Hereditary Nonpolyposis Colorectal Cancer Syndrome Research Articles

Detecting microsatellite instability in colorectal cancer using Transformer-based colonoscopy image classification and retrieval.

Colorectal cancer (CRC) is a major global health concern, with microsatellite instability-high (MSI-H) being a defining characteristic of hereditary nonpolyposis colorectal cancer syndrome and affecting 15% of sporadic CRCs. Tumors with MSI-H have unique features and better prognosis compared to MSI-L and microsatellite stable (MSS) tumors. This study proposed establishing a MSI prediction model using more available and low-cost colonoscopy images instead of histopathology. The experiment utilized a database of 427 MSI-H and 1590 MSS colonoscopy images and vision Transformer (ViT) with different feature training approaches to establish the MSI prediction model. The accuracy of combining pre-trained ViT features was 84% with an area under the receiver operating characteristic curve of 0.86, which was better than that of DenseNet201 (80%, 0.80) in the experiment with support vector machine. The content-based image retrieval (CBIR) approach showed that ViT features can obtain a mean average precision of 0.81 compared to 0.79 of DenseNet201. ViT reduced the issues that occur in convolutional neural networks, including limited receptive field and gradient disappearance, and may be better at interpreting diagnostic information around tumors and surrounding tissues. By using CBIR, the presentation of similar images with the same MSI status would provide more convincing deep learning suggestions for clinical use.

Evaluation of the psychological state of patients suspected of Lynch syndrome after the germline genetic testing result.

e24201 Background: Lynch syndrome (LS) also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, is caused by a deficiency of Mismatch Repair Complex (MMR) enzymes. It is an autosomal dominant syndrome associated with an increased risk of developing colorectal cancer and other neoplasms, which can be confirmed using a germline molecular test. Psychological distress can be triggered regardless of the genetic test result. How the individual reacts emotionally and psychologically to the development can influence the processing of information and guidelines and adherence to preventive strategies. In this context, tracking anxiety symptoms provides opportunities for psychosocial follow-up planning. Objective: to evaluate levels of anxiety and depression in cancer patients suspected of having LS submitted to genetic testing. Methods: 84 patients with clinical criteria for LS were submitted to the germline genetic panel by NGS and immediately after the genetic test result, answered the Hospital Anxiety and Depression Scales (HADS). Data were expressed as mean±SD and compared using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS v20.0, p < 0.05). Results: The mean levels of anxiety (5.59±3.31) were significantly higher than that of depression (4.63±3.58) ( p= 0.007), both domains were positively correlated ( p< 0.001, r= 0.447). Eighteen patients (21.4%) had pathogenic mutations in genes of the MMR complex. A positive diagnosis did not affect levels of anxiety or depression (pathogenic variant p= 0.617 and p= 0.478; Significance Uncertain-VUS p= 0.415 and p= 0.561, respectively). Females had higher levels of depression than males ( p= 0.047, with a relative risk of 1.65 times; CI95% = 1.05-13.19); however, other clinical and therapeutic characteristics did not significantly influence anxiety levels or depression. Conclusions: Colorectal cancer women are most sensitive to depression after germline genetic testing, despite the results. These findings reinforce the need for psychological screening of individuals undergoing genetic testing for LS and continuing psychological follow-up after receiving the genetic test.

A common genetic variation in GZMB may associate with cancer risk in patients with Lynch syndrome.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is a common genetic predisposition to cancer due to germline mutations in genes affecting DNA mismatch repair. Due to mismatch repair deficiency, developing tumors are characterized by microsatellite instability (MSI-H), high frequency of expressed neoantigens and good clinical response to immune checkpoint inhibitors. Granzyme B (GrB) is the most abundant serine protease in the granules of cytotoxic T-cells and natural killer cells, mediating anti-tumor immunity. However, recent results confirm a diverse range of physiological functions of GrB including that in extracellular matrix remodelling, inflammation and fibrosis. In the present study, our aim was to investigate whether a frequent genetic variation of GZMB, the gene encoding GrB, constituted by three missense single nucleotide polymorphisms (rs2236338, rs11539752 and rs8192917) has any association with cancer risk in individuals with LS. In silico analysis and genotype calls from whole exome sequencing data in the Hungarian population confirmed that these SNPs are closely linked. Genotyping results of rs8192917 on a cohort of 145 individuals with LS demonstrated an association of the CC genotype with lower cancer risk. In silico prediction proposed likely GrB cleavage sites in a high proportion of shared neontigens in MSI-H tumors. Our results propose the CC genotype of rs8192917 as a potential disease-modifying genetic factor in LS.

Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry

Background: Endometrial cancer (EC) is known as the most common malignancy of the female reproductive system, suggested to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome (LS). Objectives: Therefore, the aim of the present study was to screen for LS in patients with EC using immunohistochemistry (IHC). Methods: In this retrospective cross-sectional study, the patients with EC, referred to Qaem Hospital, Mashhad, Iran, from 2015 - 2019, were enrolled. Paraffin-embedded tissue blocks were then examined via IHC for the expression of four mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6, and PMS2. The demographic and tumor-related data were also extracted from medical records and pathology reports. The data were consequently analyzed at the significance level of P < 0.05. Results: A total number of 100 patients with EC were evaluated using IHC, and 12 (12%) cases were found suspected. As well, no significant relationship was observed between LS and age, tumor site, tumor histology, tumor size, tumor grade, tumor-infiltrating lymphocytes (TILs), and a family/personal history of malignancies. Conclusions: The prevalence of LS based on the IHC expression of the MMR proteins (MLH1, MSH2, MSH6, and PMS2) was 12% in the patients with EC. There was also no significant relationship between the cases suspected and the demographic and tumor-related data.

Multiple Sebaceous Carcinomas in an African American Patient with Muir-Torre Syndrome

Sebaceous carcinoma is a rare, aggressive cutaneous tumor that is known to be associated with Muir-Torre syndrome, an autosomal dominant phenotypic variant of hereditary non-polyposis colorectal cancer or Lynch Syndrome. This case report describes a rare case of multiple sebaceous carcinomas on the back and groin in an African American male in the setting of Muir-Torre syndrome.

EP039: Does Lynch syndrome cause predisposition to breast cancer? Experience from a hereditary breast cancer clinic in Pakistan

Lynch Syndrome (LS), also known as hereditary non-polyposis colorectal cancer syndrome, is an autosomal dominant disorder caused by the presence of germline pathogenic (P) or likely pathogenic (LP) variants in DNA mismatch repair (MMR) genes, which include MLH1, MSH2, MSH6, PMS2, and EPCAM. Presence of a disease-causing variant in any of these MMR genes increases an individual’s lifetime risk of developing colorectal cancer (CRC) (61%), endometrial (57%), ovarian (38%), renal pelvis or ureter (28%), prostate (24%), breast (19%), small bowel (11%), gastric (9%), brain (8%), hepatobiliary cancer (4%) and pancreatic cancer (2%).

Genetic counselling unit- model and experience of University Hospital for Tumours in Croatia

Background: Genetic counselling unit exists as a separate functional unit in University hospital for tumours from the year 2015. It is based on cooperation and teamwork of experts of different profiles: medical geneticist, surgeons, oncologists, molecular geneticists, specialized nurses and psychologists. The aim is to recognize and counsel patients with family and personal history indicative of the hereditary cancer syndrome. Most of the patients are those suspected to have hereditary breast and ovarian cancer syndrome, although there are also patients with familial adenomatous polyposis, Lynch syndrome(hereditary non-polyposis colorectal cancer syndrome), neurofibromatosis and few other very rare hereditary cancer syndromes (e.g.

Co-Occurrence of Familial Non-Medullary Thyroid Cancer (FNMTC) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Associated Tumors-A Cohort Study.

Familial non-medullary thyroid cancer (FNMTC) is a form of endocrine malignancy exhibiting an autosomal dominant mode of inheritance with largely unknown germline molecular mechanism. Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is another hereditary autosomal dominant cancer syndrome which, if proven to be caused by germline mutations in mismatch repair genes (MMR)—MLHL, MSH2, MSH6, PMS2, and EPCAM—is called Lynch syndrome (LS). LS results in hereditary predisposition to a number of cancers, especially colorectal and endometrial cancers. Tumors in LS are characterized by microsatellite instability (MSI) and/or loss of MMR protein expression in immunohistochemistry (IHC). MSI is a rare event in thyroid cancer (TC), although it is known to occur in up to 2.5% of sporadic follicular TC cases. There are limited data on the role of germline MMR variants FNMTC. The goal of this study was to analyze the potential clinical and molecular association between HNPCC and FNMTC. We performed a cohort study analyzing the demographic, clinical, and pathologic data of 43 kindreds encompassing 383 participants (104 affected, 279 unaffected), aged 43.5 [7-99] years with FNMTC, and performed high-throughput whole-exome sequencing (WES) of peripheral blood DNA samples of selected 168 participants (54 affected by FNMTC and 114 unaffected). Total affected by thyroid cancer members per family ranged between 2 and 9 patients. FNMTC was more prevalent in women (68.3%) and characterized by a median tumor size of 1.0 [0.2-5.0] cm, multifocal growth in 44%, and gross extrathyroidal extension in 11.3%. Central neck lymph node metastases were found in 40.3% of patients at presentation, 12.9% presented with lateral neck lymph node metastases, and none had distant metastases. Family history screening revealed one Caucasian family meeting the clinical criteria for FNMTC and HNPCC, with five members affected by FNMTC and at least eight individuals reportedly unaffected by HNPCC-associated tumors. In addition, two family members were affected by melanoma. Genome Analysis Tool Kit (GATK) pipeline was used in variant analysis. Among 168 sequenced participants, a heterozygous missense variant in the MSH2 gene (rs373226409; c.2120G>A; p.Cys707Tyr) was detected exclusively in FNMTC- HNPCC- kindred. In this family, the sequencing was performed in one member affected by FNMTC, HPNCC-associated tumors and melanoma, one member affected solely by HNPCC-associated tumor, and one member with FNMTC only, as well as seven unaffected family members. The variant was present in all three affected adults, and in two unaffected children of the affected member, under the age of 18 years, and was absent in non-affected adults. This variant is predicted to be damaging/pathogenic in 17/20 in-silico models. However, immunostaining performed on the thyroid tumor tissue of two affected by FNMTC family members revealed intact nuclear expression of MSH2, and microsatellite stable status in both tumors that were tested. Although the MSH2 p.Cys707Tyr variant is rare with a minor allele frequency (MAF) of 0.00006 in Caucasians; it is more common in the South Asian population at 0.003 MAF. Therefore, the MSH2 variant observed in this family is unlikely to be an etiologic factor of thyroid cancer and a common genetic association between FNMTC and HNPCC has not yet been identified. This is the first report known to us on the co-occurrence of FNMTC and HNPCC. The co-occurrence of FNMTC and HNPCC-associated tumors is a rare event and although presented in a single family in our large FNMTC cohort, a common genetic background between the two comorbidities could not be established.

Spectrum of mutations in genes associated with familial colorectal cancer syndrome (MLH1, MSH2, PMS2, MSH6, and APC): A not so common hereditary cancer syndrome in Indian population.

Incidence of colorectal cancer (CRC) is lower in India than in other parts of the world. Approximately 5% to 10% of CRC is inherited. Hereditary non-polyposis colorectal cancer (HNPCC) syndrome and familial adenomatous polyposis (FAP) syndrome are the two known familial cancer syndromes of gastrointestinal tract, which occur due to inherited genetic predisposition. Not much is known about the molecular profile of families with inherited CRC syndromes seen in Indian population. At our institute, we have been providing genetic testing and counseling service to all the families referred to us with suspicion of inherited cancer predisposition syndrome. We analyzed 36 suspected families at our clinic. Personal and family history of cancer was obtained from the proband and appropriate genetic testing was performed in 19 patients (13 with HNPCC, 5 with FAP, and 1 with Cowden syndrome). We present here our experience and spectrum of pathogenic variants observed in this patient cohort and review on published studies describing molecular profile of Indian patients with CRC syndromes.

Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition.

Hereditary predisposition to cancer concerns between 5% and 10% of cancers. The main genes involved in the most frequent syndromes (hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome) were identified in the 1990s. Exploration of their functional pathways then identified novel genes for hereditary predisposition to cancer, and candidate genes whose involvement remains unclear. To determine the contribution of truncating variants in 11 candidate genes (BARD1, FAM175A, FANCM, MLH3, MRE11A, PMS1, RAD50, RAD51, RAD51B, RINT1, and XRCC2) to cancer predisposition in a population of interest, panel sequencing was performed in 849 patients with a suspected hereditary predisposition to cancer for whom a diagnostic panel of 38 genes identified no causal mutation. Sixteen truncating variants were found in FANCM (n = 7), RINT1 (n = 4), RAD50 (n = 2), BARD1, PMS1, and RAD51B. FANCM (adjusted P‐value: .03) and RINT1 (adjusted P‐value: .04) were significantly associated with hereditary breast and ovarian cancer. However, further studies are required to determinate the risk of cancer, including the segregation of the variants in the families of our cases. No mutation was identified in RAD51, MRE11A, FAM175A, XRCC2, or MLH3. The involvement of these genes in the hereditary predisposition to cancer cannot be ruled out, although if it exists it is rare or does not seem to involve truncating variants.

How to improve the identification of patients with cancer eligible for genetic counselling?

International guidelines recommend genetic counselling and if indicated the genetic testing for treatment, disease prevention and follow-up for patients and their relatives. However, there is limited utilisation of genetic counselling. This study aimed to verify whether anindividual semi-structured guideline-based interview improves the identification of patients eligible for geneticcounselling. Unselected patients with cancer were interviewed. A dedicated nurse provided an ad-hoc guideline-based questionnaire to assess the presence of criteria for a possible hereditary breast and ovarian cancer syndrome or hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). The interest of patients to undergo genetic counselling was also investigated. Ninety patients were enrolled in the study; 20 (22.2%) of these had already undergone genetic counselling. The interview identified 23 (32.8%) of the remaining 70 patients that were eligible for genetic counselling. Two-third of the patients (n=59) were interested in genetic counselling irrespective of socio-demographic factors or cancer type. A logistic regression analysis for age, gender, parental status, educational level and cancer type did not reveal any independent factor that was associated with patients who had previous genetic counselling. Our preliminary findings suggest that a semi-structured guideline-based interview can substantially improve the identification of patients eligible for genetic counselling.

High predictability for identifying Lynch syndrome via microsatellite instability testing or immunohistochemistry in all Lynch-associated tumor types.

Lynch syndrome is an inherited cancer-prone syndrome identified in ~3% of all colorectal cancer (CRC) patients and ~2% of all endometrial cancer (EC) patients (1-3). It is defined by identification of a germline mutation in one of the DNA mismatch repair (MMR) genes ( MSH2, MLH1, MSH6, PMS2, EPCAM ) whose proteins function to maintain replication fidelity of DNA prior to mitosis, and sets it apart from other hereditary non-polyposis colorectal cancer (HNPCC) syndromes such as Familial Colorectal Cancer Type X and Polymerase Proofreading Polyposis syndrome (3).

Whole-exome sequencing identified a novel mutation of MLH1 in an extended family with lynch syndrome

Hereditary nonpolyposis colorectal cancer or Lynch syndrome is autosomal dominant cancer predisposition syndrome characterized by early onset of colorectal cancer and neoplasia in other organs. This condition typically caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. To date, a considerable number of MLH1 gene mutations have been found to be associated with Lynch syndrome. We were aimed at identifying a genetic mutation in an extended Iranian family affected by Lynch syndrome-related cancers. Here, we applied whole-exome sequencing to identifying mutation in the proband. Furthermore, we applied Sanger sequencing to validate the candidate variant. We found a heterozygous novel single nucleotide deletion (c.206delG) in the exon two of the MLH1 gene in the proband. Also, Sanger sequencing analysis showed that this mutation has segregated in all affected family members. The mutation (c.206delG:p.R69fs) may create a premature stop codon followed by the formation of a truncated (p.R69fs) Mlh1 protein. Our findings expand the mutational spectra of MLH1 gene related Lynch syndrome which is vital for screening and genetic diagnosis of the disease.

Signet Ring Cell Carcinoma of the Stomach Presenting With Gastric Outlet Obstruction

30 year old male with no significant past history came to the emergency room with 2 week history of abdominal pain,dark brown emesis, early satiety and unable to keep food down.Family history was significant for maternal grandmother who died of colon cancer at age 49.Physical exam was unremarkable except for HR 120 beats per minute. Blood work including a complete blood count and comprehensive metabolic profile were normal.An esophagogastroduodenoscopy showed LA Grade-D esophagitis in the lower thirds of esophagus with contact oozing and massive amount of coffee ground material in stomach. Further suctioning of the gastric contents revealed a cratered necrotic ulcer in the prepyloric region with pyloric distortion precluding duodenal intubation,consistent with gastric outlet obstruction.Gastric biopsies of the ulcer showed poorly differentiated adenocarcinoma with microscopic sections showing >80% signet-ring cells. Further staging with abdominal-pelvic Computed Tomography and laparoscopic staging of the gastric cancer was T3N3aM0. Patient ultimately had a Subtotal gastrectomy with Billroth II with lymphadenectomy. After discharge patient was referred to tertiary center for further enrollment in clinical trials. Gastric cancer is the third most common cause of cancer death worldwide.Signet Ring cell cancer (SRCC) is a poorly differentiated adenocarcinoma characterized by the malignant cells in which the nucleus is pressed to one side by the presence of intracytoplasmic mucus. While the incidence of gastric cancer has been declining with effective treatment of H.pylori,the rising incidence of SRCC indicates that H.pylori infection is not a significant risk factor for SRCC. SRCC has been described in association with hereditary diffuse gastric cancer due to germline mutation in CDH1 resulting in tumor cells proliferation .It has also been a part of Hereditary non-polyposis colorectal cancer and gastrointestinal polyposis syndromes as a result of mutations in APC genes. Our case highlights a rare aggressive histological subtype of gastric cancers.2664_A Figure 1. Endoscopy findings2664_B Figure 2. Black arrow showing normal glandular structure of stomach and red arrow showing cancerous tissue2664_C Figure 3. Black arrow showing Signet ring cell

Value of EGD for gastric cancer surveillance in patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome (LS).

1522Background: Gastric cancer (GC) is the second most common non-gynecologic malignancy in patients with LS. Due to an absence of prospective randomized data, the value of esophago-gastro-duodenos...

MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries.

Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.

Prevalence and characteristics of hereditary non-polyposis colorectal cancer (HNPCC) syndrome in immigrant Asian colorectal cancer patients

BackgroundThe prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. A non-hereditary, acquired process of hypermethylation of the MLH1 promoter can also lead to silencing of MLH1 protein expression. Diagnosis of HNPCC in patients with colorectal and other related cancers is important in the clinical treatment and surveillance of related cancers. The prevalence and clinical characteristics of HNPCC in Asian colorectal cancer patients has been reported in small studies and unique features have been suggested.MethodsWe retrospectively reviewed the clinical characteristics of Asian patients who were diagnosed of colon cancer between 1/2002 and 6/2015, and performed IHC for four MMR protein expressions on tumor specimens as a screening test for HNPCC, followed by confirmatory tests of genomic sequencing and hypermethylation analysis.ResultsOne hundred forty-three patients were identified. Thirty-one patients were diagnosed younger than 50 years old, while 112 patients were diagnosed older than 50 years old. Six cases of HNPCC were found with a prevalence of 4.19%. The prevalence in the group of patients diagnosed younger than 50 years old is 16.1%, and that in patients diagnosed older than 50 years old is 0.89%. All patients with HNPCC had family histories of colon or gastric cancer. Tumor locations in the HNPCC patients were predominantly in the descending or sigmoid colon (67%). Half of the HNPCC patients had MSH6 mutations. Hypermethylation of the MLH1 gene was only present in 2.80% of the patients.ConclusionThe prevalence of HNPCC is high in patients younger than 50 years old and extremely low in those older than 50 years old. These results may be useful in the future development of guidelines for HNPCC laboratory screening among Asian patients. The pathological and clinical features of HNPCC in this group of Asian immigrant patients are more similar to those reported on Asian patients in their home countries than to Caucasian patients in Western countries, and will warrant further large-scale evaluation.

Metachronous Bilateral Urothelial Carcinoma in a Patient with Hereditary Nonpolyposis Colorectal Cancer Syndrome - A Case Report

Metachronous Bilateral Urothelial Carcinoma in a Patient with Hereditary Nonpolyposis Colorectal Cancer Syndrome - A Case Report

Genetic counseling for hereditary cancer

This paper provides an overview of the current approach to genetic counseling for cancer, using hereditary nonpolyposis colorectal cancer (HNPCC) as a prototype. Heretofore, when evaluating the possibility of an HNPCC diagnosis, physicians had to rely exclusively on a detailed family history of cancer in the context of an extended pedigree. Patients in the direct genetic lineage who had one or more first-degree relatives with an HNPCC syndrome cancer were told that they had a 50% likelihood of inheriting the deleterious gene. However, with the discovery of the HNPCC genes (hMSH2, hMLH1, hPMS1, hPMS2), genetic counseling can now provide a more precise determination of a patient's lifetime cancer destiny. Since these DNA findings are new, guidelines for sharing this information with patients remain preliminary. One must be certain that the patient wants to receive DNA information and that he or she is aware of potential discrimination by insurance companies and employers, as well as the possibility of psychological sequelae.