A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history.
OBJECTIVE
Adenomatous polyposis of the colon is often secondary to an inherited mutation in adenomatous polyposis coli (APC) gene, however, approximately one third of patients have no family history of the disease. We studied the phenotype and genotype of adenomatous polyposis in patients without a family history.


METHODS
A cohort of 57 unrelated adenomatous polyposis patients were evaluated. Seventeen patients with no family history were compared with 40 patients who had a positive family history of the disease. Family history and medical records were collected and analyzed. Germline APC and Mut Y homologue (MYH) testing was undertaken.


RESULTS
Patients without a family history were diagnosed with polyposis at an older age (41 years vs. 32 years) and presenting more frequently with symptoms (76 vs 20, P < 0.05). The number of colonic polyps and frequency of extracolonic manifestation associated with adenomatous polyposis did not differ between the two groups. APC mutations were detected less frequently among patients without a family history of the disease (4 out of 17 vs 25 out of 40, P=0.007), even among those with greater than 100 colorectal adenomas (4 out of 12 versus 21 out of 29, P=0.03). One homozygous MYH mutation carrier (G382D) was detected among the six patients without a family history and without a germline APC mutation who were tested.


CONCLUSIONS
Adenomatous polyposis patients without a family history are usually diagnosed with symptoms, and at a later age. Phenotypically, they are similar to those with a family history. However, germline APC mutations are detected far less frequently in patients without a family history. A small percentage of these cases may be secondary to biallelic germline MYH mutations.
Truta
Brindusa
B
Department of Medicine, Division of Gastroenterology and the Comprehensive Cancer Center, University of California-San Francisco, 2330 Post Street, San Francisco, CA 94115-1623, USA.
Allen
Brian A
BA
Conrad
Peggy G
PG
Weinberg
Vivian
V
Miller
Glenn A
GA
Pomponio
Rob
R
Lipton
Lara R
LR
Guerra
Germano
G
Tomlinson
Ian P M
IP
Sleisenger
Marvin H
MH
Kim
Young S
YS
Terdiman
Jonathan P
JP
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype