BACKGROUND: Prostate cancer represents a substantial public health burden worldwide. It is the second leading cause of cancer death among men in the United States. A family history of the disease is among the most well-established risk factors for prostate cancer. Efforts to localize prostate cancer susceptibility alleles by using genetic linkage analysis methods have been hindered by genetic heterogeneity, incomplete penetrance, disease phenocopies, and the lack of DNA samples from parents of individuals with late-onset prostate cancer. METHODS: We performed a combined genome-wide linkage analysis among 426 families from four existing hereditary prostate cancer (HPC) study populations to systematically search for prostate cancer susceptibility genes. To decrease the degree of locus heterogeneity, we analyzed subsets of families with similar clinical and demographic characteristics. Nonparametric multipoint linkage was the primary method of analysis. Results are presented as allele-sharing logarithm of the odds (LOD) scores, and all reported P values are two-sided. RESULTS: The strongest evidence for prostate cancer linkage was found at chromosome region 17q22 (nonparametric multipoint Kong and Cox allele-sharing LOD score = 3.16 at marker D17S787; P =.00007). Stratified analyses revealed several additional chromosomal regions that are likely to segregate prostate cancer susceptibility genes among specific subsets of HPC families, including 15q11 among families with late-onset disease (allele-sharing LOD = 5.57 at marker D15S128; P<.00001) and 4q35 among families with four or more affected family members (allele-sharing LOD = 3.10 at marker D4S1615; P =.00008). CONCLUSION: Fine mapping studies to facilitate identification of prostate cancer susceptibility genes in these linked regions are warranted.
BACKGROUND:Prostate cancer represents a substantial public health burden worldwide. It is the second leading cause of cancer death among men in the United States. A family history of the disease is among the most well-established risk factors for prostate cancer. Efforts to localize prostate cancer susceptibility alleles by using genetic linkage analysis methods have been hindered by genetic heterogeneity, incomplete penetrance, disease phenocopies, and the lack of DNA samples from parents of individuals with late-onset prostate cancer. METHODS: We performed a combined genome-wide linkage analysis among 426 families from four existing hereditary prostate cancer (HPC) study populations to systematically search for prostate cancer susceptibility genes. To decrease the degree of locus heterogeneity, we analyzed subsets of families with similar clinical and demographic characteristics. Nonparametric multipoint linkage was the primary method of analysis. Results are presented as allele-sharing logarithm of the odds (LOD) scores, and all reported P values are two-sided. RESULTS: The strongest evidence for prostate cancer linkage was found at chromosome region 17q22 (nonparametric multipoint Kong and Cox allele-sharing LOD score = 3.16 at marker D17S787; P =.00007). Stratified analyses revealed several additional chromosomal regions that are likely to segregate prostate cancer susceptibility genes among specific subsets of HPC families, including 15q11 among families with late-onset disease (allele-sharing LOD = 5.57 at marker D15S128; P<.00001) and 4q35 among families with four or more affected family members (allele-sharing LOD = 3.10 at marker D4S1615; P =.00008). CONCLUSION: Fine mapping studies to facilitate identification of prostate cancer susceptibility genes in these linked regions are warranted.
Authors: Bao-Li Chang; Ethan M Lange; Latchezar Dimitrov; Christopher J Valis; Elizabeth M Gillanders; Leslie A Lange; Kathleen E Wiley; Sarah D Isaacs; Fredrik Wiklund; Agnes Baffoe-Bonnie; Carl D Langefeld; S Lilly Zheng; Mika P Matikainen; Tarja Ikonen; Henna Fredriksson; Teuvo Tammela; Patrick C Walsh; Joan E Bailey-Wilson; Johanna Schleutker; Henrik Gronberg; Kathleen A Cooney; William B Isaacs; Edward Suh; Jeffrey M Trent; Jianfeng Xu Journal: Hum Genet Date: 2005-11-23 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: 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: Ethan M Lange; Lindsey A Ho; Jennifer L Beebe-Dimmer; Yunfei Wang; Elizabeth M Gillanders; Jeffrey M Trent; Leslie A Lange; David P Wood; Kathleen A Cooney Journal: Hum Genet Date: 2006-03-01 Impact factor: 4.132