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。     

遗传性非息肉病性结直肠癌的临床诊治

基于现代生物学和流行病学的研究，日渐明确大肠癌是由遗传、生活习惯、饮食和环境等多因素协同作用的结果，是由致癌物的作用结合细胞的遗传背景，诱发细胞遗传突变而逐步发展而成的［１］。一般根据发生人群的不同，可将大肠癌归纳为以下五大类：①散发性大肠癌（ｓｐｏ...     

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。     

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.     

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相关肿瘤累计危险度分析

目的 了解各遗传性非息肉病性结直肠癌（HNPCC）相关肿瘤在中国HNPCC家族中发病的危险度,探讨中国HNPCC患者的诊断和治疗策略.方法 收集符合Amsterdam标准的HNPCC家族41个,以寿命表法对213例发生各种肿瘤的HNPCC家族成员做相关肿瘤的累计危险度分析.结果 肠外肿瘤中胃癌发生率最高（25例）,其次为子宫内膜癌（11例）.各HNPCC常见肿瘤的累计危险度分别为大肠癌89.5%,胃癌24.5%,子宫内膜癌29.6%（女性）,肝癌8.2%.结论 肠外肿瘤中胃癌、子宫内膜癌及肝癌的累计危险度均较高,忽视胃癌在中国HNPCC诊断中的价值,可能会漏诊部分患者.     

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

遗传性非息肉病性结直肠癌(HNPCC)是一种由错配修复(MMR)基因突变造成的常染色体显性遗传病.作为大肠癌的一个重要临床亚型,HNPCC约占全部大肠癌的5%～15%.MMR基因的种系突变和微卫星不稳定(MSI)是其分子遗传学基础.由于HNPCC的遗传病因特殊、临床病理特点突出,是目前大肠癌和遗传性肿瘤的研究热点.     

遗传性非息肉病性结直肠癌

Hereditary non-polyposis colorectal cancer(HNPCC) is an autosomal-dominantly inherited disease which is associated with germline mutations in mismatch repair(MMR) genes and microsatellite instability (MSI). As an important clinical subtype of colorectal cancer, HNPCC is accounting for 5%～15% of colorectal cancer. It' s focus research of colon cancer and hereditary tumor currently because of the special genetic etiopathogenisis and the prominent clinical pathology characteristic.     

遗传性非息肉病性结直肠癌

Hereditary non-polyposis colorectal cancer(HNPCC) is an autosomal-dominantly inherited disease which is associated with germline mutations in mismatch repair(MMR) genes and microsatellite instability (MSI). As an important clinical subtype of colorectal cancer, HNPCC is accounting for 5%～15% of colorectal cancer. It' s focus research of colon cancer and hereditary tumor currently because of the special genetic etiopathogenisis and the prominent clinical pathology characteristic.     

遗传性非腺瘤病性结直肠癌的诊治进展

遗传性非腺瘤病性结直肠癌（HNPCC）是一种常染色体显性遗传的综合症,占总的结直肠癌的56%--10%。该病由错配修复基因缺陷造成,肿瘤表现出高度的微卫星不稳。临床上辨别HNPCC患者对诊断和治疗以及监测HNPCC家庭成员发病有指导意义。     

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。     

Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome

The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32-60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment.     

Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer

Endometrial carcinoma (EC) is the most common extracolonic tumor associated with hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC increases the risk of EC compared to the general population. Patients with HNPCC have a better prognosis than patients with common sporadic colorectal cancer. It is unknown, however, whether the survival rate of HNPCC-associated EC is higher than that of sporadic EC. The aim of our study was to compare the survival rates of HNPCC-associated EC with sporadic EC. From the registry of the Netherlands Foundation for Hereditary Tumors, 50 patients with HNPCC-associated EC from 46 families harboring a germline mutation or fulfilling the Amsterdam Criteria II were age- and stage-matched with 100 patients with sporadic EC registered in the Eindhoven Cancer Registry in the Netherlands. Survival rates were analyzed. The overall 5-year cumulative survival rates for patients with HNPCC-associated EC was 88% and 82% for patients with sporadic EC (p = 0.59). In Stages IA, IB and IC, the survival rates of patients with HNPCC-associated EC and sporadic EC were 92% and 91%, respectively (p = 0.90). In Stages IIIA and IIIC, the survival rates for HNPCC-associated EC and sporadic EC were 72% and 50%, respectively (p = 0.38). Furthermore, there was no significant difference in the distribution of tumor histologic subtypes in the study and control groups (p = 0.55). The outcomes in survival in EC in the general population and in women from families with HNPCC do not differ significantly. These results may have important implications in our understanding of EC and the role of early screening.     

Use of microsatellite analysis in young patients with colorectal cancer to identify those with hereditary nonpolyposis colorectal cancer

BACKGROUND AND OBJECTIVES: The frequency of microsatellite instability (MSI) in young patients with colorectal cancer was evaluated, including reexamination of the medical and family history of each patient, and interviews with the patients to determine any possible new occurrence of hereditary nonpolyposis colorectal cancer (HNPCC) in the patients themselves or their family members. METHODS: Fifty-three young patients (younger than 40 years of age) with colorectal cancer were selected and investigated. DNA was extracted from paraffin sections and microsatellite analysis was performed. RESULTS: The frequency of MSI among the young patients with colorectal cancer was 50.9%, which was significantly higher than the rate of 12-21% noted in older patients with colorectal cancer (P < 0.001). For the 24 young patients with colorectal cancer who did not have MSI, only one case of HNPCC kindred and two cases with a family history of cancer were identified. In contrast, among the 20 young patients with colorectal cancer who had MSI, five cases of HNPCC kindred, two cases with metachronous patients with colorectal cancer, and three cases with a family history of cancer were identified. CONCLUSION: Our results suggest that a defect in the DNA mismatch repair system may play some role in carcinogenesis in young patients with colorectal cancer. Microsatellite analysis and subsequent interviews regarding medical and family history are useful tools for efficiently identifying possible cases of HNPCC among young patients with colorectal cancer.     

检测微卫星不稳在中国遗传性非息肉病性结直肠癌患者诊断中的应用

背景与目的：遗传性非息肉病性结直肠癌（hereditary nonpolyposis colorectal cancer，HNPCC）是常染色体显性遗传综合征，国外报道90％的HNPCC肿瘤表现为微卫星不稳（microsatellite instability，MSI），可作为筛查HNPCC的金标准。本研究旨在了解中国HNPCC肿瘤MSI发生率以及可疑HNPCC患者大肠癌肿瘤中的MSI发生率，由此探讨大肠癌患者家族中的胃癌等HNPCC相关肿瘤对发现HNPCC患者的意义。方法：选择符合Amsterdam标准的HNPCC组大肠癌标本18例，和不符合Amsterdam标准、但高度怀疑为HNPCC的可疑HNPCC组大肠癌标本16例，检测BAT26、D2S123、BAX、IGFIIR、hMSH3和hMSH66个做卫星位点的微卫星不稳在两组中的发生率，比较两组微卫星不稳频率的差异。结果：上述各傲卫星位点在HNPCC组和可疑HNPCC组标本中均显示较高的突变率。高度微p星不稳肿瘤在两组标本中的检出率分别为94．4％和93．7％．差异无显著性。BAT26对高度微卫星不稳肿瘤敏感度高。结论：MSI在中国HNPCC患者中的发生频率与国外类同。仅用BAT26可发现大部分高度微卫星不稳肿瘤。将胃癌等HNPCC相关肿瘤纳入临床诊断标准，可能有助于避免在中国大肠癌人群中漏诊HNPCC患者。     

Colon cancer screening practices and disclosure after receipt of positive or inconclusive genetic test results for hereditary nonpolyposis colorectal cancer

BACKGROUND:

Patients who receive conclusive genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) tend to adopt appropriate colorectal cancer screening behaviors and disclose their test results. However, little is known about the disclosure processes or screening behaviors of individuals who receive inconclusive genetic test results. This study compared endoscopy use and disclosure between individuals with positive and inconclusive genetic test results, within a year after results were received.

METHODS:

Individuals with a personal history of cancer and suspected of having HNPCC participated in genetics education and counseling, underwent HNPCC testing, and received genetic test results (GCT) within a prospective cohort study. Demographic, psychosocial, and behavioral data were obtained from questionnaires and interviews completed before and after GCT.

RESULTS:

Index cases with inconclusive genetic test results were less likely to screen within 12 months. Index cases who disclosed test results to children within 6 months were more likely to screen within 12 months, controlling for mutation status. Index cases with inconclusive genetic test results were less likely to share results with a healthcare provider within 6 months. Index cases who disclosed genetic test results to healthcare providers within 6 months were more likely to have endoscopy within 12 months.

CONCLUSIONS:

Genetic test results and disclosure significantly affected colon cancer screening at 12‐month follow‐up. Interventions to improve adherence to colorectal cancer screening should consider increased education of those receiving inconclusive results and encourage disclosure to healthcare providers and family members. Cancer 2009. Published 2009 by the American Cancer Society.     

Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation‐negative familial ovarian cancers

BACKGROUND:

Inherited mutations account for approximately 10% of all epithelial ovarian cancers. Breast cancer (BRCA1 and BRACA2) gene mutations are responsible for up to 85% of inherited breast and/or ovarian cancer. Another condition that has been associated with ovarian cancer is hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which carries a lifetime risk of up to 13% for ovarian cancer. The objective of this study was to determine the incidence of HNPCC‐related gene mutations in patients with familial ovarian cancer who previously tested negative for BRCA1 and BRCA2 gene mutations.

METHODS:

Seventy‐seven probands were identified who had familial ovarian cancer and negative BRCA gene mutation testing. Their pedigrees were analyzed for HNPCC syndrome. DNA samples underwent gene sequencing and Southern blot analysis for mutations in the 3 most common HNPCC‐associated genes: mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) with reflex testing for MSH6 if tests for the first 2 genes were negative.

RESULTS:

None of the probands met Amsterdam criteria for the clinical diagnosis of HNPCC. DNA testing revealed 2 patients (2.6%) with deleterious mutations in the MSH2 gene. An additional 8 patients (10.4%) had substitutions in either the MLH1 gene or the MSH2 gene that were classified as variants of uncertain significance. If Amsterdam criteria were expanded to include ovarian cancer, then 15 of 77 patients (19.5%) would have met these expanded criteria. One deleterious mutation was noted in this group, yielding a mutation incidence of 6.7%. This percentage may be even higher if any of the identified variants of uncertain significance are confirmed to be deleterious.

CONCLUSIONS:

HNPCC should be considered when evaluating patients with suspected hereditary ovarian cancer who have had negative BRCA mutation testing. Cancer 2009. © 2009 American Cancer Society.     

Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred

Endoglin (CD105) is a proliferation-associated protein that is strongly expressed in endothelial tissue and has a role in tumor angiogenesis. Mutations in endoglin are also linked to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disease associated with aberrant angiogenesis. We report an unusual association of HHT1 and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in the same kindred. Genetic analysis indicates that these 2 syndromes are genetically unrelated and separately segregated within the family. The mutation in the endoglin gene leads to a truncated protein. The mutation in the mismatch repair gene MLH1 causes a splicing defect, giving synthesis to an unstable mRNA from this mutated allele. The potential protective role of an endoglin mutation in patients with HNPCC is discussed.