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 (delta), 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.
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 (delta), 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.
Authors: E M Lange; H Chen; K Brierley; E E Perrone; C H Bock; E Gillanders; M E Ray; K A Cooney Journal: Clin Cancer Res Date: 1999-12 Impact factor: 12.531
Authors: J Carpten; N Nupponen; S Isaacs; R Sood; C Robbins; J Xu; M Faruque; T Moses; C Ewing; E Gillanders; P Hu; P Bujnovszky; I Makalowska; A Baffoe-Bonnie; D Faith; J Smith; D Stephan; K Wiley; M Brownstein; D Gildea; B Kelly; R Jenkins; G Hostetter; M Matikainen; J Schleutker; K Klinger; T Connors; Y Xiang; Z Wang; A De Marzo; N Papadopoulos; O-P Kallioniemi; R Burk; D Meyers; H Grönberg; P Meltzer; R Silverman; J Bailey-Wilson; P Walsh; W Isaacs; J Trent Journal: Nat Genet Date: 2002-01-22 Impact factor: 38.330
Authors: J T Bergthorsson; G Johannesdottir; A Arason; K R Benediktsdottir; B A Agnarsson; J E Bailey-Wilson; E Gillanders; J Smith; J Trent; R B Barkardottir Journal: Hum Genet Date: 2000-10 Impact factor: 4.132
Authors: I Hovatta; T Varilo; J Suvisaari; J D Terwilliger; V Ollikainen; R Arajärvi; H Juvonen; M L Kokko-Sahin; L Väisänen; H Mannila; J Lönnqvist; L Peltonen Journal: Am J Hum Genet Date: 1999-10 Impact factor: 11.025
Authors: Koichi Nagasaki; Christian Schem; Constantin von Kaisenberg; Marco Biallek; Frank Rösel; Walter Jonat; Nicolai Maass Journal: Int J Cancer Date: 2003-07-01 Impact factor: 7.396
Authors: Sanna Pakkanen; Agnes B Baffoe-Bonnie; Mika P Matikainen; Pasi A Koivisto; Teuvo L J Tammela; Snehal Deshmukh; Liang Ou; Joan E Bailey-Wilson; Johanna Schleutker Journal: Hum Genet Date: 2007-01-03 Impact factor: 4.132
Authors: Brian L Yaspan; Kate M McReynolds; J Bradford Elmore; Joan P Breyer; Kevin M Bradley; Jeffrey R Smith Journal: Hum Genet Date: 2008-03-19 Impact factor: 4.132
Authors: Natalay Kouprina; Nicholas C O Lee; Adam Pavlicek; Alexander Samoshkin; Jung-Hyun Kim; Hee-Sheung Lee; Sudhir Varma; William C Reinhold; John Otstot; Greg Solomon; Sean Davis; Paul S Meltzer; Johanna Schleutker; Vladimir Larionov Journal: Genes Chromosomes Cancer Date: 2012-06-26 Impact factor: 5.006
Authors: Cheryl D Cropp; Claire L Simpson; Tiina Wahlfors; Nati Ha; Asha George; MaryPat S Jones; Ursula Harper; Damaris Ponciano-Jackson; Tiffany A Green; Teuvo L J Tammela; Joan Bailey-Wilson; Johanna Schleutker Journal: Int J Cancer Date: 2011-04-20 Impact factor: 7.396
Authors: Natalay Kouprina; Adam Pavlicek; Vladimir N Noskov; Greg Solomon; John Otstot; William Isaacs; John D Carpten; Jeffrey M Trent; Joanna Schleutker; J Carl Barrett; Jerzy Jurka; Vladimir Larionov Journal: Genome Res Date: 2005-11 Impact factor: 9.043
Authors: Ilir Agalliu; Suzanne M Leanza; Lorie Smith; Jeffrey M Trent; John D Carpten; Joan E Bailey-Wilson; Robert D Burk Journal: Prostate Date: 2010-11-01 Impact factor: 4.104
Authors: Joan E Bailey-Wilson; Erica J Childs; Cheryl D Cropp; Daniel J Schaid; Jianfeng Xu; Nicola J Camp; Lisa A Cannon-Albright; James M Farnham; Asha George; Isaac Powell; John D Carpten; Graham G Giles; John L Hopper; Gianluca Severi; Dallas R English; William D Foulkes; Lovise Mæhle; Pål Møller; Rosalind Eeles; Douglas Easton; Michelle Guy; Steve Edwards; Michael D Badzioch; Alice S Whittemore; Ingrid Oakley-Girvan; Chih-Lin Hsieh; Latchezar Dimitrov; Janet L Stanford; Danielle M Karyadi; Kerry Deutsch; Laura McIntosh; Elaine A Ostrander; Kathleen E Wiley; Sarah D Isaacs; Patrick C Walsh; Stephen N Thibodeau; Shannon K McDonnell; Scott Hebbring; Ethan M Lange; Kathleen A Cooney; Teuvo L J Tammela; Johanna Schleutker; Christiane Maier; Sylvia Bochum; Josef Hoegel; Henrik Grönberg; Fredrik Wiklund; Monica Emanuelsson; Geraldine Cancel-Tassin; Antoine Valeri; Olivier Cussenot; William B Isaacs Journal: BMC Med Genet Date: 2012-06-19 Impact factor: 2.103