A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2.
Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in approximately 20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Similar familial clusters of colon cancer and early-onset colon adenomas have also been reported. To determine whether such familial aggregations arise by chance or reflect a hereditary colon cancer susceptibility, we conducted a whole genome scan to test for genetic linkage in 53 kindreds in which two or more siblings were affected by age 65 or younger with colon cancer or with advanced colon adenomas that were >1 cm in size or that showed high-grade dysplasia. In this cohort we found genetic linkage of disease (P = 0.00045) to chromosomal region 9q22.2-31.2 in a pattern consistent with autosomal dominant disease alleles. These data suggest that a single locus can contribute to disease susceptibility in a subset of patients with nonsyndromic forms of familial colorectal neoplasia.
Wiesner
Georgia L
GL
Department of Genetics, Center for Human Genetics, Ireland Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Daley
Denise
D
Lewis
Susan
S
Ticknor
Christine
C
Platzer
Petra
P
Lutterbaugh
James
J
MacMillen
Melissa
M
Baliner
Boris
B
Willis
Joseph
J
Elston
Robert C
RC
Markowitz
Sanford D
SD
D000483:Alleles; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003110:Colonic Neoplasms / Q000145:classification / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D035781:Siblings
D005819:Genetic Markers; D004247:DNA