Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

Claire L. Simpson, Cheryl D. Cropp, Tiina Wahlfors, Asha George, Marypat S. Jones, Ursula Harper, Damaris Ponciano-Jackson, Teuvo Tammela, Johanna Schleutker, Joan E. Bailey-Wilson

Research output: Contribution to journalArticle

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Abstract

Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (ΔLOD=3.193, empirical P=0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD=2.541, ΔLOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, ΔLOD=2.36, P=0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families.

Original languageEnglish (US)
Pages (from-to)437-443
Number of pages7
JournalEuropean Journal of Human Genetics
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2013

Fingerprint

Genetic Heterogeneity
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 2
Developed Countries
Cause of Death
Lung Neoplasms
Neoplasms
Prostatic Neoplasms
Alleles
Genome
Familial Prostate cancer

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Simpson, C. L., Cropp, C. D., Wahlfors, T., George, A., Jones, M. S., Harper, U., ... Bailey-Wilson, J. E. (2013). Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis. European Journal of Human Genetics, 21(4), 437-443. https://doi.org/10.1038/ejhg.2012.185

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis. / Simpson, Claire L.; Cropp, Cheryl D.; Wahlfors, Tiina; George, Asha; Jones, Marypat S.; Harper, Ursula; Ponciano-Jackson, Damaris; Tammela, Teuvo; Schleutker, Johanna; Bailey-Wilson, Joan E.

In: European Journal of Human Genetics, Vol. 21, No. 4, 01.04.2013, p. 437-443.

Research output: Contribution to journalArticle

Simpson, CL, Cropp, CD, Wahlfors, T, George, A, Jones, MS, Harper, U, Ponciano-Jackson, D, Tammela, T, Schleutker, J & Bailey-Wilson, JE 2013, 'Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis', European Journal of Human Genetics, vol. 21, no. 4, pp. 437-443. https://doi.org/10.1038/ejhg.2012.185
Simpson, Claire L. ; Cropp, Cheryl D. ; Wahlfors, Tiina ; George, Asha ; Jones, Marypat S. ; Harper, Ursula ; Ponciano-Jackson, Damaris ; Tammela, Teuvo ; Schleutker, Johanna ; Bailey-Wilson, Joan E. / Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis. In: European Journal of Human Genetics. 2013 ; Vol. 21, No. 4. pp. 437-443.
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