title: Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT.
abstract: 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.
authors.affiliation: Division of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Larson
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Li S-C
authors.initials: LS
authors.lastname: Cheng
authors.forename: Cathryn
authors.initials: C
authors.lastname: Lundberg
authors.forename: Virgil
authors.initials: V
authors.lastname: Gagalang
authors.forename: Guillermo
authors.initials: G
authors.lastname: Rivas
authors.forename: Louis
authors.initials: L
authors.lastname: Geller
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weitzel
authors.forename: Deborah
authors.initials: D
authors.lastname: MacDonald
authors.forename: John
authors.initials: J
authors.lastname: Archambeau
authors.forename: Jerry
authors.initials: J
authors.lastname: Slater
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Irene
authors.initials: I
authors.lastname: Angel
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Kimberly
authors.initials: K
authors.lastname: Smith
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
authors.forename: Barbara
authors.initials: B
authors.lastname: Raskay
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sutphen
authors.forename: Rosalind
authors.initials: R
authors.lastname: Drew
authors.forename: James A
authors.initials: JA
authors.lastname: Stewart
authors.forename: Jae
authors.initials: J
authors.lastname: Werndli
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: John C
authors.initials: JC
authors.lastname: Ruckdeschel
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Krontiris
mesh_terms: 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
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase