- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer CenterNCI CANCERLIT® Search: Non-polyposis Colon Cancer, Hereditary - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11112663
AU - Scott RJ; McPhillips M; Meldrum CJ; Fitzgerald PE; Adams K; Spigelman
TI -
AD; du Sart D; Tucker K; Kirk J
Hereditary nonpolyposis colorectal cancer in 95 families: differences
and similarities between mutation-positive and mutation-negative
kindreds.
SO - Am J Hum Genet 2001 Jan;68(1):118-127
AD - Discipline of Medical Genetics, Hunter Area Pathology Service, John
Hunter Hospital, New Lambton, New South Wales, Australia.
rscott@doh.health.nsw.gov.au
Hereditary nonpolyposis colorectal cancer (HNPCC) describes the
condition of a disparate group of families that have in common a
predisposition to colorectal cancer in the absence of a premalignant
phenotype. The genetic basis of this disease has been linked to
mutations in genes associated with DNA mismatch repair. A large
proportion of families harbor changes in one of two genes, hMSH2 and
hMLH1. Approximately 35% of families in which the diagnosis is based on
the Amsterdam criteria do not appear to harbor mutations in
DNA-mismatch-repair genes. In this report we present data from a large
series of families with HNPCC and indicate that there are subtle
differences between families that harbor germline changes in hMSH2 and
families that harbor hMLH1 mutations. Furthermore, there are differences
between the mutation-positive group (hMSH2 and hMLH1 combined) of
families and the mutation-negative group of families. The major findings
identified in this study focus primarily on the extracolonic disease
profile observed between the mutation-positive families and the
mutation-negative families. Breast cancer was not significantly
overrepresented in the hMSH2 mutation-positive group but was
overrepresented in the hMLH1 mutation-positive group and in the
mutation-negative group. Prostate cancer was not overrepresented in the
mutation-positive groups but was overrepresented in the
mutation-negative group. In age at diagnosis of colorectal cancer, there
was no difference between the hMSH2 mutation-positive group and the
hMLH1 mutation-positive group, but there was a significant difference
between these two groups and the mutation-negative group.
2
UI - 11745471
AU - Hemminki K; Li X
TI -
Familial colorectal adenocarcinoma from the Swedish Family-Cancer
Database.
SO - Int J Cancer 2001 Dec 1;94(5):743-8
AD - Department of Biosciences at Novum, Karolinska Institute, Huddinge,
Sweden. kari.hemminki@cnt.ki.se
Familial risks for colorectal (CRC) adenocarcinoma were characterized
from the Swedish Family-Cancer Database covering 9.6 million
individuals, whose family relationships and cancers were obtained from
registered sources, not sensitive to reporting or ascertainment bias.
Cancer cases were retrieved from the Swedish Cancer Registry from years
1958-96. Standardized incidence ratios (SIRs) were calculated based on
gender-, age-, period- and tumor type specific rates. A total of 4,794
and 67,925 CRCs were recorded in offspring and parents, respectively.
For colon and rectal adenocarcinoma, the SIRs in offspring were 2.28 and
1.68 by parental CRC adenocarcinoma, giving attributable proportions of
6.45 and 3.31%, respectively. The SIR of CRC was over 10 when both
offspring and parents were diagnosed at a young age. The risk for
parental CRC adenocarcinoma was over 100 when 2 or more children were
affected. The risk in siblings was also very high when a parent was
affected. The familial cancer sites that associated with CRC were those
typical of hereditary nonpolyposis colorectal cancer (HNPCC). This is
the largest study published on familial CRC and the only one reporting
specifically on adenocarcinoma. The data suggest that HNPCC is the
largest single disease entity among CRCs, probably accounting for less
than 50% of familial CRC. Other familial components appear
heterogeneous, characterized by incomplete penetrance, recessive mode of
inheritance and few associated tumor sites. Copyright 2001 Wiley-Liss,
Inc.
3
UI - 11916155
AU - van Stolk RU
TI -
Familial and inherited colorectal cancer: endoscopic screening and
surveillance.
SO - Gastrointest Endosc Clin N Am 2002 Jan;12(1):111-33
AD - Department of Medicine, Northwestern University School of Medicine,
Chicago, Illinois, USA.
Familial risk of colorectal cancer is very common. The high-risk
inherited syndromes are well described and much is known about the
genetics and the effectiveness of registration, endoscopic surveillance,
and appropriate intervention in these patients. The inherited syndromes,
however, are extremely rare. There is a large group of patients in our
population who can benefit from risk stratification based on the number
of their relatives with colon cancer or adenomas and the age at which
those relatives developed neoplasm. The GI endoscopist has a vital role
in recommending and providing colonoscopic screening for this large
group of patients.
4
UI - 11996796
AU - Planck M; Halvarsson B; Palsson E; Hallen M; Ekelund M; Palsson B;
TI -
Baldetorp B; Nilbert M
Cytogenetic aberrations and heterogeneity of mutations in
repeat-containing genes in a colon carcinoma from a patient with
hereditary nonpolyposis colorectal cancer.
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):46-54
AD - Department of Oncology, University Hospital, 221 85 Lund, Sweden.
maria.planck@onk.lu.se
The majority of tumors from patients affected by hereditary nonpolyposis
colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by
widespread microsatellite instability (MSI) and somatic mutations in
repeated sequences in several cancer-associated genes. An inverse
relationship between MSI and chromosomal instability (CIN) has been
demonstrated and HNPCC-associated tumors are generally characterized by
diploid or near-diploid cells with few or no chromosomal rearrangements.
We have studied MSI, somatic mutations in repeat-containing genes,
DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a
patient with a germline MLH1 mutation. Mutations in coding repeats were
assessed in 10 macroscopically separate areas of the primary tumor and
in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4,
and TGFBRII) showed a consistent lack of mutations, whereas others (BAX,
Caspase-5 and IGFIIR) displayed alterations in some tumor regions but
not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant
karyotype with extra copies of chromosomes 7 and 12 and the structural
aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of
CIN, MSI, and somatic mutations in coding repeats in this tumor suggests
that these phenomena may act together in HNPCC tumorigenesis.
Furthermore, the observed intratumoral heterogeneity of mutations in
coding repeats implies these changes occur late in tumorigenesis and,
thus, probably play a role in tumor progression rather than initiation.
5
UI - 11977532
AU - Katai M; Sakurai A; Fukushima Y
TI -
[Genetic testing and counseling for familial tumor syndromes]
SO - Gan To Kagaku Ryoho 2002 Apr;29(4):502-7
AD - Division of Molecular and Clinical Genetics, Shinshu University
Hospital.
Recent developments in molecular biology have increased our
understanding of the genetics of familial tumor syndromes. Isolation of
the responsible genes has made it possible to identify gene carriers
before they manifest clinical symptoms, which enables early detection of
disease and at times prophylactic surgery. Indications for genetic
testing of susceptible family members, however, should be carefully
considered. Genetic counseling must be provided to clients before
genetic tests. Patients should be provided with the latest knowledge on
the disease and appropriately informed of the benefits and possible
problems associated with genetic test, as such information is essential
for clients to decide whether they will undergo such tests. Genetic
medicine is not sufficiently available at present in Japan.
Establishment of genetic services that deal with genetic counseling,
family support and ethical, social and legal issues is strongly desired.
6
UI - 11977537
AU - Takenoshita S; Takita K
TI -
[Hereditary non-polyposis colorectal cancer (HNPCC)]
SO - Gan To Kagaku Ryoho 2002 Apr;29(4):539-44
AD - Department of Surgery II, Fukushima Medical University, 1 Hikarigaoka,
Fukushima 960-1295, Japan.
Hereditary non-polyposis colorectal cancer (HNPCC) is a type of
hereditary colorectal cancer with autosomal dominant traits. Its causal
genes are mismatch repair genes such as the hMSH2 and hMLH1 genes. Owing
to its frequency, juvenile onset, and the outbreaks of multiple
colorectal cancers and cancers occurring over multiple organs, it is
recognized as a very important disease for the purpose of understanding
not only colorectal cancers, but also other digestive cancers, and
furthering pathological inquiry into the state of cancers in general.
7
UI - 11950865
AU - Albuquerque C; Cravo M; Cruz C; Lage P; Chaves P; Fidalgo P; Suspiro A;
TI -
Nobre Leitao C
Genetic characterisation of patients with multiple colonic polyps.
SO - J Med Genet 2002 Apr;39(4):297-302
8
UI - 11982260
AU - Tinley ST
TI -
Colon cancer in women.
SO - AWHONN Lifelines 2001 Jun-Jul;5(3):26-32
AD - Creighton University, Omaha, Nebraska, USA.
9
UI - 12011148
AU - Hutter P; Wijnen J; Rey-Berthod C; Thiffault I; Verkuijlen P; Farber D;
TI -
Hamel N; Bapat B; Thibodeau SN; Burn J; Wu J; MacNamara E; Heinimann K;
Chong G; Foulkes WD
An MLH1 haplotype is over-represented on chromosomes carrying an HNPCC
predisposing mutation in MLH1.
SO - J Med Genet 2002 May;39(5):323-7
AD - Unit of Genetics, Institut Central des Hopitaux Valaisans, Sion,
Switzerland. pierre.hutter@ichv.vsnet.ch
BACKGROUND: The mismatch repair gene, MLH1, appears to occur as two main
haplotypes at least in white populations. These are referred to as A and
G types with reference to the A/G polymorphism at IVS14-19. On the basis
of preliminary experimental data, we hypothesised that deviations from
the expected frequency of these two haplotypes could exist in carriers
of disease associated MLH1 germline mutations. METHODS: We assembled a
series (n=119) of germline MLH1 mutation carriers in whom phase between
the haplotype and the mutation had been conclusively established.
Controls, without cancer, were obtained from each contributing centre.
Cases and controls were genotyped for the polymorphism in IVS14.
RESULTS: Overall, 66 of 119 MLH1 mutations occurred on a G haplotype
(55.5%), compared with 315 G haplotypes on 804 control chromosomes
(39.2%, p=0.001). The odds ratio (OR) of a mutation occurring on a G
rather than an A haplotype was 1.93 (95% CI 1.29 to 2.91). When we
compared the haplotype frequencies in mutation bearing chromosomes
carried by people of different nationalities with those seen in pooled
controls, all groups showed a ratio of A/G haplotypes that was skewed
towards G, except the Dutch group. On further analysis of the type of
each mutation, it was notable that, compared with control frequencies,
deletion and substitution mutations were preferentially represented on
the G haplotype (p=0.003 and 0.005, respectively). CONCLUSION: We have
found that disease associated mutations in MLH1 appear to occur more
often on one of only two known ancient haplotypes. The underlying reason
for this observation is obscure, but it is tempting to suggest a
possible role of either distant regulatory sequences or of chromatin
structure influencing access to DNA sequence. Alternatively,
differential behaviour of otherwise similar haplotypes should be
considered as prime areas for further study.
10
UI - 12011152
AU - Carayol J; Khlat M; Maccario J; Bonaiti-Pellie C
TI -
Hereditary non-polyposis colorectal cancer: current risks of colorectal
cancer largely overestimated.
SO - J Med Genet 2002 May;39(5):335-9
11
UI - 11967905
AU - Koshiji M; Yonekura Y; Saito T; Yoshioka K
TI -
Microsatellite analysis of fecal DNA for colorectal cancer detection.
SO - J Surg Oncol 2002 May;80(1):34-40
AD - The Second Department of Surgery, Kansai Medical University, Osaka,
Japan. koshiji@takii.kmu.ac.jp
BACKGROUND AND OBJECTIVES: The advent of noninvasive methods of testing
for colorectal cancer that have a high level of specificity and
sensitivity is eagerly awaited. METHODS: Thirty patients with sporadic
colorectal cancer and 11 patients with hereditary nonpolyposis colon
cancer (HNPCC) enrolled in this study. We analyzed the loss of
heterozygosity (LOH) in matched genomic DNA extracted from blood and
surgical specimens (tumor and tumor-free colonic mucosa), and the
corresponding oral rinse and stool specimens using seven microsatellite
loci (APC, p53, DCC, hMLH1, D9S162, D9S171, and IFNA). To reduce the
normal colonocyte DNA contamination of the stool samples, we compared
three different methods for fecal genomic DNA extraction. As normal
controls, we analyzed the LOH using the oral rinse and stool samples
from 15 individuals without cancer. RESULTS: The LOH determined from the
oral rinse and the stool samples matched those determined from the blood
and the neoplastic tissue. All patients with HNPCC had microsatellite
alterations at hMLH-1 in tumor DNA and corresponding fecal DNA. There
were significant differences in the frequency of p53-LOH and D9S171-LOH
between the group with sporadic disease and those with HNSCC (P = 0.0031
and 0.0294, respectively). Two cases with D9S162-LOH were detected in
individuals without cancer. For the patients with sporadic disease,
using p53 and adenomatous polyposis coli (APC), the sensitivity of the
fecal DNA analysis was 96.7% (95% CI, 83-100) with a specificity of
100%. CONCLUSION: We demonstrate that LOH analysis using oral rinse and
stool samples may be a suitable screening tool for colorectal cancer.
Copyright 2002 Wiley-Liss, Inc.
12
UI - 12004844
AU - Fornasarig M; Viel A; Bidoli E; Campagnutta E; Minisini AM; Cannizzaro
TI -
R; Della Puppa L; Boiocchi M
Amsterdam criteria II and endometrial cancer index cases for an accurate
selection of HNPCC families.
SO - Tumori 2002 Jan-Feb;88(1):18-20
AD - Department of Gastroenterology, Centro di Riferimento Oncologico,
Aviano, Italy. mfornasarig@cro.it
Endometrial carcinoma (EC) is the second most common tumor in hereditary
nonpolyposis colorectal cancer (HNPCC), with an incidence rate of 60% by
the age of 70 in mutation carriers. The International Collaborative
Group on HNPCC revised the Amsterdam criteria and proposed a new, wider
definition including extracolonic cancers. The aim of our study was to
evaluate the accuracy of a new definition called Amsterdam criteria II.
We updated, reclassified and compared the pedigrees of 29 women, already
reported as being affected by EC and having a colorectal cancer familial
background, according to the two clinical diagnostic criteria for HNPCC
(Amsterdam criteria I, ACI, and Amsterdam criteria II, ACII) after two
periods of observation (1990-1995 and 1995-2000). According to ACII the
frequency of HNPCC in the population under study increased from 0.9% to
3.7% in the period 1990-1995 and from 3.2% to 3.7% in the period
1995-2000. ACII allowed early detection of HNPCC families and thus made
it possible to provide them with a suitable surveillance program and
genetic testing.
13
UI - 11782355
AU - Shin KH; Shin JH; Kim JH; Park JG
TI -
Mutational analysis of promoters of mismatch repair genes hMSH2 and
hMLH1 in hereditary nonpolyposis colorectal cancer and early onset
colorectal cancer patients: identification of three novel germ-line
mutations in promoter of the hMSH2 gene.
SO - Cancer Res 2002 Jan 1;62(1):38-42
AD - Laboratory of Cell Biology, Cancer Research Institute, Seoul National
University College of Medicine, Seoul 110-744, Korea.
The human DNA mismatch repair genes hMSH2 and hMLH1 are responsible for
the development of hereditary nonpolyposis colorectal cancer (HNPCC).
Although genetic alteration of the coding region of hMSH2 and hMLH1 has
been well investigated in HNPCC patients, the regulatory regions of
these genes have been poorly investigated, though recent studies have
defined and characterized the core promoter regions of hMSH2 and hMLH1.
Therefore, to investigate the presence of germ-line mutations, we
screened the core promoter regions of hMSH2 and hMLH1 from 157
nonmalignant control individuals, 40 cases of HNPCC, 56 suspected HNPCC
cases, and 45 sporadic early onset colorectal cancer patients. Three
novel germ-line mutations of the hMSH2 promoter were identified in two
suspected HNPCC cases and one sporadic early onset colorectal cancer
patient but not in the 157 nonmalignant controls, namely, an A insertion
at position -80, a G-to-A transition at position -190, and a G-to-C
transversion at position -225. Tumors from patients containing the
promoter mutations displayed microsatellite instability. The A insertion
at -80 is within a sequence homologous to the consensus sequence for
E1AF and very close to the major transcription start point. Luciferase
assay demonstrated that the -80A insertion and the -190A allele
decreased the transcriptional efficiency by 82 and 77%, respectively,
and the -225C allele increased the transcriptional efficiency by 466%.
The -80A insertion allele was detected only in affected members within
the family and showed novel transcription factor binding ability.
Furthermore, the loss of single nucleotide polymorphism allelic
expression was identified in blood of the patient containing the -80A
insertion. Our results indicate that mutations in the promoter region of
hMSH2 have a limited role in development of suspected HNPCC and sporadic
early onset colorectal cancer.
14
UI - 11987643
AU - DeDecker L
TI -
When colon cancer runs in the family.
SO - Mich Nurse 2001 Aug;74(7):24, 31
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
