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; Rosalind Drew; James A. Stewart; Jae Werndli; David Johnson; John C. Ruckdeschel; Robert C. Elston; Theodore G. Krontiris

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 SutphenRosalind Drew, James A. Stewart, Jae Werndli, David Johnson, John C. Ruckdeschel, Robert C. Elston, Theodore G. Krontiris

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19 Scopus citations

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 language	English (US)
Pages (from-to)	805-814
Number of pages	10
Journal	Cancer research
Volume	65
Issue number	3
State	Published - Feb 1 2005

ASJC Scopus subject areas

Oncology
Cancer Research

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Larson, G. P., Ding, Y., Cheng, L. S. C., Lundberg, C., Gagalang, V., Rivas, G., Geller, L., Weitzel, J., MacDonald, D., Archambeau, J., Slater, J., Neuberg, D., Daly, M. B., Angel, I., Benson, A. B., Smith, K., Kirkwood, J. M., O'Dwyer, P. J., Raskay, B., ... Krontiris, T. G. (2005). Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT. Cancer research, 65(3), 805-814.

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.

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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 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.",

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

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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 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.

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

Abstract

ASJC Scopus subject areas

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