Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT.
We conducted linkage analysis of 80 candidate genes in 201 brother pairs affected with prostatic adenocarcinoma. Markers representing two adjacent candidate genes on chromosome 3p, CDC25A and FHIT, showed suggestive evidence for linkage with single-point identity-by-descent allele-sharing statistics. Fine-structure multipoint linkage analysis yielded a maximum LOD score of 3.17 (P = 0.00007) at D3S1234 within FHIT intron 5. For a subgroup of 38 families in which three or more affected brothers were reported, the LOD score was 3.83 (P = 0.00001). Further analysis reported herein suggested a recessive mode of inheritance. Association testing of 16 single nucleotide polymorphisms (SNP) spanning a 381-kb interval surrounding D3S1234 in 202 cases of European descent with 143 matched, unrelated controls revealed significant evidence for association between case status and the A allele of single nucleotide polymorphism rs760317, located within intron 5 of FHIT (Pearson's chi(2) = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.
Larson
Garry P
GP
Division of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Ding
Yan
Y
Cheng
Li S-C
LS
Lundberg
Cathryn
C
Gagalang
Virgil
V
Rivas
Guillermo
G
Geller
Louis
L
Weitzel
Jeffrey
J
MacDonald
Deborah
D
Archambeau
John
J
Slater
Jerry
J
Neuberg
Donna
D
Daly
Mary B
MB
Angel
Irene
I
Benson
Al B
AB
Smith
Kimberly
K
Kirkwood
John M
JM
O'Dwyer
Peter J
PJ
Raskay
Barbara
B
Sutphen
Rebecca
R
Drew
Rosalind
R
Stewart
James A
JA
Werndli
Jae
J
Johnson
David
D
Ruckdeschel
John C
JC
Elston
Robert C
RC
Krontiris
Theodore G
TG
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase