Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT

Garry P. Larson, Yan Ding, Li S C Cheng, Cathryn Lundberg, Virgil Gagalang, Guillermo Rivas, Louis Geller, Jeffrey Weitzel, Deborah MacDonald, John Archambeau, Jerry Slater, Donna Neuberg, Mary B. Daly, Irene Angel, Al B. Benson, Kimberly Smith, John M. Kirkwood, Peter J. O'Dwyer, Barbara Raskay, Rebecca Sutphen & 7 others Rosalind Drew, James A. Stewart, Jae Werndli, David Johnson, John C. Ruckdeschel, Robert C. Elston, Theodore G. Krontiris

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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 identily-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 χ2 = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.

Original languageEnglish (US)
Pages (from-to)805-814
Number of pages10
JournalCancer Research
Volume65
Issue number3
StatePublished - Feb 1 2005

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Genetic Linkage
Chromosomes, Human, Pair 3
Introns
Single Nucleotide Polymorphism
Prostatic Neoplasms
Alleles
Genetic Association Studies
Adenocarcinoma
Chromosomes
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Larson, G. P., Ding, Y., Cheng, L. S. C., Lundberg, C., Gagalang, V., Rivas, G., ... Krontiris, T. G. (2005). Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. Cancer Research, 65(3), 805-814.

Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. / Larson, Garry P.; Ding, Yan; Cheng, Li S C; Lundberg, Cathryn; Gagalang, Virgil; Rivas, Guillermo; Geller, Louis; Weitzel, Jeffrey; MacDonald, Deborah; Archambeau, John; Slater, Jerry; Neuberg, Donna; Daly, Mary B.; Angel, Irene; Benson, Al B.; Smith, Kimberly; Kirkwood, John M.; O'Dwyer, Peter J.; Raskay, Barbara; Sutphen, Rebecca; Drew, Rosalind; Stewart, James A.; Werndli, Jae; Johnson, David; Ruckdeschel, John C.; Elston, Robert C.; Krontiris, Theodore G.

In: Cancer Research, Vol. 65, No. 3, 01.02.2005, p. 805-814.

Research output: Contribution to journalArticle

Larson, GP, Ding, Y, Cheng, LSC, Lundberg, C, Gagalang, V, Rivas, G, Geller, L, Weitzel, J, MacDonald, D, Archambeau, J, Slater, J, Neuberg, D, Daly, MB, Angel, I, Benson, AB, Smith, K, Kirkwood, JM, O'Dwyer, PJ, Raskay, B, Sutphen, R, Drew, R, Stewart, JA, Werndli, J, Johnson, D, Ruckdeschel, JC, Elston, RC & Krontiris, TG 2005, 'Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT', Cancer Research, vol. 65, no. 3, pp. 805-814.
Larson GP, Ding Y, Cheng LSC, Lundberg C, Gagalang V, Rivas G et al. Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. Cancer Research. 2005 Feb 1;65(3):805-814.
Larson, Garry P. ; Ding, Yan ; Cheng, Li S C ; Lundberg, Cathryn ; Gagalang, Virgil ; Rivas, Guillermo ; Geller, Louis ; Weitzel, Jeffrey ; MacDonald, Deborah ; Archambeau, John ; Slater, Jerry ; Neuberg, Donna ; Daly, Mary B. ; Angel, Irene ; Benson, Al B. ; Smith, Kimberly ; Kirkwood, John M. ; O'Dwyer, Peter J. ; Raskay, Barbara ; Sutphen, Rebecca ; Drew, Rosalind ; Stewart, James A. ; Werndli, Jae ; Johnson, David ; Ruckdeschel, John C. ; Elston, Robert C. ; Krontiris, Theodore G. / Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. In: Cancer Research. 2005 ; Vol. 65, No. 3. pp. 805-814.
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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.

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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 identily-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 χ2 = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.

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