Cancer In Hereditary Nonpolyposis Colorectal Cancer Research Articles

Rectal Cancer in Patients with Hereditary Nonpolyposis Colorectal Cancer Compared with Sporadic Cases: Response to Neoadjuvant Chemoradiation and Local Recurrence.

This study aimed to assess the effect of neoadjuvant chemoradiation (nCXRT) on tumor regression and oncologic outcome of middle and low rectal cancer in patients of hereditary nonpolyposis colorectal cancer (HNPCC) compared to sporadic cases. This was a retrospective cohort study that compared the outcomes of patients with HNPCC presenting with middle or low rectal cancer indicated for nCXRT vs patients with sporadic rectal cancer. All patients received long-course nCXRT followed by total mesorectal excision. Primary outcome was pathologic tumor regression grade (TRG) assessed after resection. Secondary outcomes included disease-free survival and overall survival. Fifty-eight patients with HNPCC (24 female) were included in the study matched with 58 patients with sporadic rectal cancer (out of 166 using propensity score matching). Patients with HNPCC and sporadic rectal cancer were matched regarding tumor pathology TNM stage and lymphovascular invasion. In the HNPCC group, 36 patients (62%) had tumor regression (TRG3 = 6 (10.3%); TRG2 = 12 (20.6%); TRG1 = 18 (31%)) compared to 52 patients (92%) who had tumor regression in the control group (TRG4 = 9; TRG3 = 15; TRG2 = 18; TRG1 = 10) (p < 0.0007). After a median follow-up of 48 months, survival analysis revealed higher local recurrence and lower overall survival in patients with HNPCC compared to patients with sporadic rectal cancer. Rectal cancer in patients with HNPCC showed poorer response to nCXRT and was followed by higher local recurrence and lower overall survival than patients with sporadic rectal cancer. Tumor regression was detected in <65% of patients with HNPCC compared to >90% of patients with sporadic rectal cancer, and none of patients with HNPCC had a complete response.

P33. NK-92 cellular immunotherapy as an alternative to donor derived peripheral blood NK cells

<h3>INTRODUCTION</h3> Hypermethylation of the promoter region of the <i>hMLH1</i> gene is associated with absent expression of MLH1 protein in sporadic colorectal cancers with microsatellite instability (MSI+), and it has been proposed that methylation may be a mechanism of inactivation in Knudson9s hypothesis. The incidence of hypermethylation of the<i>hMLH1</i> promoter in hereditary non-polyposis colorectal cancer (HNPCC) versus MSI+ sporadic colorectal cancer was investigated and compared. <h3>METHODS</h3> DNA was available from 10 HNPCC colorectal cancers (median age 58 years, range 39-67) with germline mutations in <i>hMLH1 </i>and 10 MSI+ sporadic colorectal cancers (mean age 79 years, range 41-85). MSI was determined by amplification of BAT26 and TGF-β RII. The methylation status of the <i>hMLH1</i> promoter was studied by the polymerase chain reaction (PCR) based<i>Hpa</i>II restriction enzyme assay technique. Evidence of allelic loss at <i>hMLH1 </i>was searched for in the HNPCC colorectal cancers. <h3>RESULTS</h3> All cases were confirmed to be MSI+. The promoter region of <i>hMLH1 </i>was hypermethylated in seven of 10 MSI+ sporadic cancers versus 0 of 10 HNPCC cancers (p&lt;0.002). Evidence of loss of heterozygosity at<i>hMLH1 </i>was observed in eight of the 10 HNPCC colorectal cancers. <h3>CONCLUSION</h3> While mutations and allelic loss are responsible for the MSI+ phenotype in HNPCC cancers, the majority of MSI+ sporadic cancers are hypermethylated in the promoter region of <i>hMLH1.</i> These data further support our argument that tumours from HNPCC patients, which almost always acquire a raised mutation rate, mostly follow a different pathway from MSI+ sporadic tumours.

Risk of Colonic Neoplasia After Proctectomy for Rectal Cancer in Hereditary Nonpolyposis Colorectal Cancer

To define the neoplastic risk in the remaining colon after proctectomy for rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC). The extent of surgery for rectal cancer in HNPCC is controversial. In determining which operation to perform, surgeons and patients must consider cancer risk in the remaining colon as well as functional consequences of removing the entire colorectum. The natural history of colon neoplasia in this situation is understudied and is not well-defined. A single-institution hereditary colorectal cancer database was queried for patients meeting Amsterdam criteria and with rectal cancer. Patient demographics, surgical management, and follow-up were recorded. Fifty HNPCC patients with a primary diagnosis of rectal cancer treated by proctectcomy were included. Detailed follow-up colonoscopy data were available for 33 patients. Forty-eight high-risk adenomas developed in 13 patients (39.4%). Five patients (15.2%) developed metachronous adenocarcinoma at a median of 6 years (range 3.5-16) after proctectomy, including 3 at advanced stage. One of these patients developed a high-risk adenoma before cancer. Mean interval between the last normal colonoscopy and cancer discovery was 42 months (range 23.8-62.1) with one developing within 2 years. Thus, 17 of 33 patients (51.5%) developed high-risk adenoma or cancer after proctectomy. Surgeons and patients need to be aware of substantial risk for metachronous neoplasia after proctectomy. Selection of operation should be individualized, but total proctocolectomy and ileoanal pouch should be strongly considered. If patients undergo proctectomy alone, close surveillance is mandatory.

Endoscopic and Surgical Management of Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is a disease characterized by autosomal dominant clustering of colorectal cancer (CRC) as well as other cancers. It is critical for clinicians and surgeons caring for patients with HNPCC to be familiar with their management related to CRC. Based on retrospective studies, screening colonoscopy is recommended every 1 to 2 years beginning at age 20 to 25, or 10 years younger than the earliest CRC in the family (whichever is earlier). HNPCC patients with colon cancer should be considered for total abdominal colectomy rather than a more limited segmental colon resection due to the increased risk of metachronous neoplasia associated with the condition. Rectal cancer in HNPCC has not been well studied, but discussions with the patient regarding surgical management should weigh the risks of metachronous CRC with the morbidity and quality of life issues associated with proctocolectomy. Regardless of the procedure, a patient with HNPCC requires close postoperative endoscopic surveillance of any remaining at-risk mucosa. In terms of chemoprevention, aspirin has been shown to be effective in preventing colorectal neoplasia in prospective trials and should be considered in patients who do not have a contraindication to the drug. Trials for other chemopreventative agents in HNPCC are ongoing. As more is learned about particular genotype-phenotype correlations with Lynch syndrome, this will likely affect surgical decision making. Despite all of these efforts in the management of patients with HNPCC or Lynch syndrome, incident CRCs still occur, thus reinforcing the need for further studies to better understand the optimal management of these patients.

Surgery for colonic cancer in HNPCC: total vs segmental colectomy

The high reported risk of metachronous colon cancer (MCC) in hereditary nonpolyposis colorectal cancer (HNPCC) has led some authors to recommend total colectomy (TC) as the preferred operation for primary colon cancer, but this remains controversial. No previous study has compared survival after TC with segmental colectomy (SC) in HNPCC. The aim of this study was to determine the risk of developing MCC in patients with genetically proven HNPCC after SC or TC for cancer, and to compare their long-term survival. This is a prospective cohort study of all patients referred to our unit between 1995 and 2009 with a proven germline mismatch repair gene defect, who had undergone a resection for adenocarcinoma of the colon with curative intent. All patients were offered annual endoscopic surveillance. Of 60 patients in the study, 39 had TC as their initial surgery and 21 had SC. After 6 years follow up, MCC occurred in eight (21%) SC patients and in none of the TC patients (P = 0.048). The risk of developing MCC after SC was 20% at 5 years. Colorectal cancer-specific survival was better in TC patients (P = 0.048) but overall survival of the two groups was similar (P = 0.29). Patients with HNPCC have a significant risk of MCC after SC. This is eliminated by performing TC as the primary operation for colonic cancer.

The community uptake of an online CRC risk assessment and its utility to assess for a potential hereditary colon cancer syndrome

Purpose The identification of individuals with Hereditary Non Polyposis Colorectal Cancer (HNPCC) in the population is suboptimal. Causes include lack of physician recognition or failure to take an accurate family history. While colorectal cancer (CRC) in HNPCC is preventable by annual colonoscopy it is underutilized in part by lack of physician recommendation or poor understanding of personal risk of disease. We developed an online CRC risk assessment (http://www.clevelandclinic.org/score) incorporating family and personal history of adenomas and CRC which generated a pedigree, risk category and screening recommendations based on ACG guidelines. Modifiable lifestyle factors were also assessed and personalized recommendations were provided to minimize neoplasia due to those factors. We assessed the feasibility and online uptake of this tool and determined the proportion of high risk individuals who meet criteria suspicious for HNPCC. Methods The assessment included questions on demographics, use of previous CRC screening, and family and personal history of adenomas and CRC in 3 generations. Height, weight, age > or < 50, race, smoking exposure, physical activity, and dietary habits assessed. Risk categories included average, low, medium, and high.

The Characteristics of Hereditary Colorectal Cancer Syndromes by Population Screening

The Characteristics of Hereditary Colorectal Cancer Syndromes by Population Screening Introduction. Colorectal cancer is important medical problem due to frequent occurrence and serious prognosis. Recent advances help to understand the role of heredity of colorectal carcinogenesis with possible implications for prevention. Aim of the Study. Is to characterise hereditary colorectal cancer by population screening in order to evaluate the needs and possibilities of prevention. Materials and methods. Population screening was performed in Valka district, evaluating the family cancer history by questionnaire. Hereditary colorectal cancer syndromes were diagnosed by internationally accepted clinical criteria. Results. The following population frequencies were identified: hereditary non-polyposis colorectal cancer (HNPCC), 0.059% (95% CI = 0.033-0.106%); suspected HNPCC and familial colorectal cancer, 0.107% (95% CI = 0.069-0.166%). The cancer burden among blood relatives of the affected families ranged 15.5-30.1%. The mean age of colorectal cancer diagnostics was 53.7-72.0 years. The probands were mostly oncologically healthy and up to 81.8% - below 50 years of age. Conclusions. The population frequencies of hereditary colorectal cancer syndromes correspond to significant number of cases. The high cancer burden among blood relatives of the affected families necessitates surveillance, and the age structure and health status of probands is well-suited for this.

Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition caused by inactivating mutations of DNA mismatch repair (MMR) genes. An accurate estimation of colorectal cancer risk for mutation carriers is essential for counselling and rationalizing screening programmes. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of all relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with an HNPCC spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. The cumulative lifetime risk was calculated by Kaplan-Meier analysis. Three hundred and forty-one colorectal cancers in 839 proven, obligate, or assumed mutation carriers were analysed. The cumulative risk to age 70 years for all mutation carriers combined was 50.4% (95% CI 47.8-52.9). The cumulative risk in males was 54.3% (95% CI 50.7-57.8), which was significantly higher than in females (log rank p = 0.02) who had a risk of 46.3% (95% CI 42.8-49.9). These penetrance estimates from HNPCC families attending high-risk clinics have been corrected for ascertainment bias and are appropriate risks for those referred to a high-risk clinic. Current colonoscopic screening guidelines are appropriate.

Identification of Differentially Expressed Genes in Microsatellite Stable HNPCC and Sporadic Colon Cancer

Some sporadic colon cancers and hereditary nonpolyposis colorectal cancer (HNPCC) have been known by a constitutional defect in mismatch gene repair (MMR) and dysfunction in of this MMR system, which lead to an aberrant phenotype that can cause microsatellite instability. However, the clinicopathologic features of still existing microsatellite stable (MSS) colon cancer remain to be investigated. We compared the gene expression patterns of nine tumor tissues of HNPCC and nine tumor tissues of sporadic colon cancer with their adjacent pathologically normal, MSS tissues by modified differential display-polymerase chain reaction, selected four potential marker genes, and confirmed their reproducibility by reverse transcriptase-polymerase chain reaction. Reg I, MLCK, and MYH11 in tumors of MSS HNPCC showed significant differences in gene expression pattern compared with the adjacent pathologically normal tissues (P = 0.028, P = 0.002, and P = 0.001, respectively). Similar differences in expression patterns for the same set of genes were seen between the sporadic colon cancer group and their adjacent pathologically normal tissues (P = 0.012, P = 0.003, and P = 0.002, respectively). We suggest that the three cancer-associated differentially expressed genes in MSS sporadic colon cancer or MSS HNPCC might be potential tumor markers.

Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer–like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression

Women in hereditary nonpolyposis colorectal cancer (HNPCC) families have up to a 71% lifetime risk for developing endometrial cancer (EC). This compares to the female lifetime risk for colorectal cancer (CRC) in HNPCC of 60%. The basis of HNPCC is an inherited mutation in a mismatch repair gene (MMR). Aspirin and COX2 inhibitors seem to have a chemoprotective effect on CRC in the general population and are the subject of prospective clinical studies in patients at high risk for CRC including HNPCC. There is no evidence that these agents have any protective effect against EC in the general population. This study investigated the effect of aspirin and a COX2 inhibitor (rofecoxib) on an HNPCC EC cell line model (Ishikawa) by assessing the effect on proliferation, apoptosis, the cell cycle, and MMR gene expression. Aspirin inhibits EC cell proliferation by inducing apoptosis and changes in the cell cycle. This effect is not mediated by changes in MMR gene (hMSH2) expression as assessed by quantitative reverse transcription-polymerase chain reaction. Rofecoxib inhibits EC cell proliferation; this did not appear to be mediated by induction of apoptosis, by alterations of the cell cycle, or by changes in MMR gene expression.

Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer...

Gynäkologische Betreuung von Patientinnen mit HNPCC-Syndrom und deren Familien

Female patients with diagnosis of endometrial or ovarian cancer before the age of 45 are suspicious of hereditary non-polyposis colorectal cancer (HNPCC). In the daily routine it is difficult to distinguish between HNPCC and sporadic cancer, however, the consequences are severe. A standardised interview was conducted to evaluate the management of HNPCC-patients in medical practice. COHORT AND METHODS: 36 gynecologists working in medical practice were interviewed, statistical analyses were performed with SPSS 12.0. Most of the gynecologists refer to a hereditary tumor syndrome in consideration of family history, diagnosis at early age and synchronous or metachronous cancer. Patients with endometrial or ovarian cancer before the age of 45 years were rated as high risk patients. 72 % of the gynecologists take care of female patients suspicious of HNPCC according to the Bethesda criteria, even though half of these do not consider that diagnosis. Gynecological surveillance examinations are not fully taken into account. The interdisciplinary surveillance concept is rarely initiated. The current surveillance recommendation for patients suspicious of HNPCC should be applied more often in the daily routine of gynecological outpatient management. Sponsored by Deutsche Krebshilfe.

Psychological distress in women at risk of hereditary breast/ovarian or HNPCC cancers in the absence of demonstrated mutations

To examine psychological distress in women at risk of familial breast-ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC) with absence of demonstrated mutations in the family (unknown mutation). Two-hundred and fifty three consecutive women at risk of FBOC and 77 at risk of HNPCC and with no present or past history of cancer. They were aware of their risk and had received genetic counseling. Comparisons were made between these two groups, normal controls, and women who were identified to be BRCA1 mutation carriers. The questionnaires Beck Hopelessness Scale (BHS), General Health Questionnaire (GHQ-28), Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were employed to assess psychological distress. No significant differences concerning psychological distress were observed between women with FBOC and women with HNPCC. Compared to mutation carriers for BRCA1, the level of anxiety and depression was significantly higher in the FBOC group with absence of demonstrated mutation. Compared to normal controls, the level of anxiety was higher, while the level of depression was lower in the groups with unknown mutation. Women in the absence of demonstrated mutations have higher anxiety and depression levels than women with known mutation-carrier status. Access to genetic testing may be of psychologically benefit to women at risk for FBOC or HNPCC.

Colorectal cancer at a young age

Colorectal cancer at a young age

Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients.

MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH germline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP). A total of 20 APC-negative Korean FAP patients were analyzed for OGG1, MYH and MTH1 germline mutations. A total of 19 hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246 sporadic colorectal cancer cases were investigated for OGG1 and MYH mutations. A total of 14 R154H OGG1 polymorphisms were identified in hereditary, sporadic colorectal cancers, and normal controls. For the case-control analysis of OGG1 R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. R154H was a rare polymorphism associated with sporadic colorectal cancer patents (OR: 3.586, P= 0.053). R154H does not segregate with cancer phenotypes. Upon examining the possibility of recessive inheritance of R154H, we could not identify any complementary mutations in OGG1, MYH or MTH1. Samples with R154H were further screened for mutations of K-ras, beta-catenin, APC, p53, BRAF and the microsatellite instability (MSI) status. Eight somatic mutations were identified in these genes and G:C to T:A transversion mutations were not dominant in samples harboring R154H. This result raises the possibility that OGG1 R154H may function as a low/moderate-penetrance modifier for colorectal cancer development.

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer (CRC). The disease carries a >80% lifetime risk of CRC (mean age at diagnosis being 46 years). The CRCs that arise in HNPCC are usually right-sided and associated with synchronous and metachronous tumors. HNPCC is also associated with a high risk of extracolonic cancers, predominantly endometrial cancer. Predisposition to cancer in HNPCC has been attributed to mutations in mismatch repair (MMR) genes, over 95% of the identified mutations in HNPCC being in hMSH2 , hMLH1 , and hMSH6 . The abnormal MMR genes lead to instabilities in nucleotide repeat sequences (microsatellites) within the genome (MSI, microsatellite instability) that may lead to tumorigenesis and concerning pathologic features but improved clinical outcomes when compared with sporadic CRCs without MSI. Mutations in MMR genes are also associated with a host of other extraintestinal cancers. Each individual MMR gene has its own genotype-phenotype pattern of expression that can vary from individual to individual. As a result, this genetic information can be used to direct surveillance of affected and at-risk family members. Once the clinical criteria for HNPCC have been met and/or a gene mutation confirmed, affected patients show improved survival with cancer screenings every 1 to 2 years starting before age 25 years. Prophylactic colectomy for asymptomatic gene mutation carriers and the extent of colectomy when polyps or cancer arise in HNPCC remain the subject of debate. This issue will discuss our current understanding of the genetics of HNPCC, the various phenotypic expressions, genetic testing, surveillance, and current recommendations of management of this familial cancer syndrome.

Association of HNPCC and endometrial cancers.

Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

More Differences Between HNPCC-related and Sporadic Carcinomas From the Endometrium as Compared to the Colon

Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial carcinoma from sporadic carcinoma by histologic features as compared with colonic cases. Case-control study. From the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6) endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC-related tumor, 2 sporadic control cases were included. The tumors were evaluated for the following 7 pathologic features: tumor differentiation, T-stage, growth pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation, presence of lymphangioinvasive growth, and the amount of tumor-infiltrating lymphocytes. HNPCC-related endometrial carcinomas were significantly more often poorly differentiated (83% versus 27%), more often showed the presence of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more often present (100% versus 36%) compared with sporadic endometrial carcinomas. The differences between HNPCC and sporadic colorectal cancer specimens were less discriminating. HNPCC-related endometrial carcinomas are characterized by poor differentiation, more frequent Crohn-like lymphoid reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes. These features therefore might form the basis for selecting patients for counseling in a hereditary cancer clinic or testing for microsatellite instability or mutation analysis of mismatch repair genes, especially when they are of relatively young age.

Colorectal Pretumor Progression Before and After Loss of DNA Mismatch Repair

A pretumor progression model predicts many oncogenic cancer mutations may first accumulate in normal appearing colon. Although direct observations of early pretumor mutations are impractical, it may be possible to retrospectively reconstruct tumor histories from contemporary cancer mutations. To infer when and in what order mutations occur during occult pretumor progression, we examined 14 cancers from individuals with heterozygous germline mutations in DNA mismatch repair (MMR) genes or hereditary nonpolyposis colorectal cancer (HNPCC). Somatic inactivation of the normal allele occurs sometime during a lifetime and results in loss of MMR, elevated mutation rates, and subsequent widespread somatic microsatellite mutations in HNPCC cancers. Patient ages at MMR loss can be estimated because intervals between MMR loss and cancer removal can be inferred from numbers of microsatellite tumor mutations. The relative order of MMR loss during pretumor progression may also be inferred from its collective ages of occurrence. Somatic MMR loss preceded cancer removal by an average of 6.1 years, occurred relatively late in life (average of 41.6 versus 47.7 years at cancer removal), and was a surprisingly late (fifth or sixth) step. Calculations indicate five or six oncogenic mutations could accumulate with relatively normal replication fidelity in normal appearing colon. HNPCC pretumor progression essentially begins from birth and ends with MMR loss, implying elevated mutation rates and tumorigenesis may be unnecessary for most progression.

Hereditary nonpolyposis colorectal cancer: preventive management

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer. Inherited mutations in the mismatch repair genes associated with this syndrome have an approximate 80% lifetime risk of colorectal cancer. Since there are no premonitory signs of susceptibility to HNPCC, family history is the initial method for identifying those at increased risk. At risk individuals should undergo genetic counseling and testing. Although an algorithmic indication for genetic testing in at risk HNPCC patients is yet to be determined, many advocate initial screening for microsatellite instability (MSI) of the cancer specimen in individuals suspected of carrying HNPCC mutations. Those who test positive for MSI can then undergo further testing for mutations in the associated germline mismatch repair genes. Techniques for detecting these mutations currently include in vitro synthesized-protein assay, single-strand conformational polymorphism, and DNA sequencing. Given the aggressive nature of HNPCC adenomas, individuals who test positive for HNPCC mutations are recommended to undergo yearly colonoscopic surveillance starting at the age of 25. A reasonable alternative to lifetime colonoscopic surveillance for the prevention of colorectal cancer in these individuals is prophylactic colectomy. The prevention of colorectal cancer through pharmacological means is under investigation as another option in the management of HNPCC patients. Specifically, chemoprevention trials are currently ongoing to evaluate the efficacy of COX-2 inhibitors in the prevention of colorectal cancer in HNPCC and familial adenomatous polyposis patients.