其诊断主要根据临床与家系表征而定。近年来关于ＨＮＰＣＣ的国内外研究范围有新的积累，获得了一些新的认识和看法。１国际诊断标准的确立与修改为了规范和统一ＨＮＰＣＣ的诊断，便于世界范围内的协作研究，１９９０年国际ＩＣＧ－ＨＮ…     

遗传性非息肉病性结直肠癌7个家系的临床分析

目的：总结遗传性非息肉病性结直肠癌（HNPCC）家系的临床特点,提高临床诊断和治疗水平。方法：收集7个HNPCC家系的病例资料,分析其发病特点并记录随访结果。结果：7个HNPCC家系共有癌症患者23例,肿瘤灶27处：大肠外瘤灶3处;大肠瘤灶24处,其中有13处位于脾曲近侧结肠,占54.1%。平均发病年龄为41.2岁,17例（73.5%）发病在50岁以前。1家系累及连续三代人、4家系累及连续两代人。多原发癌患者4例,其中3例为肠外癌。结论：HNPCC具有发病年龄轻、垂直传递、肠外癌发病率高、常见多原发癌、好发于右半结肠、病理分化较差的特点,但预后相对较好。     

遗传性非息肉病性大肠癌分子机理研究进展

大肠癌是我国常见的恶性肿瘤,以往研究表明其发生常涉及等位基因的杂合性缺失(loseofhetero-zygosity,LOH)这一途径,并与多个癌基因和抑癌基因的突变有关。近年来对遗传性非息肉病性结直肠癌(hereditarynon-polyposiscolorectalcancer,HNPCC)的发现和研究,使人们对大肠癌的发生机制有了新的认识。1913年Warthin首次描述了HNPCC的临床病理特征,并报道了一些胃癌、大肠癌聚集的家系。但直到半世纪后,Lynch等才更详细地描述了这些家系的遗传和临床病理学特征,并根据是否发生肠外肿瘤将其分为LynchI和Lynch型。因此,HNPCC又被称为Lync…     

遗传性非息肉病性大肠癌两种手术方式疗效分析

目的:探讨遗传性非息肉病性大肠癌理想的手术方式.方法:回顾性分析1990年8月～2002年8月我院普外科收治的31例遗传性非息肉病性大肠癌的临床资料,17例接受大肠癌次全切术,14例接受大肠癌常规手术.比较手术前、后患者体重、血浆营养参数(血红蛋白、血清白蛋白)以及术后排便次数、术后复发率在两种手术方式组间的差异.结果:患者的体重变化、血红蛋白、血浆蛋白的变化及术后每天排便次数在两种术式组中无明显差异(P＞0.05);次全大肠切除术组复发率比常规手术方式组低,二者相比具有统计学差异(P＜0.05).结论:次全结肠切除术较大肠癌常规手术更适合于遗传性非息肉病性大肠癌的治疗.     

遗传性非息肉病结直肠癌的诊治

目的：探讨遗传性非息肉病结直肠癌（HNPCC）患者家族成员的患病特点。方法：对11个HNPCC家族进行调查分析。结果：11个HNPCC家族中有41例大肠癌患者，1例合并子宫内膜癌，共有大肠癌灶49处，其中多原发癌6例，平均发病年龄41．5岁，结论：HNPCC具有发病年龄轻，好发于近侧结肠，同时或异时大肠癌比较高及易发生其他器官癌的特点，对HNPCC患者及其亲属进行密切随访和定期检测，对其早期诊断和治疗有重要意义。     

Hereditary Colorectal Cancer in China

The purpose of this article is to review basic research as well as clinical studies on Chinese hereditary colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) accounts for 2.2% of all colorectal cancer, and Chinese criteria for suspected HNPCC have been developed. Germline mutations as well as large genomic rearrangements of mismatch repair (MMR) genes are responsible for this syndrome. Gastric cancer is the second most common cancer in Chinese HNPCC patients. Contrary to sporadic colorectal cancer in the Chinese population, HNPCC does not typically present with rectal cancer. Incidence of familial adenomatous polyposis (FAP) in China is approximately 1.5/100,000. Polyps in Chinese FAP patients can emerge as early as 16 months old, but malignant transformation usually occurs in the third and fourth decade. Total resection of the colon and rectum is necessary in FAP patients. For unresectable duodenal polyps, chemopreventive agents may be used.     

遗传性非息肉病性结直肠癌家系肿瘤谱特点分析

目的: 探讨中国人遗传性非息肉病性结直肠癌肿瘤谱特点,为诊断提供依据. 方法: 对收集的69个HNPCC家系(符合Amsterdam标准Ⅱ33个、Japan标准24个、Bethesda指导原则1～3项12个)肿瘤谱特点进行分析. 结果: 69个家系共有癌症患者277人,其中肠癌患者213人,占76.9%.肠外癌患者64人,占癌患者的23.1%,其中胃癌、子宫内膜癌分别占癌患者的6.5%和4%,列前两位. 结论: 肠癌在中国人HNPCC肿瘤谱中所占比例最高,其次为胃癌和子宫内膜癌.肠外癌谱是HNPCC家系的重要特点,对诊断有较大帮助.     

Frequency of Familial Colon Cancer and Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in a Large Population Database

Background and aims: Estimates have been made concerning the fraction of colorectal cancer (CRC) cases that meet Amsterdam I criteria but not Amsterdam II criteria. The aim of this study was to determine in a population setting what fraction of CRC cases can be considered familial high-risk, what fraction of these meet Amsterdam I or II criteria, and what fraction of CRC cases overall meet Amsterdam I and II criteria. Methods: The Utah Population Data Base (UPDB), which links Utah genealogies to the Utah Cancer Registry, was used to examine the aims of the study. Familial high-risk was operationally defined as CRC occurring at an age <50 years or as a part of a first-degree relative pair. A subset of Amsterdam positive cancers was tested for microsatellite instability (MSI) to determine what fraction of Amsterdam families was likely to have hereditary nonpolyposis colorectal cancer (HNPCC). Results: Of the 6,628 CRC cases in the UPDB, 24.5% met the criteria for familial high-risk. Of these, 2.6% met Amsterdam I criteria and 5.5% Amsterdam II. Of total data base CRC cases, 0.8% met Amsterdam I criteria and 2.3% Amsterdam II. In a subset of colon tumors from Amsterdam families, 70% were MSI stable. Conclusions: Although nearly 25% of CRC cases in our population data base met a simple definition of familial high-risk, only a small fraction of these and a smaller fraction of total CRC cases met Amsterdam I or II criteria. Less than half of a limited set of tumors from Amsterdam families were MSI positive.     

MMR蛋白在云南地区遗传性非息肉病性 大肠癌中的表达及意义

 目的探讨MLH1、MSH2、PMS2和MSH6蛋白在云南地区遗传性非息肉病性大肠癌（hereditary nonpolyposis colorectal cancer,HNPCC）中的表达及意义。方法根据目前国内外通常采用的三个标准在 云南地区选择遗传性非息肉病性大肠癌病例13个家系中19例肿瘤组织,应用免疫组织化学方法（IHC）检 测MLH1、MSH2、PMS2和MSH6蛋白。结果在这13个家系中,MLH1、MSH2、PMS2和MSH6四种蛋白表达缺失率分 别为30.77%、38.46%、23.08%、15.38%,其中2例家系先证者同时存在MLH1和PMS2蛋白表达缺失,2例家系 先证者同时存在MSH2和MSH6蛋白表达缺失,四种MMR蛋白总的表达缺失率为84.62%。结论云南地区HNPCC病 例存在MLH1、MSH2、PMS2和MSH6 四种MMR蛋白不同程度的缺失表达,应用IHC检测MMR蛋白可以作为筛选 HNPCC家系的一有效手段。     

遗传性非息肉病性大肠癌(10个家族27例报告)

分析遗传性非息肉病性大肠癌(HNPCC)的临床特点。方法:对10个家族27例HNPCC患者(A组)进行回顾性分析,并设30例一般大肠癌为对照组(B组)进行比较。结果:<50岁患者A组占59.3%(16/27),B组占23.3%(7/30),P<0.05。脾曲以上癌灶A组为40.0%(12/30),B组为16.1%(5/31),P<0.05。大肠多原发癌A组占10.0%(3/30),B组占3.2%(1/31)。大肠外肿瘤A组6例,B组2例。结论:HNPCC具有典型的临床特征,这些特征可以对HNPCC患者进行早期诊断及治疗,以得到较好的预后。     

Hereditary Colorectal Cancer (CRC) Program in Latvia

Introduction

The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes.

Materials and methods

From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis.

Results

From the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations.For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form.

Conclusions

Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

     

Microsatellite Instability and Frameshift Mutations in the Bax Gene in Hereditary Nonpolyposis Colorectal Carcinoma

We studied microsatellite instability (MI) and bax gene abnormalities in colorectal carcinomas from 36 patients diagnosed as having hereditary nonpolyposis colorectal cancers (HNPCC) according to the clinical criteria (12 with confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and from 20 randomly selected patients with other colorectal cancers. MI was examined at 4 dinucleotide microsatellite loci and one mononucleotide locus. Frameshift mutations in the bax gene were detected by polymerase chain reaction-single strand conformation polymorphism analysis. MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B. Three MI patterns were identified: type 1, MI in both mono- and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide repeats. Most MI-positive patients in group A showed type 1 MI, whereas in group B, 5 showed type 1, 3 showed type 2 and 4 showed type 3. Frameshift mutations in the bax gene correlated strongly with type 1 and type 2 MI. These results indicate that mutations of different DNA mismatch repair genes may cause several types of MI and result in several different clinical phenotypes of HNPCC. The bax gene may be one of the target genes which play a role in the tumorigenesis of HNPCC.     

Loss or Somatic Mutations of hMSH2 Occur in Hereditary Nonpolyposis Colorectal Cancers with hMSH2 Germline Mutations

Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2 . To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2 -related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.