A major locus for hereditary prostate cancer in Finland

Localization by linkage disequilibrium of a haplotype in the HPCX region

A.B. Baffoe-Bonnie, J.R. Smith, D.A. Stephan, J. Schleutker, J.D. Carpten, T. Kainu, E.M. Gillanders, M. Matikainen, T.M. Teslovich, T. Tammela, R. Sood, A.M. Balshem, S.D. Scarborough, J. Xu, W.B. Isaacs, J.M. Trent, Olli Kallioniemi, J.E. Bailey-Wilson (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

Abstract

Background: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with “no-male-to-male” (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher’s exact P-value of 0.0003 for allele ″180″ of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P=0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms (SNPs) to augment the original markers around DXS1205. Results: Our major finding is that markers extending from ″D3S2390″ to ″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s LD measure (δ), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: ″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.
Original languageEnglish
Pages (from-to)307 - 316
Number of pages10
JournalHuman Genetics
Volume117
Issue number4
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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Linkage Disequilibrium
Finland
Haplotypes
Prostatic Neoplasms
Population Control
Alleles
Single Nucleotide Polymorphism
Western World
Genes
Organism Cloning
Familial Prostate cancer
Incidence
Population
Neoplasms

Cite this

Baffoe-Bonnie, A. B., Smith, J. R., Stephan, D. A., Schleutker, J., Carpten, J. D., Kainu, T., ... Bailey-Wilson, J. E. (2005). A major locus for hereditary prostate cancer in Finland: Localization by linkage disequilibrium of a haplotype in the HPCX region. Human Genetics, 117(4), 307 - 316. https://doi.org/10.1007/s00439-005-1306-z
Baffoe-Bonnie, A.B. ; Smith, J.R. ; Stephan, D.A. ; Schleutker, J. ; Carpten, J.D. ; Kainu, T. ; Gillanders, E.M. ; Matikainen, M. ; Teslovich, T.M. ; Tammela, T. ; Sood, R. ; Balshem, A.M. ; Scarborough, S.D. ; Xu, J. ; Isaacs, W.B. ; Trent, J.M. ; Kallioniemi, Olli ; Bailey-Wilson, J.E. / A major locus for hereditary prostate cancer in Finland : Localization by linkage disequilibrium of a haplotype in the HPCX region. In: Human Genetics. 2005 ; Vol. 117, No. 4. pp. 307 - 316.
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title = "A major locus for hereditary prostate cancer in Finland: Localization by linkage disequilibrium of a haplotype in the HPCX region",
abstract = "Background: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with “no-male-to-male” (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher’s exact P-value of 0.0003 for allele ″180″ of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P=0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms (SNPs) to augment the original markers around DXS1205. Results: Our major finding is that markers extending from ″D3S2390″ to ″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s LD measure (δ), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: ″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.",
author = "A.B. Baffoe-Bonnie and J.R. Smith and D.A. Stephan and J. Schleutker and J.D. Carpten and T. Kainu and E.M. Gillanders and M. Matikainen and T.M. Teslovich and T. Tammela and R. Sood and A.M. Balshem and S.D. Scarborough and J. Xu and W.B. Isaacs and J.M. Trent and Olli Kallioniemi and J.E. Bailey-Wilson",
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Baffoe-Bonnie, AB, Smith, JR, Stephan, DA, Schleutker, J, Carpten, JD, Kainu, T, Gillanders, EM, Matikainen, M, Teslovich, TM, Tammela, T, Sood, R, Balshem, AM, Scarborough, SD, Xu, J, Isaacs, WB, Trent, JM, Kallioniemi, O & Bailey-Wilson, JE 2005, 'A major locus for hereditary prostate cancer in Finland: Localization by linkage disequilibrium of a haplotype in the HPCX region', Human Genetics, vol. 117, no. 4, pp. 307 - 316. https://doi.org/10.1007/s00439-005-1306-z

A major locus for hereditary prostate cancer in Finland : Localization by linkage disequilibrium of a haplotype in the HPCX region. / Baffoe-Bonnie, A.B.; Smith, J.R.; Stephan, D.A.; Schleutker, J.; Carpten, J.D.; Kainu, T.; Gillanders, E.M.; Matikainen, M.; Teslovich, T.M.; Tammela, T.; Sood, R.; Balshem, A.M.; Scarborough, S.D.; Xu, J.; Isaacs, W.B.; Trent, J.M.; Kallioniemi, Olli; Bailey-Wilson, J.E. (Corresponding Author).

In: Human Genetics, Vol. 117, No. 4, 2005, p. 307 - 316.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - A major locus for hereditary prostate cancer in Finland

T2 - Localization by linkage disequilibrium of a haplotype in the HPCX region

AU - Baffoe-Bonnie, A.B.

AU - Smith, J.R.

AU - Stephan, D.A.

AU - Schleutker, J.

AU - Carpten, J.D.

AU - Kainu, T.

AU - Gillanders, E.M.

AU - Matikainen, M.

AU - Teslovich, T.M.

AU - Tammela, T.

AU - Sood, R.

AU - Balshem, A.M.

AU - Scarborough, S.D.

AU - Xu, J.

AU - Isaacs, W.B.

AU - Trent, J.M.

AU - Kallioniemi, Olli

AU - Bailey-Wilson, J.E.

PY - 2005

Y1 - 2005

N2 - Background: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with “no-male-to-male” (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher’s exact P-value of 0.0003 for allele ″180″ of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P=0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms (SNPs) to augment the original markers around DXS1205. Results: Our major finding is that markers extending from ″D3S2390″ to ″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s LD measure (δ), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: ″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.

AB - Background: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with “no-male-to-male” (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher’s exact P-value of 0.0003 for allele ″180″ of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P=0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms (SNPs) to augment the original markers around DXS1205. Results: Our major finding is that markers extending from ″D3S2390″ to ″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s LD measure (δ), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: ″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.

U2 - 10.1007/s00439-005-1306-z

DO - 10.1007/s00439-005-1306-z

M3 - Article

VL - 117

SP - 307

EP - 316

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 4

ER -