Advertisement

Abstract

Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.

Get full access to this article

View all available purchase options and get full access to this article.

Already a subscriber or AAAS Member?

References

AALTONEN, L.A., CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER, SCIENCE 260: 812 (1993).
ARMSTRONG, B, ENVIRONMENTAL FACTORS AND CANCER INCIDENCE AND MORTALITY IN DIFFERENT COUNTRIES, WITH SPECIAL REFERENCE TO DIETARY PRACTICES, INTERNATIONAL JOURNAL OF CANCER 15: 617 (1975).
DONISKELLER, H, A GENETIC-LINKAGE MAP OF THE HUMAN GENOME, CELL 51: 319 (1987).
FEARON, E.R., A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS, CELL 61: 759 (1990).
GRODEN, J, IDENTIFICATION AND CHARACTERIZATION OF THE FAMILIAL ADENOMATOUS POLYPOSIS-COLI GENE, CELL 66: 589 (1991).
HAKALA, T, ENDOMETRIAL CARCINOMA IN THE CANCER FAMILY SYNDROME, CANCER 68: 1656 (1991).
HOULSTON, R.S., DOMINANT GENES FOR COLORECTAL-CANCER ARE NOT RARE, ANNALS OF HUMAN GENETICS 56: 99 (1992).
JARVINEN, H.J., EPIDEMIOLOGY OF FAMILIAL ADENOMATOUS POLYPOSIS IN FINLAND - IMPACT OF FAMILY SCREENING ON THE COLORECTAL-CANCER RATE AND SURVIVAL, GUT 33: 357 (1992).
JASS, J.R., EVOLUTION OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER, GUT 33: 783 (1992).
JOSLYN, G, IDENTIFICATION OF DELETION MUTATIONS AND 3 NEW GENES AT THE FAMILIAL POLYPOSIS LOCUS, CELL 66: 601 (1991).
KEE, F, HOW PREVALENT IS CANCER FAMILY SYNDROME, GUT 32: 509 (1991).
KINZLER, K.W., IDENTIFICATION OF FAP LOCUS GENES FROM CHROMOSOME-5Q21, SCIENCE 253: 661 (1991).
KNUDSON, A.G., HEREDITARY CANCER, ONCOGENES, AND ANTIONCOGENES, CANCER RESEARCH 45: 1437 (1985).
Lathrop, G. M., Proceedings of the National Academy of Sciences of the United States of America 81: 3443 (1984).
LYNCH, H.T., HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (LYNCH SYNDROME-I AND SYNDROME-II .2. BIOMARKER STUDIES, CANCER 56: 939 (1985).
LYNCH, H.T., HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (LYNCH SYNDROME-I AND SYNDROME-II) - GENETICS, PATHOLOGY, NATURAL-HISTORY, AND CANCER CONTROL .1., CANCER GENETICS AND CYTOGENETICS 53: 143 (1991).
MECKLIN, J.P., TUMOR SPECTRUM IN CANCER FAMILY SYNDROME (HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER), CANCER 68: 1109 (1991).
MECKLIN, J.P., FREQUENCY OF HEREDITARY COLORECTAL-CARCINOMA, GASTROENTEROLOGY 93: 1021 (1987).
Mulvihill, J. J., Prevention of Hereditary Large Bowel Cancer: 61 (1983).
NISHISHO, I, MUTATIONS OF CHROMOSOME-5Q21 GENES IN FAP AND COLORECTAL-CANCER PATIENTS, SCIENCE 253: 665 (1991).
PAKSTIS, A. J., CYTOGENETICS AND CELL GENETICS 51: 1057 (1989).
PELTOMAKI, P, EVIDENCE SUPPORTING EXCLUSION OF THE DCC GENE AND A PORTION OF CHROMOSOME-18Q AS THE LOCUS FOR SUSCEPTIBILITY TO HEREDITARY NONPOLYPOSIS COLORECTAL-CARCINOMA IN 5 KINDREDS, CANCER RESEARCH 51: 4135 (1991).
PELTOMAKI, P, EVIDENCE THAT THE MCC-APC GENE REGION IN 5Q21 IS NOT THE SITE FOR SUSCEPTIBILITY TO HEREDITARY NONPOLYPOSIS COLORECTAL-CARCINOMA, CANCER RESEARCH 52: 4530 (1992).
SHILOH, Y, 2 RFLPS IDENTIFIED BY A HUMAN-CHROMOSOME =2 CLONE AT 2P15-2P16 (HGM8 ASSIGNMENT NO-D2S5), NUCLEIC ACIDS RESEARCH 13: 5403 (1985).
STANBRIDGE, E.J., HUMAN TUMOR SUPPRESSOR GENES, ANNUAL REVIEW OF GENETICS 24: 615 (1990).
VASEN, H. F. A., DISEASES OF THE COLON & RECTUM 34: 424 (1991).
WARTHIN, A.S., Heredity with reference to carcinoma - As shown by the study of the cases examined in the Pathological Laboratory of the University of Michigan, 1895-1913, ARCHIVES OF INTERNAL MEDICINE 12: 546 (1913).
WEBER, J.L., ABUNDANT CLASS OF HUMAN DNA POLYMORPHISMS WHICH CAN BE TYPED USING THE POLYMERASE CHAIN-REACTION, AMERICAN JOURNAL OF HUMAN GENETICS 44: 388 (1989).
WEINBERG, R.A., TUMOR SUPPRESSOR GENES, SCIENCE 254: 1138 (1991).
WEISSENBACH, J, A 2ND-GENERATION LINKAGE MAP OF THE HUMAN GENOME, NATURE 359: 794 (1992).
WILLETT, W, THE SEARCH FOR THE CAUSES OF BREAST AND COLON CANCER, NATURE 338: 389 (1989).
WILLETT, W.C., DIET AND CANCER - AN OVERVIEW .2., NEW ENGLAND JOURNAL OF MEDICINE 310: 697 (1984).

Information & Authors

Information

Published In

Science
Volume 260 | Issue 5109
7 May 1993

Submission history

Published in print: 7 May 1993

Permissions

Request permissions for this article.

Authors

Affiliations

Päivi Peltomäki
Department of Medical Genetics, University of Helsinki, SF-00014 Helsinki, Finland.
Lauri A. Aaltonen
Department of Medical Genetics, University of Helsinki, SF-00014 Helsinki, Finland.
Pertti Sistonen
Department of Medical Sciences, University of Helsinki, and Finnish Red Cross Blood Transfusion Service, SF-00310 Helsinki, Finland.
Lea Pylkkänen
Department of Medical Genetics, University of Helsinki, SF-00014 Helsinki, Finland.
Jukka-Pekka Mecklin
Department of Surgery, Jyväskylä Central Hospital, SF-40620 Jyvaskyla, Finland.
Heikki Järvinen
Second Department of Surgery, Helsinki University Central Hospital, SF-00290 Helsinki, Finland.
Jane S. Green
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1 B 3V6.
Jeremy R. Jass
Department of Pathology, University of Auckland School of Medicine, Auckland, New Zealand.
James L. Weber
Marshfield Medical Research Foundation, Marshfield, Wl 54449.
Fredrick S. Leach
Departments of Oncology, Pathology, and Epidemiology, Johns Hopkins University School of Medicine and School of Public Health and Hygiene, and Johns Hopkins Hospital, Baltimore, MD 21231.
Gloria M. Petersen
Departments of Oncology, Pathology, and Epidemiology, Johns Hopkins University School of Medicine and School of Public Health and Hygiene, and Johns Hopkins Hospital, Baltimore, MD 21231.
Stanley R. Hamilton
Departments of Oncology, Pathology, and Epidemiology, Johns Hopkins University School of Medicine and School of Public Health and Hygiene, and Johns Hopkins Hospital, Baltimore, MD 21231.
Albert de la Chapelle
Department of Medical Genetics, University of Helsinki, SF-00014 Helsinki, Finland.
Bert Vogelstein
Departments of Oncology, Pathology, and Epidemiology, Johns Hopkins University School of Medicine and School of Public Health and Hygiene, and Johns Hopkins Hospital, Baltimore, MD 21231.

Metrics & Citations

Metrics

Article Usage
Altmetrics

Citations

Export citation

Select the format you want to export the citation of this publication.

Cited by

  1. Mismatch Repair Deficiency in Phenotypically Normal Human Cells, Science, 268, 5211, (738-740), (1995)./doi/10.1126/science.7632227
    Abstract
  2. Binding of Mismatched Microsatellite DNA Sequences by the Human MSH2 Protein, Science, 266, 5189, (1403-1405), (1994)./doi/10.1126/science.7973733
    Abstract
  3. Mutation of a mutL Homolog in Hereditary Colon Cancer, Science, 263, 5153, (1625-1629), (1994)./doi/10.1126/science.8128251
    Abstract
  4. DNA Repair Comes Into Its Own, Science, 266, 5186, (728-730), (1994)./doi/10.1126/science.7973626
    Abstract
  5. Gene Defect Identified in Common Hereditary Colon Cancer, Science, 262, 5140, (1645-1645), (1993)./doi/10.1126/science.8259507
    Abstract
  6. Clues to the Pathogenesis of Familial Colorectal Cancer, Science, 260, 5109, (812-816), (1993)./doi/10.1126/science.8484121
    Abstract
  7. New Colon Cancer Gene Discovered, Science, 260, 5109, (751-752), (1993)./doi/10.1126/science.8484115
    Abstract
Loading...

View Options

Get Access

Log in to view the full text

AAAS ID LOGIN

AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Log in via OpenAthens.
Log in via Shibboleth.
More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

View options

PDF format

Download this article as a PDF file

Download PDF

Media

Figures

Multimedia

Tables

Share

Share

Share article link

Share on social media