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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

Publication ,  Journal Article
Bailey-Wilson, JE; Childs, EJ; Cropp, CD; Schaid, DJ; Xu, J; Camp, NJ; Cannon-Albright, LA; Farnham, JM; George, A; Powell, I; Carpten, JD ...
Published in: BMC Med Genet
June 19, 2012

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

Duke Scholars

Published In

BMC Med Genet

DOI

EISSN

1471-2350

Publication Date

June 19, 2012

Volume

13

Start / End Page

46

Location

England

Related Subject Headings

  • Prostatic Neoplasms
  • Microsatellite Repeats
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Linkage
  • Chromosomes, Human, X
  • Alleles
  • 3202 Clinical sciences
 

Citation

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MLA
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Bailey-Wilson, J. E., Childs, E. J., Cropp, C. D., Schaid, D. J., Xu, J., Camp, N. J., … International Consortium for Prostate Cancer Genetics, . (2012). Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families. BMC Med Genet, 13, 46. https://doi.org/10.1186/1471-2350-13-46
Bailey-Wilson, Joan E., Erica J. Childs, Cheryl D. Cropp, Daniel J. Schaid, Jianfeng Xu, Nicola J. Camp, Lisa A. Cannon-Albright, et al. “Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.BMC Med Genet 13 (June 19, 2012): 46. https://doi.org/10.1186/1471-2350-13-46.
Bailey-Wilson JE, Childs EJ, Cropp CD, Schaid DJ, Xu J, Camp NJ, et al. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families. BMC Med Genet. 2012 Jun 19;13:46.
Bailey-Wilson, Joan E., et al. “Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.BMC Med Genet, vol. 13, June 2012, p. 46. Pubmed, doi:10.1186/1471-2350-13-46.
Bailey-Wilson JE, Childs EJ, Cropp CD, Schaid DJ, Xu J, Camp NJ, Cannon-Albright LA, Farnham JM, George A, Powell I, Carpten JD, Giles GG, Hopper JL, Severi G, English DR, Foulkes WD, Mæhle L, Møller P, Eeles R, Easton D, Guy M, Edwards S, Badzioch MD, Whittemore AS, Oakley-Girvan I, Hsieh C-L, Dimitrov L, Stanford JL, Karyadi DM, Deutsch K, McIntosh L, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Thibodeau SN, McDonnell SK, Hebbring S, Lange EM, Cooney KA, Tammela TLJ, Schleutker J, Maier C, Bochum S, Hoegel J, Grönberg H, Wiklund F, Emanuelsson M, Cancel-Tassin G, Valeri A, Cussenot O, Isaacs WB, International Consortium for Prostate Cancer Genetics. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families. BMC Med Genet. 2012 Jun 19;13:46.
Journal cover image

Published In

BMC Med Genet

DOI

EISSN

1471-2350

Publication Date

June 19, 2012

Volume

13

Start / End Page

46

Location

England

Related Subject Headings

  • Prostatic Neoplasms
  • Microsatellite Repeats
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Linkage
  • Chromosomes, Human, X
  • Alleles
  • 3202 Clinical sciences