TY - JOUR
T1 - Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT
AU - Larson, Garry P.
AU - Ding, Yan
AU - Cheng, Li S.C.
AU - Lundberg, Cathryn
AU - Gagalang, Virgil
AU - Rivas, Guillermo
AU - Geller, Louis
AU - Weitzel, Jeffrey
AU - MacDonald, Deborah
AU - Archambeau, John
AU - Slater, Jerry
AU - Neuberg, Donna
AU - Daly, Mary B.
AU - Angel, Irene
AU - Benson, Al B.
AU - Smith, Kimberly
AU - Kirkwood, John M.
AU - O'Dwyer, Peter J.
AU - Raskay, Barbara
AU - Sutphen, Rebecca
AU - Drew, Rosalind
AU - Stewart, James A.
AU - Werndli, Jae
AU - Johnson, David
AU - Ruckdeschel, John C.
AU - Elston, Robert C.
AU - Krontiris, Theodore G.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - 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.
AB - 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.
KW - Haplotypes
KW - Chromosomes, Human, Pair 3/genetics
KW - Genetic Predisposition to Disease
KW - Prostatic Neoplasms/genetics
KW - Acid Anhydride Hydrolases/genetics
KW - Humans
KW - Middle Aged
KW - Male
KW - Chromosome Mapping
KW - Case-Control Studies
KW - Neoplasm Proteins/genetics
KW - Aged, 80 and over
KW - Adult
KW - Adenocarcinoma/genetics
KW - Aged
KW - Polymorphism, Single Nucleotide
KW - Genetic Linkage/genetics
KW - Microsatellite Repeats
UR - https://www.scopus.com/pages/publications/13444291029
UR - https://www.scopus.com/pages/publications/13444291029#tab=citedBy
UR - https://www.mendeley.com/catalogue/4458ec19-24bd-3d32-8281-e9ea9a8a3422/
U2 - 10.1158/0008-5472.805.65.3
DO - 10.1158/0008-5472.805.65.3
M3 - Article
C2 - 15705877
SN - 0008-5472
VL - 65
SP - 805
EP - 814
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -