Original Article
Clinical Findings with Implications for Genetic Testing in Families with Clustering of Colorectal Cancer
N Engl J Med 1998; 339:511-518August 20, 1998
- Abstract
Background
Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6 ) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evaluated whether clinical findings can predict the outcome of genetic testing.
Methods
We used denaturing gradient gel electrophoresis to identify MSH2 and MLH1 mutations in 184 kindreds with familial clustering of colorectal cancer or other cancers associated with hereditary nonpolyposis colorectal cancer. Information on the site of cancer, the age at diagnosis, and the number of affected family members was obtained from all families.
Results
Mutations of MSH2 or MLH1 were found in 47 of the 184 kindreds (26 percent). Clinical factors associated with these mutations were early age at diagnosis of colorectal cancer, the occurrence in the kindred of endometrial cancer or tumors of the small intestine, a higher number of family members with colorectal or endometrial cancer, the presence of multiple colorectal cancers or both colorectal and endometrial cancers in a single family member, and fulfillment of the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer (at least three family members in two or more successive generations must have colorectal cancer, one of whom is a first-degree relative of the other two; cancer must be diagnosed before the age of 50 in at least one family member; and familial adenomatous polyposis must be ruled out). Multivariate analysis showed that a younger age at diagnosis of colorectal cancer, fulfillment of the Amsterdam criteria, and the presence of endometrial cancer in the kindred were independent predictors of germ-line mutations of MSH2 or MLH1. These results were used to devise a logistic model for estimating the likelihood of a mutation in MSH2 and MLH1.
Conclusions
Assessment of clinical findings can improve the rate of detection of mutations of DNA mismatch-repair genes in families suspected of having hereditary nonpolyposis colorectal cancer.
Media in This Article
Figure 2
Strategy of Molecular Analysis in Families Suspected of Having Hereditary Nonpolyposis Colorectal Cancer.Figure 1
Estimated Probability of a Deleterious MSH2 or MLH1 Mutation as a Function of the Mean Age at Diagnosis of Colorectal Cancer within a Family and Whether the Amsterdam Criteria Were Met in Families with No Members with Endometrial Cancer (Panel A) and in Families with at Least One Member with Endometrial Cancer (Panel B).Article Activity
- Article
The lifetime risk of colorectal cancer among whites in the Western world is approximately 4 percent. The cause of colorectal cancer is multifactorial, involving hereditary susceptibility, environmental factors, and somatic genetic changes during tumor progression.1 A family history of colorectal cancer is a clinically significant risk factor and may be found in up to 15 percent of all patients with colorectal cancer.2 Hereditary nonpolyposis colorectal cancer, or the Lynch syndrome, is the most common type of familial colorectal cancer and is thought to account for 1 to 5 percent of all cases of the disease.3,4 Members of families with hereditary nonpolyposis colorectal cancer are also at risk for tumors at other sites, including the endometrium, stomach, small intestine, brain, hepatobiliary system, urinary tract, and ovary.2,5 In addition, multiple synchronous or metachronous cancers develop in about 30 percent of the patients.2,5
Hereditary nonpolyposis colorectal cancer is caused by germ-line mutations in one of five DNA mismatch-repair genes: MSH2, 6 MLH1, 7,8 PMS1, PMS2, 9 and MSH6 (also known as GTBP).10,11 Of the 126 germ-line mutations reported to date, almost all have been found in MSH2 and MLH1; only 3 have been reported in PMS1 and PMS2. 12 Recently, two germ-line mutations have been found in MSH6. 10,11 Inactivation of any one of these genes causes widespread genomic instability characterized by the expansion or contraction of short, repeated sequences of DNA (microsatellites).13-15 This phenomenon, known as microsatellite instability, is thought to be responsible for the rapid accumulation of somatic mutations in oncogenes and tumor-suppressor genes that have crucial roles in the initiation and progression of tumors.16-18
In a recent study of the risk of cancer in 19 families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis, we found that the inheritance of a mutated copy of MSH2 or MLH1 is associated with an 80 percent risk of colorectal cancer by the age of 80 years, as compared with a risk of about 4 percent in the general population. Female members of such families also have a 40 to 50 percent risk of endometrial cancer, as compared with a risk of less than 2 percent in the general population. Moreover, carriers of an MSH2 mutation have a higher risk of extracolonic cancers than carriers of an MLH1 mutation.19 A study of mutation carriers identified among patients with an early onset of colorectal cancer confirmed the high risk of endometrial cancer in female family members and found that males had a higher risk of colorectal cancer than females; the risk of colorectal cancer among female carriers was only 30 percent.20
In 1990, the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer proposed a set of clinical diagnostic criteria (later termed the Amsterdam criteria) to provide uniformity in collaborative studies. For families to be classified as having hereditary nonpolyposis colorectal cancer, at least three members in at least two successive generations must have colorectal cancer, with at least one case diagnosed before the age of 50 years; one of the affected members should be a first-degree relative of the other two; and familial adenomatous polyposis should be ruled out.21 Germ-line mutations of MSH2 and MLH1 occur with approximately equal frequency in kindreds who meet the Amsterdam criteria (approximately 25 percent in each case),22-27 whereas such mutations were found in only 10 percent of the kindreds that did not meet the criteria.28,29
The detection of pathogenic mutations in families with hereditary nonpolyposis colorectal cancer has made presymptomatic diagnosis possible in persons who may be at risk. Screening for mutations, however, is time consuming and expensive because of the heterogeneity of the mutations in DNA mismatch-repair genes.12,25,26,29 Moreover, the number of kindreds with an apparent familial clustering of this common cancer is potentially high. Little is known about the clinical risk factors that best predict the presence of MSH2 or MLH1 mutations.28,30 To address this issue, we used denaturing gradient gel electrophoresis (DGGE) with guanosine and cytidine extensions (GC clamping)31,32 to analyze the MSH2 and MLH1 genes in 184 unrelated kindreds with familial clustering of colorectal and other cancers. Using logistic-regression analysis, we devised a method for evaluating the probability of an MSH2 or an MLH1 mutation that is based on several risk factors.
Methods
Subjects
A total of 184 kindreds participated in the study. The results of mutation analysis and assessments of the risk of cancer in some of these families have been reported previously.19,25,26,29 Sixty-seven families were recruited through the Foundation for the Detection of Hereditary Tumors in the Netherlands. These kindreds were referred to the foundation from all parts of the Netherlands because they were suspected of having an inherited form of colorectal cancer. Another 56 Dutch families and 56 Norwegian families were enrolled by clinicians or clinical genetics centers. Also included were three Italian families, one Danish family, and one Czech family. Members of these families attended the clinics because of concern about familial risk factors for colorectal cancer.
Data on family history were collected by genetic fieldworkers or clinical geneticists. Pedigrees were traced backward and laterally as far as possible. In addition, information was collected on the type, site, and number of cancers; the age at diagnosis; and the pathological characteristics of the individual tumors in each of the affected persons. The pedigrees of most families included at least three generations. Eighty-seven percent of the cases of cancer were confirmed by medical or pathology reports or both.
All participating family members gave informed consent, and when their blood samples were collected, they were informed of the possibility of genetic counseling if a pathogenic mutation was identified. The protocol for presymptomatic testing of DNA used by the Dutch clinical genetics centers usually involves three sessions. The issues discussed during the first session include the reasons for DNA testing, the clinical features of hereditary nonpolyposis colorectal cancer, the mode of inheritance of the syndrome, and the DNA-testing procedure. In session 2, the consequences of the test results and the options for treatment in the case of a positive result are discussed, and blood samples are taken. The results of the DNA test are disclosed during session 3. All sessions are conducted by a clinical geneticist with the support of a psychologist or a social worker who is also responsible for the patient's follow-up.
Ninety-two families met the Amsterdam criteria for hereditary nonpolyposis colorectal cancer. Among the 92 kindreds that did not meet the criteria, the majority (48 kindreds) had fewer than the minimal number of three family members with colorectal cancer. In 17 families, colorectal cancer was diagnosed in all affected patients after the age of 50 years, in 11 families only one generation was affected, and in 6 families the affected patients were not first-degree relatives. In the remaining 10 families more than one of the criteria were not met.
Mutation Analysis
Isolation of genomic DNA, amplification with the polymerase chain reaction (PCR), mutation analysis with DGGE, and determination of the nucleotide sequences were performed as previously described.25,26,29,33 In short, the general strategy was to amplify by PCR each of the 16 exons of MSH2 and 19 exons of MLH1 in a single affected member in each family and to analyze these products by GC-clamped DGGE.32 Exons with altered patterns of migration on DGGE were sequenced to determine the molecular nature of the variant. When variants were detected, the investigations were extended, when possible, to the rest of the family to verify the segregation of the nucleotide change with the disease phenotype.25,26,29
Statistical Analysis
We used univariate and multivariate analyses to examine possible associations between specific clinical features and the presence of an MSH2 or MLH1 mutation. For univariate analysis, the Pearson chi-square test was used to identify associations. The following variables were examined within each kindred: the mean age at diagnosis of colorectal cancer, whether or not the Amsterdam criteria were met, the number of family members with colorectal cancer, the number with endometrial cancer, the presence of a patient with other cancers related to hereditary nonpolyposis colorectal cancer, and the presence of a patient with multiple synchronous or metachronous cancers in a family. All these variables were also used in the multivariate analysis. Using logistic regression with backward selection, we calculated the logarithm of the odds of having a deleterious mutation as a linear function of the variables that were significant in the multivariate analysis. To determine the probability of an MSH2 or MLH1 mutation (p), we used the following equation:
log (p/1 + p) = α + β1V1 + β2V2 + . . . + βkVK,
where V1, V2, and . . . VK are the variables being considered and α, β1, β2, and . . . βk are the usual weighted regression values estimated from the data. Eleven of the 184 families were excluded from these analyses, 6 because of the presence of missense mutations of unknown clinical significance and 5 because data relative to the age at diagnosis were not available.
Results
Mutation Analysis
A total of 47 disease-causing mutations were identified in 184 families (26 percent). Of these mutations 19 were in MSH2 and 28 in MLH1. Table 1Table 1
Frequency of MSH2 and MLH1 Mutations According to the Number of Patients with Cancer within a Family., Table 2Table 2
Frequency of MSH2 and MLH1 Mutations According to the Average Age at Diagnosis of Colorectal Cancer of All Patients within a Family., Table 3Table 3
Frequency of MSH2 and MLH1 Mutations in Families with Synchronous and Metachronous Cancers., and Table 4Table 4
Frequency of MSH2 and MLH1 Mutations According to the Types of Extracolonic Cancer within a Family. show the frequency of mutations in MSH2 and MLH1 according to the number of patients with colorectal or endometrial cancer in a kindred, the average age at diagnosis of all colorectal cancers, the number of family members with multiple cancers, and the types of extracolonic cancers, respectively. In addition, six missense mutations of unknown clinical significance were found. Three of these mutations were in MSH2 (Ala→Thr at codon 305, Phe→Val at codon 447, and Ala→Thr at codon 834), and three were in MLH1 (Gln→Lys at codon 62, Asn→Ser at codon 64, and Val→Met at codon 716). Although these mutations were not found in 100 control subjects (including 50 with polyposis), the results of an examination of the cosegregation of the alterations with the disease phenotype were inconclusive. Therefore, we decided to exclude these missense mutations from the statistical analyses.Statistical Analysis
In the univariate analysis, several factors were strongly associated with the presence of mutations in MSH2 or MLH1: younger age at diagnosis of colorectal cancer (P<0.001), fulfillment of the Amsterdam criteria (P<0.001), a higher number of patients with colorectal cancer in a family (P<0.001), the presence of endometrial cancer (P<0.001), a higher number of patients with endometrial cancer in a family (P<0.001), the presence of small-bowel cancer (P<0.05), the presence of multiple colorectal cancers in a single member of a family (P<0.001), and the presence of concomitant colorectal and endometrial cancer in a patient (P<0.001) (Table 5Table 5
Results of Univariate and Multivariate Analyses.). No significant association was found between MSH2 or MLH1 mutations and tumors of the stomach, brain, urinary tract, ovary, or hepatobiliary system or with the presence in a single family member of concomitant colorectal cancer and a tumor related to hereditary nonpolyposis colorectal cancer.In the multivariate analysis, only a younger age at diagnosis of colorectal cancer within a family (P<0.001), fulfillment of the Amsterdam criteria (P<0.001), and the presence of endometrial cancer (P<0.001) were independent risk factors (Table 5). Therefore, we analyzed the probability of detecting a deleterious mutation in MSH2 or MLH1 using logistic regression as a function of the mean age at diagnosis of colorectal cancer in a family, the presence or absence of endometrial cancer, and fulfillment or nonfulfillment of the Amsterdam criteria. The results, expressed as the log odds ratios and their 95 percent confidence intervals, are shown in Figure 1AFigure 1
Estimated Probability of a Deleterious MSH2 or MLH1 Mutation as a Function of the Mean Age at Diagnosis of Colorectal Cancer within a Family and Whether the Amsterdam Criteria Were Met in Families with No Members with Endometrial Cancer (Panel A) and in Families with at Least One Member with Endometrial Cancer (Panel B). and Figure 1B.Given these results, we calculated the predicted probability of detecting MSH2 or MLH1 mutations in individual families (p) with the following equation:
p = eL / (1 + eL),
where e is the exponential function and L is the log odds. Using the equation described in the Methods section, we calculated the log odds ratios with the following formula:
L = 1.4 + [–0.1]V1 + 1.7 V2 + 2.4 V3,
where V1 is the mean age at diagnosis of colorectal cancer of all affected members of a family; V2 equals 1 if at least one member of the family has endometrial cancer and equals 0 otherwise; and V3 equals 1 if the family meets the Amsterdam criteria and equals 0 otherwise (Table 5). For example, the estimated probability of detecting a deleterious mutation in a family that met the Amsterdam criteria and in which the mean age at the diagnosis of colorectal cancer was 40 years is 48 percent (95 percent confidence interval, 31 to 65 percent). If this family also includes a patient with endometrial cancer, then the estimated probability is 83 percent (95 percent confidence interval, 68 to 92 percent). The optimal use of the equation requires a detailed family history and knowledge of all cases of cancer in the family.
To assess which variables are significant predictive factors in the absence of the Amsterdam criteria, we repeated the multivariate analysis after excluding these criteria. In this case, a younger age at the diagnosis of colorectal cancer and a higher number of patients with colorectal or endometrial cancer are independent risk factors. The predicted probability of detecting MSH2 or MLH1 mutations in individual families can be calculated with the other coefficients reported in Table 5.
Discussion
A recent review of 126 different mutations of DNA mismatch-repair genes from 202 kindreds with hereditary nonpolyposis colorectal cancer12 confirmed that MSH2 and MLH1 are responsible for the majority of cases of hereditary nonpolyposis colorectal cancer. The mutations are scattered along the coding regions of both genes, with some clustering in exon 12 of MSH2 and exon 16 of MLH1. The majority of MSH2 mutations are chain-terminating, whereas both nonsense and missense mutations are found in MLH1. The heterogeneity of the MSH2 and MLH1 mutations implies that both genes need to be screened exon by exon for an accurate molecular diagnosis of hereditary nonpolyposis colorectal cancer. Such an approach is laborious and expensive. Screening costs might be reduced if clinical factors that predict the outcome of genetic testing could be identified.
In the present study, we found that an early age of onset of colorectal cancer, fulfillment of the Amsterdam criteria, and the presence in a kindred of a patient with cancer of the endometrium or small bowel, multiple colorectal cancers, or both colorectal and endometrial cancer are strong predictive factors for the presence of MSH2 or MLH1 mutations. For example, if a kindred that met the Amsterdam criteria (mutation-detection rate, 45 percent) also included one patient with endometrial cancer, then the observed rate of detection increases to 71 percent. And, in a family that met the Amsterdam criteria and had one member with both colorectal and endometrial cancer, the likelihood of finding the disease-causing germ-line mutation rises to about 90 percent. Multivariate analysis indicated that only a younger age at diagnosis, fulfillment of the Amsterdam criteria, and the presence of endometrial cancer are independent predictive variables. If the Amsterdam criteria are excluded as a variable in the analysis, a younger age at diagnosis of colorectal cancer and a higher number of patients in the kindred with colorectal or endometrial cancer become independent risk factors.
Our logistic model can be used to estimate the probability of detecting a germ-line mutation on the basis of the clinical features of a kindred with familial clustering of colorectal cancer and other tumors related to hereditary nonpolyposis colorectal cancer. The probability of finding an MSH2 or MLH1 mutation can be deduced from Figure 1A and Figure 1B or calculated with the use of simple software available at the Web site of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer (http://www.nfdht.nl). If the predicted probability is low, one might consider performing microsatellite-instability analysis of the DNA of the colon tumor, which gives an indication of whether there is a mutation of a mismatch-repair gene. Patients with positive results can then undergo mutation analysis. Since the cost of microsatellite-instability analysis is about half that of mutation analysis, this type of analysis will be more cost effective than primary mutation analysis as a first step only if the expected proportion of patients with tumors with microsatellite instability is less than 50 percent. Our preliminary data, which are based on a limited number of tumor samples, indicate that most colorectal tumors from kindreds with hereditary nonpolyposis colorectal cancer that meet the Amsterdam criteria show microsatellite instability, whereas the opposite is true for tumors from families that do not meet the Amsterdam criteria.29 Moreover, recent studies20,34 showed that 57 percent of colorectal cancers that were diagnosed in a patient before the age of 35 years had microsatellite instability and that a germ-line mutation was detected in 25 percent of all cases. These observations suggest that the proportion of patients with tumors with microsatellite instability will drop below 50 percent when the probability of a mutation is less than 20 percent. In these cases, microsatellite-instability analysis of tumor DNA should be considered as a first diagnostic step. Figure 2Figure 2
Strategy of Molecular Analysis in Families Suspected of Having Hereditary Nonpolyposis Colorectal Cancer. illustrates our recommended strategy.Aaltonen et al.4 evaluated the frequency of hereditary nonpolyposis colorectal cancer in Finland by screening colorectal tumors from 509 patients for microsatellite instability and by performing mutation analysis of the tumors with positive results. Tumors from 63 patients showed microsatellite instability, and 10 of these patients had a germ-line mutation of MSH2 or MLH1. Nine of the 10 patients had a first-degree relative with colorectal or endometrial cancer, 7 were under 50 years of age, and 4 had had colorectal or endometrial cancer previously. The authors recommended microsatellite-instability analysis for all patients with colorectal cancer who meet one or more of the following criteria: a family history of colorectal or endometrial cancer, an age at diagnosis of less than 50 years, and a history of multiple colorectal or endometrial cancers. We suggest calculating the probability of finding a mutation with our model when clinical and family data are available and selecting patients for either microsatellite-instability analysis or mutation analysis on the basis of the outcome.
Our series of 184 families included 17 families in which no MSH2 or MLH1 mutations were found. These families met all the Amsterdam criteria except one: a diagnosis of colorectal cancer before the age of 50 years. Earlier studies of similar kindreds with a late onset of colorectal cancer revealed phenotypic differences between these families and those with classic hereditary nonpolyposis colorectal cancer: a predilection for tumors in the left colon, the absence of extracolonic cancers, and a relatively high ratio of adenomas to colorectal cancer.35,36 Tests for microsatellite instability in the colorectal tumors of these patients were negative.36 These findings suggest that such families may represent a separate genetic entity. Recently, Laken et al. reported an unusual mutation in the APC gene that is responsible for familial clustering of late-onset colorectal cancer among Ashkenazi Jews.37 Moreover, the clinical picture characteristic of attenuated familial adenomatous polyposis38 (later onset and fewer polyps than in typical familial adenomatous polyposis) could easily be misinterpreted as that of hereditary nonpolyposis colorectal cancer. Similar atypical APC mutations may also be responsible for a proportion of cases in the 17 families in our study.
The Amsterdam criteria were established to help ensure the uniformity of collaborative studies of hereditary nonpolyposis colorectal cancer.21 The high rate at which mutations were detected among kindreds that meet these criteria and the low percentage of mutations in families that do not confirmed the value of these criteria in selecting patients for screening for mutations of mismatch-repair genes.29 However, the Amsterdam criteria have been criticized as being too stringent and for excluding extracolonic cancers known to be associated with hereditary nonpolyposis colorectal cancer. Moreover, it is obviously harder for small families to fulfill the criteria. Our study shows that endometrial cancer and, to a lesser extent, tumors of the small bowel are important predictive risk factors. These findings suggest that the Amsterdam criteria should be modified to include these extracolonic cancers.
In conclusion, we detected mutations in DNA mismatch-repair genes in a minority (26 percent) of 184 kindreds with familial clustering of colorectal cancers suggestive of hereditary nonpolyposis colorectal cancer. Using logistic-regression analysis, we devised a simple method for calculating the likelihood of detecting MSH2 or MLH1 germ-line mutations. The majority of the kindreds we studied are representative of families that are often referred to clinical geneticists for evaluation of the risk of hereditary colorectal cancer. An accurate estimate of the probability of MSH2 or MLH1 mutations in these families will not only allow a cost-effective strategy for molecular analyses but also help clinicians counsel such families.
Supported in part by the Dutch Cancer Society and Praeventiefonds and by a grant (118571/320) from the Norges Forskningsraad (to Drs. Møller and Heimdal).
This work is dedicated to the memory of Dr. P. Meera Khan.
Source Information
From the Departments of Human Genetics (J.T.W., P.M.K., H.K., A.M., R.F.), Gastroenterology (H.F.A.V.), and Medical Statistics (A.H.Z.) and the Clinical Genetics Center (C.T.), Leiden University Medical Center, Leiden, the Netherlands; the Foundation for the Detection of Hereditary Tumors, Leiden, the Netherlands (H.F.A.V.); and the Unit of Medical Genetics, Norwegian Radium Hospital, Oslo, Norway (P.M.).
Address reprint requests to Dr. Vasen at the Foundation for the Detection of Hereditary Tumors, Rijnsburgerweg 10, Poortgebouw Zuid, 2333 AA Leiden, the Netherlands.
Other authors were Fred Menko, M.D., Ph.D. (University Hospital Vrije Universiteit, Amsterdam, the Netherlands), Babs Taal, M.D., Ph.D. (Netherlands Cancer Institute, Amsterdam, the Netherlands), Fokko Nagengast, M.D., Ph.D., and Han Brunner, M.D., Ph.D. (Nijmegen University Hospital, Nijmegen, the Netherlands), Jan Kleibeuker, M.D., Ph.D., and Rolf Sijmons, M.D. (University Hospital Groningen, Groningen, the Netherlands), Gerrit Griffioen, M.D., Ph.D., Annette Bröcker-Vriends, M.D., Ph.D., Egbert Bakker, Ph.D., and Inge van Leeuwen-Cornelisse, B.S. (Leiden University Medical Center, Leiden, the Netherlands), Anne Meijers-Heijboer, M.D., Dick Lindhout, M.D., Ph.D., and Martijn Breuning, M.D., Ph.D. (Erasmus University, Rotterdam, the Netherlands), Jan Post, M.D. (Clinical Genetics Center Utrecht, Utrecht, the Netherlands), Cees Schaap, M.D. (Clinical Genetics Center Maastricht, Maastricht, the Netherlands), Jaran Apold, M.D., Ph.D. (Haukeland University Hospital, Bergen, Norway), Ketil Heimdal, Ph.D. (Norwegian Radium Hospital, Oslo, Norway), Lucio Bertario, M.D., Ph.D. (Istituto Nazionale Tumori, Milan, Italy), Marie Luise Bisgaard, M.D. (Danish Hereditary Nonpolyposis Colorectal Cancer Registry, Hvidovre Hospital, Hvidovre, Denmark), and Petr Goetz, M.D., Ph.D. (Charles University, Prague, Czech Republic).
- References
References
1
Kinzler KW ,Vogelstein B . Lessons from hereditary colorectal cancer. Cell 1996;87:159-170
CrossRef | Web of Science | Medline2
Lynch HT ,Smyrk TC ,Watson P , et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104:1535-1549
Web of Science | Medline3
Rodriguez-Bigas MA ,Boland CR ,Hamilton SR , et al. A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997;89:1758-1762
CrossRef | Web of Science | Medline4
Aaltonen LA ,Salovaara R ,Kristo P , et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998;338:1481-1487
Full Text | Web of Science | Medline5
Watson P ,Lynch HT . Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993;71:677-685
CrossRef | Web of Science | Medline6
Leach FS ,Nicolaides NC ,Papadopoulos N , et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993;75:1215-1225
CrossRef | Web of Science | Medline7
Papadopoulos N ,Nicolaides NC ,Wei Y-F , et al. Mutation of a mutL homolog in hereditary colon cancer. Science 1994;263:1625-1629
CrossRef | Web of Science | Medline8
Bronner CE ,Baker SM ,Morrison PT , et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994;368:258-261
CrossRef | Web of Science | Medline9
Nicolaides NC ,Papadopoulos N ,Liu B , et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 1994;371:75-80
CrossRef | Web of Science | Medline10
Akiyama Y ,Sato H ,Yamada T , et al. Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectalcancer kindred. Cancer Res 1997;57:3920-3923
Web of Science | Medline11
Miyaki M ,Konishi M ,Tanaka K , et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet 1997;17:271-272
CrossRef | Web of Science | Medline12
Peltomaki P, Vasen HFA, International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer
CrossRef | Web of Science | Medline13
Aaltonen LA ,Peltomaki P ,Leach FS , et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812-816
CrossRef | Web of Science | Medline14
Ionov Y ,Peinado MA ,Malkhosyan S ,Shibata D ,Perucho M . Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993;363:558-561
CrossRef | Web of Science | Medline15
Thibodeau SN ,Bren G ,Schaid D . Microsatellite instability in cancer of the proximal colon. Science 1993;260:816-819
CrossRef | Web of Science | Medline16
Lazar V ,Grandjouan S ,Bognel C , et al. Accumulation of multiple mutations in tumour suppressor genes during colorectal tumorigenesis in HNPCC patients. Hum Mol Genet 1994;3:2257-2260
CrossRef | Web of Science | Medline17
Markowitz S ,Wang J ,Myeroff L , et al. Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 1995;268:1336-1338
CrossRef | Web of Science | Medline18
Parsons R ,Myeroff LL ,Liu B , et al. Microsatellite instability and mutations of the transforming growth factor β type II receptor gene in colorectal cancer. Cancer Res 1995;55:5548-5550
Web of Science | Medline19
Vasen HFA ,Wijnen JT ,Menko FH , et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 1996;110:1020-1027[Erratum, Gastroenterology 1996;111:1402.]
CrossRef | Web of Science | Medline20
Dunlop MG ,Farrington SM ,Carothers AD , et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 1997;6:105-110
CrossRef | Web of Science | Medline21
Vasen HFA ,Mecklin J-P ,Khan PM ,Lynch HT . The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991;34:424-425
CrossRef | Web of Science | Medline22
Liu B ,Parsons R ,Papadopoulos N , et al. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 1996;2:169-174
CrossRef | Web of Science | Medline23
Kolodner RD ,Hall NR ,Lipford J , et al. Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for MLH1 mutations. Cancer Res 1995;55:242-248
Web of Science | Medline24
Han HJ ,Maruyama M ,Baba S ,Park JG ,Nakamura Y . Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC). Hum Mol Genet 1995;4:237-242
CrossRef | Web of Science | Medline25
Wijnen J ,Vasen H ,Khan PM , et al. Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis. Am J Hum Genet 1995;56:1060-1066
Web of Science | Medline26
Wijnen J ,Khan PM ,Vasen H , et al. Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16. Am J Hum Genet 1996;58:300-307
Web of Science | Medline27
Weber TK ,Conlon W ,Petrelli NJ , et al. Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 eastern United States hereditary nonpolyposis colorectal cancer pedigrees. Cancer Res 1997;57:3798-3803
Web of Science | Medline28
Moslein G ,Tester DJ ,Lindor NM , et al. Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer. Hum Mol Genet 1996;5:1245-1252
CrossRef | Web of Science | Medline29
Wijnen J ,Khan PM ,Vasen H , et al. Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations. Am J Hum Genet 1997;61:329-335
CrossRef | Web of Science | Medline30
Pensotti V ,Radice P ,Presciuttini S , et al. Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes. Genes Chromosomes Cancer 1997;19:135-142
CrossRef | Web of Science | Medline31
Myers RM ,Maniatis T ,Lerman LS . Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol 1987;155:501-527
CrossRef | Web of Science | Medline32
Fodde R ,Losekoot M . Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutat 1994;3:83-94
CrossRef | Web of Science | Medline33
Fodde R ,van der Luijt R ,Wijnen J , et al. Eight novel inactivating germ line mutations at the APC gene identified by denaturing gel electrophoresis. Genomics 1992;13:1162-1168
CrossRef | Web of Science | Medline34
Liu B ,Farrington S ,Peterson GM , et al. Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med 1995;1:348-352
CrossRef | Web of Science | Medline35
Vasen HFA ,Taal BG ,Griffioen G , et al. Clinical heterogeneity of familial colorectal cancer and its influence on screening protocols. Gut 1994;35:1262-1266
CrossRef | Web of Science | Medline36
Jass JR ,Pokos V ,Arnold JL , et al. Colorectal neoplasms detected colonoscopically in at-risk members of colorectal cancer families stratified by the demonstration of DNA microsatellite instability. J Mol Med 1996;74:547-551
Web of Science | Medline37
Laken SJ ,Petersen GM ,Gruber SB , et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet 1997;17:79-83
CrossRef | Web of Science | Medline38
Spirio L ,Olschwang S ,Groden J , et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993;75:951-957
CrossRef | Web of Science | Medline
- Citing Articles (134)
Citing Articles
1
Noralane M. Lindor, Gloria M. Petersen, Amanda B. Spurdle, Bryony Thompson, David E. Goldgar, Stephen N. Thibodeau. (2011) Pancreatic Cancer and a Novel MSH2 Germline Alteration. Pancreas 40:7, 1138-1140
CrossRef2
Nir Lubezky, Menahem Ben-Haim, Guy Lahat, Sylvia Marmor, Irit Solar, Eli Brazowski, Richard Nackache, Joseph M. Klausner. (2011) Intraductal papillary mucinous neoplasm of the pancreas: Associated cancers, family history, genetic predisposition?. Surgery
CrossRef3
Michal Kovac, Endre Laczko, Ritva Haider, Josef Jiricny, Hansjakob Mueller, Karl Heinimann, Giancarlo Marra. (2011) Familial colorectal cancer: eleven years of data from a registry program in Switzerland. Familial Cancer 10:3, 605-616
CrossRef4
Paul J. Limburg, William S. Harmsen, Helen H. Chen, Steven Gallinger, Robert W. Haile, John A. Baron, Graham Casey, Michael O. Woods, Stephen N. Thibodeau, Noralane M. Lindor. (2011) Prevalence of Alterations in DNA Mismatch Repair Genes in Patients With Young-Onset Colorectal Cancer. Clinical Gastroenterology and Hepatology 9:6, 497-502
CrossRef5
Wenqian Wei, Fangqi Liu, Lei Liu, Zuofeng Li, Xiaoyan Zhang, Fan Jiang, Qu Shi, Xiaoyan Zhou, Weiqi Sheng, Sanjun Cai, Xuan Li, Ye Xu, Peng Nan. (2011) Distinct mutations in MLH1 and MSH2 genes in Hereditary Non-polyposis Colorectal Cancer (HNPCC) families from China. BMB Reports 44:5, 317-322
CrossRef6
Maija R.J. Kohonen-Corish, Finlay Macrae, Maurizio Genuardi, Stefan Aretz, Bharati Bapat, Inge T. Bernstein, John Burn, Richard G.H. Cotton, Johan T. den Dunnen, Thierry Frebourg, Marc S. Greenblatt, Robert Hofstra, Elke Holinski-Feder, Ilkka Lappalainen, Annika Lindblom, Donna Maglott, Pål Møller, Hans Morreau, Gabriela Möslein, Rolf Sijmons, Amanda B. Spurdle, Sean Tavtigian, Carli M.J. Tops, Thomas K. Weber, Niels de Wind, Michael O. Woods, . (2011) Deciphering the colon cancer genes-report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010. Human Mutation 32:4, 491-494
CrossRef7
Scott M. Weissman, Cecelia Bellcross, Christina Chimera Bittner, Mary E. Freivogel, Joy Larsen Haidle, Pardeep Kaurah, Anna Leininger, Selvi Palaniappan, Kelle Steenblock, Thuy M. Vu, Molly S. Daniels. (2011) Genetic Counseling Considerations in the Evaluation of Families for Lynch Syndrome—A Review. Journal of Genetic Counseling 20:1, 5-19
CrossRef8
Jeffrey N. Weitzel, Kathleen R. Blazer, Deborah J. MacDonald, Julie O. Culver, Kenneth Offit. (2011) Genetics, genomics, and cancer risk assessment. CA: A Cancer Journal for Cliniciansn/a-n/a
CrossRef9
A. Middeldorp, R. van Eijk, J. Oosting, G.I. Forte, M. van Puijenbroek, M. van Nieuwenhuizen, W.E. Corver, D. Ruano, T. Caldes, J. Wijnen, H. Morreau, T. van Wezel. (2011) Increased frequency of 20q gain and copy-neutral loss of heterozygosity in mismatch repair proficient familial colorectal carcinomas. International Journal of Cancern/a-n/a
CrossRef10
Margot G.F. van Lier, Celine H.M. Leenen, Anja Wagner, Dewkoemar Ramsoekh, Hendrikus J. Dubbink, Ans M.W. van den Ouweland, Pieter J Westenend, Eelco J.R. de Graaf, Leonieke M.M. Wolters, Wietske W. Vrijland, Ernst J Kuipers, Monique E. van Leerdam, Ewout W. Steyerberg, Winand N.M. Dinjens, . (2011) Yield of routine molecular analyses in colorectal cancer patients ≤ 70 years to detect underlying Lynch syndrome. The Journal of Pathologyn/a-n/a
CrossRef11
Neel B. Shah, Noralane M. Lindor. (2010) Lower Gastrointestinal Tract Cancer Predisposition Syndromes. Hematology/Oncology Clinics of North America 24:6, 1229-1252
CrossRef12
Mauro Santibanez Koref, Valerie Wilson, Nicola Cartwright, Michael S. Cunnington, John C. Mathers, D. Timothy Bishop, Ann Curtis, Malcolm G. Dunlop, John Burn. (2010) MLH1 Differential Allelic Expression in Mutation Carriers and Controls. Annals of Human Genetics 74:6, 479-488
CrossRef13
Derek G. Power, Emily Gloglowski, Steven M. Lipkin. (2010) Clinical Genetics of Hereditary Colorectal Cancer. Hematology/Oncology Clinics of North America 24:5, 837-859
CrossRef14
M. H. Abdel-Rahman, R. Pilarski, S. Ezzat, J. Sexton, F. H. Davidorf. (2010) Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma. Familial Cancer 9:3, 431-438
CrossRef15
Simon A Gayther, Paul DP Pharoah. (2010) The inherited genetics of ovarian and endometrial cancer. Current Opinion in Genetics & Development 20:3, 231-238
CrossRef16
Isela Quispe, Judith Balmaña. (2010) Desarrollo y aplicación de modelos predictivos en el síndrome de Lynch. Medicina Clínica 134:9, 412-417
CrossRef17
Christoph Engel, Nils Rahner, Karsten Schulmann, Elke Holinski–Feder, Timm O. Goecke, Hans K. Schackert, Matthias Kloor, Verena Steinke, Holger Vogelsang, Gabriela Möslein, Heike Görgens, Stefan Dechant, Magnus von Knebel Doeberitz, Josef Rüschoff, Nicolaus Friedrichs, Reinhard Büttner, Markus Loeffler, Peter Propping, Wolff Schmiegel. (2010) Efficacy of Annual Colonoscopic Surveillance in Individuals With Hereditary Nonpolyposis Colorectal Cancer. Clinical Gastroenterology and Hepatology 8:2, 174-182
CrossRef18
Anneke Middeldorp, Shantie C. Jagmohan-Changur, Heleen M. van der Klift, Marjo van Puijenbroek, Jeanine J. Houwing-Duistermaat, Emily Webb, Richard Houlston, Carli Tops, Hans F. A. Vasen, Peter Devilee, Hans Morreau, Tom van Wezel, Juul Wijnen. (2010) Comprehensive genetic analysis of seven large families with mismatch repair proficient colorectal cancer. Genes, Chromosomes and CancerNA-NA
CrossRef19
Margot G.F. Van Lier, Anja Wagner, Monique E. Van Leerdam, Katharina Biermann, Ernst J. Kuipers, Ewout W. Steyerberg, Hendrikus Jan Dubbink, Winand N.M. Dinjens. (2010) A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory. Journal of Cellular and Molecular Medicine 14:1-2, 181-197
CrossRef20
Daniel B. Eisen, Daniel J. Michael. (2009) Sebaceous lesions and their associated syndromes: Part II. Journal of the American Academy of Dermatology 61:4, 563-578
CrossRef21
Noralane M. Lindor. (2009) Familial Colorectal Cancer Type X: The Other Half of Hereditary Nonpolyposis Colon Cancer Syndrome. Surgical Oncology Clinics of North America 18:4, 637-645
CrossRef22
Floor J. Backes, Marino E. Leon, Iouri Ivanov, Adrian Suarez, Wendy L. Frankel, Heather Hampel, Jeffrey M. Fowler, Larry J. Copeland, David M. O'Malley, David E. Cohn. (2009) Prospective evaluation of DNA mismatch repair protein expression in primary endometrial cancer. Gynecologic Oncology 114:3, 486-490
CrossRef23
Hui-Ling Yap, Wei-Shieng Chieng, Jasmine Rui-Chen Lim, Robert Seng-Cheong Lim, Ross Soo, Jiayi Guo, Soo-Chin Lee. (2009) Recurring MLH1 deleterious mutations in unrelated Chinese Lynch syndrome families in Singapore. Familial Cancer 8:2, 85-94
CrossRef24
Fay Kastrinos, John I Allen, David H Stockwell, Elena M Stoffel, Earl F Cook, Muthoka L Mutinga, Judith Balmaña, Sapna Syngal. (2009) Development and Validation of a Colon Cancer Risk Assessment Tool for Patients Undergoing Colonoscopy. The American Journal of Gastroenterology 104:6, 1508-1518
CrossRef25
Eli Marie Grindedal, Ignacio Blanco, Astrid Stormorken, Lovise Maehle, Neal Clark, Sara González, Gabriel Capella, Hans Vasen, John Burn, Pål Møller. (2009) High risk of endometrial cancer in colorectal cancer kindred is pathognomonic for MMR-mutation carriers. Familial Cancer 8:2, 145-151
CrossRef26
Carli M.J. Tops, Juul Th. Wijnen, Frederik J. Hes. (2009) Introduction to molecular and clinical genetics of colorectal cancer syndromes. Best Practice & Research Clinical Gastroenterology 23:2, 127-146
CrossRef27
R. C. Green, P. S. Parfrey, M. O. Woods, H. B. Younghusband. (2009) Prediction of Lynch Syndrome in Consecutive Patients With Colorectal Cancer. JNCI Journal of the National Cancer Institute 101:5, 331-340
CrossRef28
Noralane M. Lindor. (2009) Hereditary colorectal cancer: MYH-associated polyposis and other newly identified disorders. Best Practice & Research Clinical Gastroenterology 23:1, 75-87
CrossRef29
Ranjit Manchanda, Usha Menon, Rachel Michaelson-Cohen, Uziel Beller, Ian Jacobs. (2009) Hereditary non-polyposis colorectal cancer or Lynch syndrome: the gynaecological perspective. Current Opinion in Obstetrics and Gynecology 21:1, 31-38
CrossRef30
C-W Wang, EC Hui. (2009) Ethical, legal and social implications of prenatal and preimplantation genetic testing for cancer susceptibility. Reproductive BioMedicine Online 19, 23-33
CrossRef31
Jose G. Monzon, Carol Cremin, Linlea Armstrong, Jennifer Nuk, Sean Young, Doug E. Horsman, Kristy Garbutt, Chris D. Bajdik, Sharlene Gill. (2009) Validation of predictive models for germline mutations in DNA mismatch repair genes in colorectal cancer. International Journal of CancerNA-NA
CrossRef32
Isabelle Tournier, Myriam Vezain, Alexandra Martins, Françoise Charbonnier, Stéphanie Baert-Desurmont, Sylviane Olschwang, Qing Wang, Marie Pierre Buisine, Johann Soret, Jamal Tazi, Thierry Frébourg, Mario Tosi. (2008) A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects. Human Mutation 29:12, 1412-1424
CrossRef33
Harry R. Aslanian, Lawrence J. Burgart, Jonathan J. Harrington, Douglas W. Mahoney, Alan R. Zinsmeister, Stephen N. Thibodeau, David A. Ahlquist. (2008) Altered DNA Mismatch Repair Expression in Synchronous and Metachronous Colorectal Cancers. Clinical Gastroenterology and Hepatology 6:12, 1385-1388
CrossRef34
Elizabeth C. Chao, Jonathan L. Velasquez, Mavee S.L. Witherspoon, Laura S. Rozek, David Peel, Pauline Ng, Stephen B. Gruber, Patrice Watson, Gad Rennert, Hoda Anton-Culver, Henry Lynch, Steven M. Lipkin. (2008) Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR). Human Mutation 29:6, 852-860
CrossRef35
M Dolores Giráldez, Sergi Castellví-Bel, Francesc Balaguer, Victòria Gonzalo, Teresa Ocaña, Antoni Castells. (2008) Lynch syndrome in colorectal cancer patients. Expert Review of Anticancer Therapy 8:4, 573-583
CrossRef36
Shu OKAMURA, Rei SUZUKI, Shin NAKAHIRA, Hirofumi MIKI, Keishi SUGIMOTO, Shigeyuki TAMURA. (2008) A CASE OF MULTIPLE ADENOMAS AND MULTIPLE CANCER OF THE COLON SUGGESTIVE OF HEREDITARY COLORECTAL CANCER. Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 69:6, 1447-1451
CrossRef37
Francesc Balaguer, Judith Balmaña, Sergi Castellví–Bel, Ewout W. Steyerberg, Montserrat Andreu, Xavier Llor, Rodrigo Jover, Sapna Syngal, Antoni Castells. (2008) Validation and Extension of the PREMM1,2 Model in a Population-Based Cohort of Colorectal Cancer Patients. Gastroenterology 134:1, 39-46
CrossRef38
Ewout W. Steyerberg, Judith Balmaña, David H. Stockwell, Sapna Syngal. (2007) Data reduction for prediction: A case study on robust coding of age and family history for the risk of having a genetic mutation. Statistics in Medicine 26:30, 5545-5556
CrossRef39
D. RAMSOEKH, M. E. VAN LEERDAM, A. WAGNER, E. J. KUIPERS. (2007) Review article: detection and management of hereditary non-polyposis colorectal cancer (Lynch syndrome). Alimentary Pharmacology & Therapeutics 26, 101-111
CrossRef40
H. F. A. VASEN. (2007) Review article: the Lynch syndrome (hereditary nonpolyposis colorectal cancer)*. Alimentary Pharmacology & Therapeutics 26, 113-126
CrossRef41
Päivi Peltomäki. (2007) Tracking mutations in a family: Recognizing indicators of germline mutation in Lynch syndrome. Current Colorectal Cancer Reports 3:4, 199-205
CrossRef42
Sining Chen, David M. Euhus, Giovanni Parmigiani. (2007) Quantitative models for predicting mutations in Lynch syndrome genes. Current Colorectal Cancer Reports 3:4, 206-211
CrossRef43
Beth Y. Karlan, Andrew Berchuck, David Mutch. (2007) The Role of Genetic Testing for Cancer Susceptibility in Gynecologic Practice. Obstetrics & Gynecology 110:1, 155-167
CrossRef44
D. W. Anderson, P. A. Goldberg, U. Algar, R. Felix, R. S. Ramesar. (2007) Mobile colonoscopic surveillance provides quality care for hereditary nonpolyposis colorectal carcinoma families in South Africa. Colorectal Disease 9:6, 509-514
CrossRef45
Brenda Diergaarde, Hanneke Braam, Hans F. Vasen, Fokko M. Nagengast, Goos N.P. van Muijen, Frans J. Kok, Ellen Kampman. (2007) Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer. Clinical Gastroenterology and Hepatology 5:6, 736-742.e1
CrossRef46
M. R. Spitz, W. K. Hong, C. I. Amos, X. Wu, M. B. Schabath, Q. Dong, S. Shete, C. J. Etzel. (2007) A Risk Model for Prediction of Lung Cancer. JNCI Journal of the National Cancer Institute 99:9, 715-726
CrossRef47
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Rosenberg, Eric S., Cort, Alice M., Ebeling, Sally H.Peters, Christine C., Seiden, Michael V., Patel, Devanshi, O'Neill, Mary Jane, Oliva, Esther, . (2007) Case 13-2007. New England Journal of Medicine 356:17, 1760-1769
Full Text48
Y. Nancy You, Vipul T. Lakhani, Samuel A. Wells. (2007) The Role of Prophylactic Surgery in Cancer Prevention. World Journal of Surgery 31:3, 450-464
CrossRef49
F Bianchi, E Galizia, R Bracci, L Belvederesi, R Catalani, C Loretelli, G Giorgetti, C Ferretti, I Bearzi, E Porfiri, R Cellerino. (2007) Effectiveness of the crcapro program in identifying patients suspected for HNPCC. Clinical Genetics 71:2, 158-164
CrossRef50
Adrian Cassidy, Stephen W. Duffy, Jonathan P. Myles, Triantafillos Liloglou, John K. Field. (2007) Lung cancer risk prediction: A tool for early detection. International Journal of Cancer 120:1, 1-6
CrossRef51
A. E. Jong, F. M. Nagengast, J. H. Kleibeuker, P. C. Meeberg, H. J. Wijk, A. Cats, G. Griffioen, H. F. A. Vasen. (2006) What is the appropriate screening protocol in Lynch syndrome?. Familial Cancer 5:4, 373-378
CrossRef52
B.M. BUTTIN, M.A. POWELL, P.J. GOODFELLOW, S.N. LEWIN, R.K. GIBB, D.G. MUTCH. (2006) Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability?positive endometrial carcinoma. International Journal of Gynecological Cancer 16:6, 1980-1986
CrossRef53
Kory W. Jasperson, Katrina Lowstuter, Jeffrey N. Weitzel. (2006) Assessing the Predictive Accuracy of hMLH1 and hMSH2 Mutation Probability Models. Journal of Genetic Counseling 15:5, 339-347
CrossRef54
CL Gaff, MT Rogers, IM Frayling. (2006) Variability and inequity in testing of somatic tissue for hereditary cancer: a survey of UK clinical practice. Clinical Genetics 70:4, 312-319
CrossRef55
Carolyn Farrell, Mollie Lyman, Katherine Freitag, Cathy Fahey, M Steven Piver, Kerry J. Rodabaugh. (2006) The role of hereditary nonpolyposis colorectal cancer in the management of familial ovarian cancer. Genetics in Medicine 8:10, 653-657
CrossRef56
Carol A. Durno, Steven Gallinger. (2006) Genetic Predisposition to Colorectal Cancer. Journal of Pediatric Gastroenterology and Nutrition 43:1, 5-15
CrossRef57
Barnetson, Rebecca A., Tenesa, Albert, Farrington, Susan M., Nicholl, Iain D., Cetnarskyj, Roseanne, Porteous, Mary E., Campbell, Harry, Dunlop, Malcolm G., . (2006) Identification and Survival of Carriers of Mutations in DNA Mismatch-Repair Genes in Colon Cancer. New England Journal of Medicine 354:26, 2751-2763
Full Text58
M. Spaepen, B. Vankeirsbilck, S. Opstal, S. Tejpar, E. Cutsem, K. Geboes, E. Legius, G. Matthijs. (2006) Germline Mutations of the hMLH1 and hMSH2 Mismatch Repair Genes in Belgian Hereditary Nonpolyposis Colon Cancer (HNPCC) Patients. Familial Cancer 5:2, 179-189
CrossRef59
Francisco Rodriguez-Moranta, Antoni Castells, Montserrat Andreu, Virginia Pinol, Sergi Castellvi-Bel, Cristina Alenda, Xavier Llor, Rosa M. Xicola, Rodrigo Jover, Artemio Paya, Xavier Bessa, Francesc Balaguer, Joaquin Cubiella, Lidia Arguello, Juan Diego Morillas, Luis Bujanda, . (2006) Clinical Performance of Original and Revised Bethesda Guidelines for the Identification of MSH2/MLH1 Gene Carriers in Patients with Newly Diagnosed Colorectal Cancer: Proposal of a New and Simpler Set of Recommendations. The American Journal of Gastroenterology 101:5, 1104-1111
CrossRef60
Laura Cerezo, Higinia Cárdenes, Helen Michael. (2006) Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. Clinical & Translational Oncology 8:4, 231-241
CrossRef61
A Kataki, IP Gomatos, K Arapis, S Mparatsis, P Alepas, A Kaintatzis, M Nikolopoulou, E Leandros, MM Konstadoulakis, J Bramis. (2006) HMLH1 and HMSH2 germline mutations in Greek families with hereditary non-polyposis colorectal cancer. Clinical Genetics 69:3, 290-293
CrossRef62
F Marroni, C Pastrello, P Benatti, M Torrini, D Barana, EL Cordisco, A Viel, C Mareni, C Oliani, M Genuardi, JE Bailey-Wilson, M Ponz de Leon, S Presciuttini. (2006) A genetic model for determining MSH2 and MLH1 carrier probabilities based on family history and tumor microsatellite instability. Clinical Genetics 69:3, 254-262
CrossRef63
Yvonne M.C. Hendriks, Shantie Jagmohan–Changur, Heleen M. van der Klift, Hans Morreau, Marjo van Puijenbroek, Carli Tops, Theo van Os, Anja Wagner, Margreet G.F.M. Ausems, Encarna Gomez, Martijn H. Breuning, Annette H.J.T. Bröcker–Vriends, Hans F.A. Vasen, Juul Th. Wijnen. (2006) Heterozygous Mutations in PMS2 Cause Hereditary Nonpolyposis Colorectal Carcinoma (Lynch Syndrome). Gastroenterology 130:2, 312-322
CrossRef64
Ian Frayling. 2006. Hereditary Nonpolyposis Colorectal Cancer. .
CrossRef65
Astrid T. Stormorken, Geir Hoff, Jarle Norstein, Inger Marie Bowitz-Lothe, Eldbjørg Hanslien, Eli Grindedal, Pål Møller. (2006) Estimated prevalence of hereditary cancers and the need for surveillance in a Norwegian county, Telemark. Scandinavian Journal of Gastroenterology 41:1, 71-79
CrossRef66
Alejandro Giraldo, Andrea Gómez, Gustavo Salguero, Herbert García, Fabio Aristizábal, Óscar Gutiérrez, Luis Alberto Ángel, Jorge Padrón, Carlos Martínez, Humberto Martínez, Omar Malaver, Luis Flórez, Rosa Barvo. (2005) MLH1 and MSH2 Mutations in Colombian Families with Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome) – Description of Four Novel Mutations. Familial Cancer 4:4, 285-290
CrossRef67
Pierre-Olivier Schischmanoff, Christine Lagorce, Philippe Wind, Robert Benamouzig. (2005) Le syndrome HNPCC (Hereditary Non Polyposis Colon Cancer). Gastroentérologie Clinique et Biologique 29:10, 1028-1034
CrossRef68
Heleen van der Klift, Juul Wijnen, Anja Wagner, Paul Verkuilen, Carli Tops, Robyn Otway, Maija Kohonen-Corish, Hans Vasen, Cristina Oliani, Daniela Barana, Pal Moller, Celia DeLozier-Blanchet, Pierre Hutter, William Foulkes, Henry Lynch, John Burn, Gabriela Möslein, Riccardo Fodde. (2005) Molecular characterization of the spectrum of genomic deletions in the mismatch repair genesMSH2,MLH1,MSH6, andPMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Genes, Chromosomes and Cancer 44:2, 123-138
CrossRef69
Ismail Jatoi, William F. Anderson. (2005) Cancer Screening. Current Problems in Surgery 42:9, 620-682
CrossRef70
S-C Lee, J-Y Guo, R Lim, R Soo, E Koay, M Salto-Tellez, A Leong, B-C Goh. (2005) Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia. Clinical Genetics 68:2, 137-145
CrossRef71
Yuki Young, Jonathan P. Terdiman. (2005) Endoscopic Management of Familial Colonic Neoplasia. Gastrointestinal Endoscopy Clinics of North America 15:3, 549-580
CrossRef72
Yves Bécouarn, Anne Rullier, Philippe Gorry, Denis Smith, Bruno Richard-Molard, Emmanuel Echinard, Patrick Texereau, Richard Beyssac, Jean-Louis Legoux, Hervé Lamouliatte, Thierry Frebourg, Sylviane Olschwang, Brigitte Gilbert, Laurence Venat, Véronique Picot, François Paraf, Michel Longy. (2005) Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. Gastroentérologie Clinique et Biologique 29:6-7, 667-675
CrossRef73
A. N. Freedman, D. Seminara, M. H. Gail, P. Hartge, G. A. Colditz, R. Ballard-Barbash, R. M. Pfeiffer. (2005) Cancer Risk Prediction Models: A Workshop on Development, Evaluation, and Application. JNCI Journal of the National Cancer Institute 97:10, 715-723
CrossRef74
Randall Burt, Deborah W. Neklason. (2005) Genetic Testing for Inherited Colon Cancer. Gastroenterology 128:6, 1696-1716
CrossRef75
Jonathan P. Terdiman. (2005) Colorectal cancer at a young age. Gastroenterology 128:4, 1067-1076
CrossRef76
Paul C. Schroy, Julie T. Glick, Alan C. Geller, Angela Jackson, Timothy Heeren, Marianne Prout. (2005) A Novel Educational Strategy to Enhance Internal Medicine Residents' Familial Colorectal Cancer Knowledge and Risk Assessment Skills. The American Journal of Gastroenterology 100:3, 677-684
CrossRef77
Won-Seok Jo, Daniel C. Chung. (2005) Genetics of hereditary colorectal cancer. Seminars in Oncology 32:1, 11-23
CrossRef78
A. Arrigoni, T. Sprujevnik, V. Alvisi, A. Rossi, G. Ricci, M. Pennazio, M. Spandre, M. Cavallero, A. Bertone, A. Foco, F.P. Rossini. (2005) Clinical identification and long-term surveillance of 22 hereditary non-polyposis colon cancer Italian families. European Journal of Gastroenterology & Hepatology 17:2, 213-219
CrossRef79
PJ Ainsworth, D. Koscinski, BP Fraser, JA Stuart. (2004) Family cancer histories predictive of a high risk of hereditary non-polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1. Clinical Genetics 66:3, 183-188
CrossRef80
Pedro A. Lage, Cristina Albuquerque, Rita G. Sousa, Marilia L. Cravo, Maria Salazar, In
s Francisco, Lara Maia, Isabel Claro, Alexandra Suspiro, Paula Rodrigues, H
CrossRef81
W Kievit, JHFM De Bruin, EMM Adang, MJL Ligtenberg, FM Nagengast, JHJM Van Krieken, N Hoogerbrugge. (2004) Current clinical selection strategies for identification of hereditary non-polyposis colorectal cancer families are inadequate: a meta-analysis. Clinical Genetics 65:4, 308-316
CrossRef82
Steven Gallinger, Melyssa Aronson, Katayoon Shayan, Elyanne M. Ratcliffe, Justin T. Gerstle, Patricia C. Parkin, Heidi Rothenmund, Marina Croitoru, Ewa Baumann, Peter R. Durie, Rosanna Weksberg, Aaron Pollett, Robert H. Riddell, Bo Y. Ngan, Ernest Cutz, Alain E. Lagarde, Helen S.L. Chan. (2004) Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation. Gastroenterology 126:2, 576-585
CrossRef83
G. guillem Jose, G. moore Harvey, Palmer Crystal, Glogowski Emily, Rob Finch, Nafa Khedoudja, J. Markowitz Arnold, Offit Kenneth, A. Ellis Nathan. (2004) A636P testing in Ashkenazi Jews. Familial Cancer 3:3-4, 223-227
CrossRef84
Hwei-Ju Annie Yu, Kevin M Lin, David M Ota, Henry T Lynch. (2003) Hereditary nonpolyposis colorectal cancer: preventive management. Cancer Treatment Reviews 29:6, 461-470
CrossRef85
Anja Wagner, Alicia Barrows, Juul Th. Wijnen, Heleen van der Klift, Patrick F. Franken, Paul Verkuijlen, Hidewaki Nakagawa, Marjan Geugien, Shantie Jaghmohan-Changur, Cor Breukel, Hanne Meijers-Heijboer, Hans Morreau, Marjo van Puijenbroek, John Burn, Stephany Coronel, Yulia Kinarski, Ross Okimoto, Patrice Watson, Jane F. Lynch, Albert de la Chapelle, Henry T. Lynch, Riccardo Fodde. (2003) Molecular Analysis of Hereditary Nonpolyposis Colorectal Cancer in the United States: High Mutation Detection Rate among Clinically Selected Families and Characterization of an American Founder Genomic Deletion of the MSH2 Gene. The American Journal of Human Genetics 72:5, 1088-1100
CrossRef86
William M. Grady. (2003) Genetic testing for high-risk colon cancer patients1 1Abbreviations used in this paper: FAP, familial adenomatous polyposis; HMPS, hereditary mixed polyposis syndrome; HNPCC, hereditary nonpolyposis colon cancer; JPS, juvenile polyposis; MMR, mutation mismatch repair; MSI, microsatellite instability; PJS, Peutz-Jeghers syndrome; TGF, transforming growth factor.. Gastroenterology 124:6, 1574-1594
CrossRef87
José G Guillem, Beth S Rapaport, Tomas Kirchhoff, Prema Kolachana, Khedoudja Nafa, Emily Glogowski, Rob Finch, Helen Huang, William D Foulkes, Arnold Markowitz, Nathan A Ellis, Kenneth Offit. (2003) A636P is associated with early-onset colon cancer in Ashkenazi Jews. Journal of the American College of Surgeons 196:2, 222-225
CrossRef88
M. Keller, R. Jost, C. Mastromarino Haunstetter, P. Kienle, H.-P. Knaebel, J. Gebert, C. Sutter, M. V. Knebel-Doeberitz, F. Cremer, U. Mazitschek. (2002) Comprehensive Genetic Counseling for Families At Risk for HNPCC: Impact on Distress and Perceptions. Genetic Testing 6:4, 291-302
CrossRef89
Mark A. Jenkins, Laura Baglietto, Gillian S. Dite, Damien J. Jolley, Melissa C. Southey, Jonathan Whitty, Leeanne J. Mead, D. James B. St. John, Finlay A. Macrae, D. Timothy Bishop, Deon J. Venter, Graham G. Giles, John L. Hopper. (2002) AfterhMSH2 andhMLH1?what next? Analysis of three-generational, population-based, early-onset colorectal cancer families. International Journal of Cancer 102:2, 166-171
CrossRef90
Carolina M. Reyes, Brian A. Allen, Jonathan P. Terdiman, Leslie S. Wilson. (2002) Comparison of selection strategies for genetic testing of patients with hereditary nonpolyposis colorectal carcinoma. Cancer 95:9, 1848-1856
CrossRef91
J. D. Trimbath, F. M. Giardiello. (2002) Genetic testing and counselling for hereditary colorectal cancer. Alimentary Pharmacology and Therapeutics 16:11, 1843-1857
CrossRef92
J J P Gille, F B L Hogervorst, G Pals, JTh Wijnen, R J van Schooten, C J Dommering, G A Meijer, M E Craanen, P M Nederlof, D de Jong, C J McElgunn, J P Schouten, F H Menko. (2002) Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach. British Journal of Cancer 87:8, 892-897
CrossRef93
William M. Grady, Sanford D. Markowitz. (2002) G
ENETIC AND EPIGENETIC ALTERATIONS IN COLON CANCER . Annual Review of Genomics and Human Genetics 3:1, 101-128
CrossRef94
Anja Wagner, Heleen van der Klift, Patrick Franken, Juul Wijnen, Cor Breukel, Vladimir Bezrookove, Ron Smits, Yulia Kinarsky, Alicia Barrows, Barbara Franklin, Jane Lynch, Henry Lynch, Riccardo Fodde. (2002) A 10-Mb paracentric inversion of chromosome arm 2p inactivatesMSH2 and is responsible for hereditary nonpolyposis colorectal cancer in a North-American kindred. Genes, Chromosomes and Cancer 35:1, 49-57
CrossRef95
Marie Luise Bisgaard, Anne Charlotte J
CrossRef96
Maria Planck, Eva Rambech, Gabriela M
CrossRef97
Alexandra M. Easson, Michelle Cotterchio, Jacqueline A. Crosby, Heather Sutherland, Darlene Dale, Melyssa Aronson, Eric Holowaty, Steven Gallinger. (2002) A population-based study of the extent of surgical resection of potentially curable colon cancer. Annals of Surgical Oncology 9:4, 380-387
CrossRef98
Trinidad Caldes, Javier Godino, Miguel de la Hoya, Iciar Garcia Carbonero, Pedro Perez Segura, Charis Eng, Manuel Benito, Eduardo Diaz-Rubio. (2002) Prevalence of germline mutations ofMLH1 andMSH2 in hereditary nonpolyposis colorectal cancer families from Spain. International Journal of Cancer 98:5, 774-779
CrossRef99
Jonathan P. Terdiman, Theodore R. Levin, Brian A. Allen, James R. Gum, Andrea Fishbach, Peggy G. Conrad, Glenn A. Miller, Vivian Weinberg, Ronald Bachman, Joann Bergoffen, Ann Stembridge, Neil W. Toribara, Marvin H. Sleisenger, Young S. Kim. (2002) Hereditary nonpolyposis colorectal cancer in young colorectal cancer patients: High-risk clinic versus population-based registry. Gastroenterology 122:4, 940-947
CrossRef100
Maran J.W. Berends, Ying Wu, Rolf H. Sijmons, Rob G.J. Mensink, Tineke van der Sluis, Jannet M. Hordijk-Hos, Elisabeth G.E. de Vries, Harry Hollema, Arend Karrenbeld, Charles H. C.M. Buys, Ate G.J. van der Zee, Robert M.W. Hofstra, Jan H. Kleibeuker. (2002) Molecular and Clinical Characteristics of MSH6 Variants: An Analysis of 25 Index Carriers of a Germline Variant. The American Journal of Human Genetics 70:1, 26-37
CrossRef101
Sandrine Jacob, Françoise Praz. (2002) DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 84:1, 27-47
CrossRef102
June Peters, Jennifer Loud, Eileen Dimond, Jeanne Jenkins. (2001) Cancer Genetics Fundamentals. Cancer Nursing 24:6, 446-461
CrossRef103
Jennifer G. Cohen, Thaddeus P. Dryja, Katherine B. Davis, Lisa R. Diller, Frederick P. Li. (2001) RB1 genetic testing as a clinical service: A follow-up study. Medical and Pediatric Oncology 37:4, 372-378
CrossRef104
Hans-Peter Wüllenweber, Christian Sutter, Frank Autschbach, Frank Willeke, Peter Kienle, Axel Benner, Joachim Bähring, Martina Kadmon, Christian Herfarth, Magnus von Knebel Doeberitz, Johannes Gebert. (2001) Evaluation of bethesda guidelines in relation to microsatellite instability. Diseases of the Colon & Rectum 44:9, 1281-1289
CrossRef105
Jon Emery, Anneke Lucassen, Michael Murphy. (2001) Common hereditary cancers and implications for primary care. The Lancet 358:9275, 56-63
CrossRef106
Noralane M. Lindor, Christopher B. Dechet, Mark H. Greene, Robert B. Jenkins, M. Tanja Zincke, Amy L. Weaver, Marcia Wilson, Horst Zincke, Wanguo Liu. (2001) Papillary Renal Cell Carcinoma: Analysis of Germline Mutations in the MET Proto-Oncogene in a Clinic-Based Population. Genetic Testing 5:2, 101-106
CrossRef107
Herbert J. Van Kruiningen, Antoine Cortot, Jean-Fr??d??ric Colombel. (2001) The Importance of Familial Clusterings in Crohn???s Disease. Inflammatory Bowel Diseases 7:2, 170-173
CrossRef108
B. Bittorf, H. Kessler, S. Merkel, W. Brückl, A. Wein, W.G. Ballhausen, W. Hohenberger, K. Günther. (2001) Multiple primary malignancies: An epidemiological and pedigree analysis of 57 patients with at least three tumours. European Journal of Surgical Oncology (EJSO) 27:3, 302-313
CrossRef109
Rogério Rabelo, William Foulkes, Philip H. Gordon, Nora Wong, Zhi Qiang Yuan, Elizabeth MacNamara, George Chong, Leonard Pinsky, Dana Lasko. (2001) Role of molecular diagnostic testing in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families. Diseases of the Colon & Rectum 44:3, 437-446
CrossRef110
Rodney J. Scott, Mary McPhillips, Cliff J. Meldrum, Patrick E. Fitzgerald, Kirsten Adams, Allan D. Spigelman, Desiree du Sart, Kathy Tucker, Judy Kirk. (2001) Hereditary Nonpolyposis Colorectal Cancer in 95 Families: Differences and Similarities between Mutation-Positive and Mutation-Negative Kindreds. The American Journal of Human Genetics 68:1, 118-127
CrossRef111
&NA;. (2000) Social, Ethical and Legal Issues Committee, American College of Medical Genetics. Genetics in Medicine 2:6, 367-368
CrossRef112
Wiljo J. F. de Leeuw, JanWillem Dierssen, Hans F. A. Vasen, Juul Th. Wijnen, Gemma G. Kenter, Hanne Meijers-Heijboer, Annette Brocker-Vriends, Astrid Stormorken, Pal Moller, Fred Menko, Cees J. Cornelisse, Hans Morreau. (2000) Prediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patients. The Journal of Pathology 192:3, 328-335
CrossRef113
Robert E. Schoen. (2000) Families at Risk for Colorectal Cancer. Journal of Clinical Gastroenterology 31:2, 114-120
CrossRef114
Heather Hampel, Paivi Peltomaki. (2000) Hereditary colorectal cancer: risk assessment and management. Clinical Genetics 58:2, 89-97
CrossRef115
Jill E. Stopfer. (2000) Genetic counseling and clinical cancer genetics services. Seminars in Surgical Oncology 18:4, 347-357
CrossRef116
M. Ponz de Leon, L. Roncucci. (2000) The cause of colorectal cancer. Digestive and Liver Disease 32:5, 426-439
CrossRef117
Friedrik P. Wikman, Niels Katballe, Mariann Christensen, Søren Laurberg, Torben F. Ørntoft. (2000) Efficient Mutation Detection in Mismatch Repair Genes Using a Combination of Single-Strand Conformational Polymorphism and Heteroduplex Analysis at a Controlled Temperature. Genetic Testing 4:1, 15-21
CrossRef118
D. Calistri, S. Presciuttini, G. Buonsanti, P. Radice, I. Gazzoli, V. Pensotti, P. Sala, M. Eboli, S. Andreola, A. Russo, M. Pierotti, L. Bertario, G.N. Ranzani. (2000) Microsatellite instability in colorectal-cancer patients with suspected genetic predisposition. International Journal of Cancer 89:1, 87-91
CrossRef119
Tao Liu, Siobhan Wahlberg, Eva Burek, Per Lindblom, Carlos Rubio, Annika Lindblom. (2000) Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer. Genes, Chromosomes and Cancer 27:1, 17-25
CrossRef120
Patrick M. Lynch. (1999) Clinical challenges in management of familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. Cancer 86:S11, 2533-2539
CrossRef121
James F. Helm, Robert S. Sandler. (1999) COLORECTAL CANCER SCREENING. Medical Clinics of North America 83:6, 1403-1422
CrossRef122
Smita Bhatia, Charles B. Pratt, Gerald B. Sharp, Leslie L. Robison. (1999) Family history of cancer in children and young adults with colorectal cancer. Medical and Pediatric Oncology 33:5, 470-475
CrossRef123
Patrick M. Lynch. (1999) Clinical challenges in management of familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. Cancer 86:S8, 1713-1719
CrossRef124
Jonathan P. Terdiman, Peggy G. Conrad, Marvin H. Sleisenger. (1999) Genetic testing in hereditary colorectal cancer: indications and procedures. The American Journal of Gastroenterology 94:9, 2344-2356
CrossRef125
Yun-Qing Bai, Yoshimitsu Akiyama, Hiromi Nagasaki, Shi-Long Lu, Takehiro Arai, Takashi Morisaki, Masatoshi Kitamura, Atsushi Muto, Michio Nagashima, Tadashi Nomizu, Takeo Iwama, Hideaki Itoh, Shozo Baba, Takehisa Iwai, Yasuhito Yuasa. (1999) Predominant germ-line mutation of thehMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds. International Journal of Cancer 82:4, 512-515
CrossRef126
Jae-Gahb Park, Young Jin Park, Juul T. Wijnen, Hans F.A. Vasen. (1999) Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing. International Journal of Cancer 82:4, 516-519
CrossRef127
GJB van Ommen, E Bakker, JT den Dunnen. (1999) The human genome project and the future of diagnostics, treatment, and prevention. The Lancet 354, S5-S10
CrossRef128
Arno G Motulsky. (1999) If I had a gene test, what would I have and who would I tell?. The Lancet 354, S35-S37
CrossRef129
Ilias Scotiniotis, James D. Lewis, Brian L. Strom. (1999) Screening for colorectal cancer and other GI cancers. Current Opinion in Oncology 11:4, 305
CrossRef130
M. Cravo, P. Lage, C. Albuquerque, P. Chaves, I. Claro, T. Gomes, C. Gaspar, P. Fidalgo, J. Soares, C. Nobre-Leit
CrossRef131
H. F. A. Vasen. (1999) P. Meera Khan (1935–1998). Journal of Genetics 78:1, 63-70
CrossRef132
José G. Guillem, Andrew J. Smith, Jorge Puig-La Calle, Leyo Ruo. (1999) Gastrointestinal polyposis syndromes. Current Problems in Surgery 36:4, 217-323
CrossRef133
Randall W. Burt. (1999) Impact of family history on screening and surveillance. Gastrointestinal Endoscopy 49:3, S41-S44
CrossRef134
(1998) Molecular Diagnosis of Hereditary Nonpolyposis Colon Cancer. New England Journal of Medicine 339:13, 924-925
Full Text
