유전성 대장암

김덕우(Duck-Woo Kim) 대한의학유전학회 2010 대한의학유전학회지 Vol.7 No.1

대장암은 우리나라에서 가장 급격하게 발생이 증가하는 암종의 하나로 유전성 대장암은 전체 대장암의 5-15%를 차지한다. 유전성 대장암은 크게 유전성 비용종증 대장암과 유전성 용종 증후군에서 발생하는 대장암으로 나눌 수 있고, 유전성 용종 증후군에는 가족성 용종증, 포이츠-예거 증후군, 유년기 용종증, MYH 연관 용종증 등이 이에 해당한다. 유전성 대장암은 원인 유전자의 배선돌연변이에 기인하므로 산발성 대장암에 비하여 암이 조기 발생하고, 동시성 및 이시성 암이 흔하며, 대장 이외의 장기에도 종양을 비롯한 질병을 일으키는 특징이 있다. 유전성 대장암은 환자뿐 아니라 가족구성원에 대한 유전자 검사, 유전 상담, 조기 진단을 위한 정기 검진이 매우 중요하며, 이러한 환자 및 가족구성원의 효율적 관리를 위한 유전성종양 등록소의 역할이 중요하다. 본 논문에서는 유전성 대장암에 해당하는 질환들의 임상적/유전적 특성, 치료, 유전자 검사 및 정기검진 프로그램에 대하여 고찰하고자 한다. Colorectal cancer is one of the most steeply increasing malignancies in Korea. Among 398,824 new patients recorded by the Korea Central Cancer Registry between 2003 and 2005, 47,915 cases involved colorectal cancers, accounting for 12.0 % of all malignancies. In 2002, total number of colorectal cancer cases had accounted for 11.2 % of all malignancies. Hereditary syndromes are the source of approximately 5% to 15% of overall colorectal cancer cases. Hereditary colorectal cancers are divided into two types: hereditary nonpolyposis colorectal cancer (HNPCC), and cancers associated with hereditary colorectal polyposis, including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis, and the recently reported hMutYH (MYH)-associated polyposis (MAP). Hereditary colorectal cancers have unique clinical features distinct from sporadic cancer because these are due to germline mutations of the causative genes; (ⅰ) early age-of-onset of cancer, (ⅱ) frequent association with synchronous or metachronous tumors, (ⅲ) frequent association with extracolonic manifestations. The management strategy for patients with hereditary colorectal cancer is quite different from that for sporadic cancer. Furthermore, screening, genetic counseling, and surveillance for at-risk familial member are also important. A well-organized registry can plays a central role in the surveillance and management of families affected by hereditary colorectal cancers. Here, we discuss each type of hereditary colorectal cancer, focusing on the clinical and genetic characteristics, management, genetic screening, and surveillance.

Genes and SNPs Associated with Non-hereditary and Hereditary Colorectal Cancer

Nassiri, Mohammadreza,Kooshyar, Mohammad Mahdi,Roudbar, Zahra,Mahdavi, Morteza,Doosti, Mohammad Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, $XRCC_3$, $DNMT_1$, MTHFR, Exo1, $XRCC_1$ and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer. Materials and Methods: In this article we reviewed the Genes and SNPs associated with non-hereditary and hereditary of colorectal cancer that recently were reported from candidate gene y, meta-analysis and GWAS studies. Results: As with other cancers, colorectal cancer is associated with SNPs in gene loci. Generally, by exploring SNPs, it is feasible to predict the risk of developing colorectal cancer and thus establishing proper preventive measures. Conclusions: SNPs of genes associated with colorectal cancer can be used as a marker SNP panel as a potential tool for improving cancer diagnosis and treatment planning.

Screening and surveillance for hereditary colorectal cancer

( Hee Man Kim ),( Tae Il Kim ) 대한장연구학회 2024 Intestinal Research Vol.22 No.2

Hereditary colorectal cancer is a type of cancer that is caused by a genetic mutation. Individuals with a family history of colorectal cancer, or who have a known hereditary syndrome, are at an increased risk of developing the disease. Screening and surveillance are important tools for managing the risk of hereditary colorectal cancer. Screening involves a combination of tests that can detect precancerous or cancerous changes in the colon and rectum. Surveillance involves regular follow-up examinations to monitor disease progression and to identify new developments. The frequency and type of screening and surveillance tests may vary depending on an individual’s risk factors, genetic profile, and medical history. However, early detection and treatment of hereditary colorectal cancer can significantly improve patient outcomes and reduce mortality rates. By implementing comprehensive screening and surveillance strategies, healthcare providers can help individuals at risk of hereditary colorectal cancer to receive timely interventions and make informed decisions about their health. Specific examples of screening and surveillance tests for hereditary colorectal cancer include colonoscopy, genetic testing, and imaging tests. In this review article, we will discuss detailed screening and surveillance of hereditary colorectal cancer. (Intest Res 2024;22:119-130)

최신임상강좌 : 부인과 영역에서 유전성 종양의 임상적 접근

이채형 ( Chae Hyeong Lee ),노주원 ( Ju Won Roh ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.1

Hereditary cancer syndrome is a genetic condition that causes and increases the risk for specific type of cancers. Recent advances in genetics have identified a number of genes associated with inherited susceptibility to cancer, and this rapid development of knowledge about cancer genetics have implications for all aspects of cancer management, including prevention, screening, and treatment. Hereditary patterns of cancer are often characterized by early age at onset, high penetrance, bilaterality in paired organs, vertical transmission through either parent, and an association with other types of tumors. Most representative hereditary cancer syndromes in gynecologic field are hereditary breast/ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, and Cowden syndrome. Several familial mutations of specific genes, such as BRCA1, 2, TP53, PTEN, MMR, CHEK2, are linked to hereditary cancer syndrome, which are responsible for hereditary gynecologic cancers. It would be very important for gynecologic doctors to know the inclusion criteria for the genetic assessment, taking family history, clinical evaluation, genetic testing, screening guideline and risk reduction strategies for women with hereditary high risk factor. The morbidity and mortality of gynecologic malignancies related to these syndromes could be reduced by the adequate clinical approach, although recent guidelines were developed with an acute awareness of the preliminary nature of much of our knowledge regarding the clinical application of the rapidly emerging field of molecular genetics, and with an appreciation for the need for flexibility when applying these guidelines to individual families.

Hereditary nonpolyposis colorectal cancer in endometrial cancer patients

Yoon, Sang Nam,Ku, Ja-Lok,Shin, Young-Kyoung,Kim, Kyung-Hee,Choi, Jin-Sung,Jang, Eun-Ja,Park, Hyoung-Chul,Kim, Duck-Woo,Kim, Min A.,Kim, Woo Ho,Lee, Taek Sang,Kim, Jae Weon,Park, Noh-Hyun,Song, Yong-S Wiley Subscription Services, Inc., A Wiley Company 2008 International journal of cancer: Journal internati Vol.122 No.5

<P>Endometrial cancer is the second most common cancer in hereditary nonpolyposis colorectal cancer (HNPCC). It has often been overlooked to explore the possibility of HNPCC in endometrial cancer patients. Our study was to investigate how many HNPCC patients existed among endometrial cancer patients. Among patients who underwent hysterectomy for endometrial cancer at Seoul National University Hospital from 1996 to 2004, 113 patients were included, whose family history and clinical data could be obtained and tumor specimens were available for microsatellite instability (MSI) testing and immunohistochemical (IHC) staining of MLH1, MSH2 and MSH6 proteins. There were 4 (3.5%) clinical HNPCC patients fulfilling the Amsterdam criteria II, and 2 (2/4, 50%) of them carried MSH2 germline mutations. There were also 8 (7.1%) suspected HNPCC (s-HNPCC) patients fulfilling the revised criteria for s-HNPCC, and one (1/8, 12.5%) of them revealed MLH1 germline mutation. In 101 patients, who were not clinical HNPCC or s-HNPCC, 11 patients showed both MSI-high and loss of expression of MLH1, MSH2 or MSH6 proteins, and 2 (2/11, 18.2%) of them showed MSH6 germline mutations. In 113 patients with endometrial cancer, we could find 5 (4.4%) HNPCC patients with MMR germline mutation and 2 (1.8%) clinical HNPCC patients without identified MMR gene mutation. Family history was critical in detecting 3 HNPCC patients with MMR germline mutation, and MSI testing with IHC staining for MLH1, MSH2 and MSH6 proteins was needed in the diagnosis of 2 HNPCC patients who were not clinical HNPCC or s-HNPCC, especially for MSH6 germline mutation. © 2007 Wiley-Liss, Inc.</P>

한국인 유전성 비용종증 대장암의 임상적 특성

박영진,박규주,강구정,김광연,김성,김영진,김정용 대한대장항문학회 1998 Annals of Coloproctolgy Vol.14 No.1

hMLH1 promoter methylation and BRAF mutations in high-frequency microsatellite instability colorectal cancers not fulfilling the revised Bethesda guidelines

Sang Jin Kim,Hyoung Ran Kim,Seok Hyung Kim,Ji Hye Han,Yong Beom Cho,Seong Hyeon Yun,Woo Yong Lee,Hee Cheol Kim 대한외과학회 2014 Annals of Surgical Treatment and Research(ASRT) Vol.87 No.3

Purpose: Sporadic colorectal cancers with high-frequency microsatellite instability (MSI-H) are related to hypermethylation of mismatch repair (MMR) genes and a higher frequency of BRAF mutations than Lynch syndrome. We estimated the feasibility of hereditary colorectal cancer based on hMLH1 methylation and BRAF mutations. Methods: Between May 2005 and June 2011, we enrolled all 33 analyzed patients with MSI-H cancer (male:female, 23:10; mean age, 65.5 ± 9.4 years) from a prospectively maintained database that didn’t match Bethesda guidelines and who had results of hMLH1 methylation and BRAF mutations. Results: Among the 33 patients, hMLH1 promoter methylation was observed in 36.4% (n = 12), and was not significantly related with clinicopathologic variables, including MLH1 expression. BRAF mutations were observed in 33.3% of the patients (n = 11). Four of 11 and five of 22 patients with MSI-H colon cancers were BRAF mutation (+)/ hMLH1 promoter methylation (?) or BRAF mutation (?)/hMLH1 promoter methylation (+). Of the 33 patients, 21.2% were BRAF mutation (+)/hMLH1 promoter methylation (+), indicating sporadic cancers. Seventeen patients (51.5%) were BRAF mutation (?)/ hMLH1 promoter methylation (?), and suggested Lynch syndrome. Conclusion: Patients with MSI-H colorectal cancers not fulfilling the Bethesda guidelines possibly have hereditary colorectal cancers. Adding tests of hMLH1 promoter methylation and BRAF mutations can be useful to distinguish them from sporadic colorectal cancers.

유전성 비용종증 대장암 환자에서 발생한 4개의 동시성 다발성 대장암과 1개의 소장암

김민국(Min Kuk Kim),이원석(Won Suk Lee),박치민(Chi Min Park),윤성현(Seong Hyeon Yun),이우용(Woo Yong Lee),전호경(Ho Kyung Chun) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.72 No.6

The frequency of multiple synchronous carcinomas of the colon and rectum have varied in different reports from 3∼4% to more than 10% of all tumors of the large bowel. Especially, the frequency is higher in hereditary non-polyposis colorectal cancer (HNPCC) patients. There are a few reported cases of five simultaneous cancers in a patient at the same time. We report here on a case of five synchronous cancers arising from the terminal ileum and colon in a patient with a strong familial tendency for colon cancer. The patient was a 43-year-old-female who presented with intermittent abdominal pain and diarrhea for one month. Colonoscopic examination revealed four adenocarcinomas at the proximal ascending, the proximal transverse, the distal descending and the sigmoid colon; the cancer in the sigmoid colon was at 30 ㎝ above the anal verge. During the operation, another 3 ㎝ sized ulcerative lesion was noted at the terminal ileum. Total colectomy, including the lesion of the terminal ileum, and ileorectal anastomosis were performed. Histologic evaluation revealed that all those lesions were adenocarcinomas invading the pericolic fat and three out of 126 lymph nodes were invaded by the cancer cells. It was a MSI-high cancer; 5 markers of MSI (BAT25, BAT26, D5S346, D17S250 and D2S123) were all unstable. We revealed a point mutation of the 67th base (GaT) of the 1st exon of hMLH1.

유전자 불안정성의 기전과 임상적 적용

이석환 대한대장항문학회 2004 Annals of Coloproctolgy Vol.20 No.1

Knowledge of and Practice Patterns for Hereditary Colorectal Cancer Syndromes in Korean Surgical Residents

박장호,이수영,김덕우,강성범,정승용,박규주 대한대장항문학회 2013 Annals of Coloproctolgy Vol.29 No.5

Purpose: Obtaining a detailed family history through detailed pedigree is essential in recognizing hereditary colorectal cancer (CRC) syndromes. This study was performed to assess the current knowledge and practice patterns of surgery residents regarding familial risk of CRC. Methods: A questionnaire survey was performed to evaluate the knowledge and the level of recognition for analyses of family histories and hereditary CRC syndromes in 62 residents of the Department of Surgery, Seoul National University Hospital. The questionnaire consisted of 22 questions regarding practice patterns for, knowledge of, and resident education about hereditary CRC syndromes. Results: Two-thirds of the residents answered that family history should be investigated at the first interview, but only 37% of them actually obtained pedigree detailed family history at the very beginning in actual clinical practice. Three-quarters of the residents answered that the quality of family history they obtained was poor. Most of them could diagnose hereditary nonpolyposis colorectal cancer and recommend an appropriate colonoscopy surveillance schedule; however, only 19% knew that cancer surveillance guidelines differed according to the family history. Most of our residents lacked knowledge of cancer genetics, such as causative genes, and diagnostic methods, including microsatellite instability test, and indicated a desire and need for more education regarding hereditary cancer and genetic testing during residency. Conclusion: This study demonstrated that surgical residents’ knowledge of hereditary cancer was not sufficient and that the quality of the family histories obtained in current practice has to be improved. More information regarding hereditary cancer should be considered in education programs for surgery residents.