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

Research output: Contribution to journalArticle

18 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 languageEnglish (US)
Pages (from-to)805-814
Number of pages10
JournalCancer research
Volume65
Issue number3
StatePublished - 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.