Genome-Wide Linkage Analysis of 1,233 Prostate Cancer Pedigrees From the International Consortium for Prostate Cancer Genetics Using Novel sum LINK and sum LOD Analyses

被引：23

作者：

Christensen, G. Bryce ^{[1
,2
]}

Baffoe-Bonnie, Agnes B. ^{[3
,4
]}

George, Asha ^{[3
]}

Powell, Isaac ^{[5
]}

Bailey-Wilson, Joan E. ^{[4
]}

Carpten, John D. ^{[6
]}

Giles, Graham G. ^{[7
]}

Hopper, John L. ^{[8
]}

Seven, Gianluca ^{[7
]}

English, Dallas R. ^{[8
]}

Foulkes, William D. ^{[9
]}

Maehle, Lovise ^{[10
]}

Moller, Pal ^{[10
]}

Eeles, Ros ^{[11
]}

Easton, Douglas ^{[12
]}

Badzioch, Michael D. ^{[13
]}

Whittemore, Alice S. ^{[14
,15
]}

Oakley-Girvan, Ingrid ^{[15
]}

Hsieh, Chih-Lin ^{[16
,17
]}

Dimitrov, Latchezar ^{[18
,19
]}

Xu, Jianfeng ^{[18
,19
]}

Stanford, Janet L. ^{[20
]}

Johanneson, Bo ^{[21
]}

Deutsch, Kerry ^{[22
]}

McIntosh, Laura ^{[20
]}

Ostrander, Elaine A. ^{[21
]}

Wiley, Kathleen E. ^{[23
,24
]}

Isaacs, Sarah D. ^{[23
,24
]}

Walsh, Patrick C. ^{[23
,24
]}

Isaacs, William B. ^{[23
,24
]}

Thibodeau, Stephen N. ^{[25
]}

McDonnell, Shannon K. ^{[25
]}

Hebbring, Scott ^{[25
]}

Schaid, Daniel J. ^{[25
]}

Lange, Ethan M. ^{[26
,27
]}

Cooney, Kathleen A. ^{[27
]}

Tammela, Teuvo L. J. ^{[28
,29
]}

Schleutker, Johanna ^{[28
,29
]}

Paiss, Thomas ^{[30
,31
]}

Maier, Christiane ^{[30
,32
]}

Gronberg, Henrik ^{[33
,34
]}

Wiklund, Fredrik ^{[33
,34
]}

Emanuelsson, Monica ^{[33
,35
]}

Farnham, James M. ^{[1
,2
]}

Cannon-Albright, Lisa A. ^{[1
,2
]}

Camp, Nicola J. ^{[1
,2
]}

机构：

[1] Univ Utah, Sch Med, Div Genet Epidemiol, Salt Lake City, UT 84108 USA

[2] Univ Utah, ICPCG Grp, Salt Lake City, UT 84108 USA

[3] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[4] NHGRI, NIH, Bethesda, MD 20892 USA

[5] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[6] Translat Genom Res Inst, Genet Basis Human Dis Res Div, Phoenix, AZ USA

[7] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[8] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[9] McGill Univ, Dept Oncol, Montreal, PQ, Canada

[10] Norwegian Radium Hosp, Oslo, Norway

[11] Royal Marsden NHS Fdn Trust, Inst Canc Res, Surrey, England

[12] Canc Res UK Genet Epidemiol Unit, Cambridge, England

[13] Univ Washington, Med Ctr, Div Med Genet, Seattle, WA 98195 USA

[14] Stanford Sch Med, Dept Hlth Res & Policy, Stanford, CA USA

[15] Stanford Sch Med, Stanford Comprehens Canc Ctr, Stanford, CA USA

[16] Univ So Calif, Dept Urol, Los Angeles, CA USA

[17] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA

[18] Wake Forest Univ, Bowman Gray Sch Med, Data Coordinating Ctr ICPCG, Winston Salem, NC USA

[19] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA

[20] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[21] NIH, Canc Genet Branch, Bethesda, MD 20892 USA

[22] Inst Syst Biol, Seattle, WA USA

[23] Johns Hopkins Univ, ICPCG Grp, Baltimore, MD USA

[24] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA

[25] Mayo Clin, ICPCG Grp, Rochester, MN USA

[26] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[27] Univ Michigan, ICPCG Grp, Ann Arbor, MI 48109 USA

[28] Univ Tampere, ICPCG Grp, FIN-33101 Tampere, Finland

[29] Tampere Univ Hosp, Tampere, Finland

[30] Univ Ulm, ICPCG Grp, Ulm, Germany

[31] Univ Ulm, Dept Urol, Ulm, Germany

[32] Univ Ulm, Inst Human Genet, Ulm, Germany

[33] Umea Univ, ICPCG Grp, Umea, Sweden

[34] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[35] Umea Univ, Ctr Oncol, Umea, Sweden

来源：

PROSTATE | 2010年 / 70卷 / 07期

基金：

芬兰科学院; 美国国家卫生研究院; 英国医学研究理事会;

关键词：

genetic epidemiology; meta analysis; susceptibility; predisposition; cancer; SUSCEPTIBILITY; FAMILIES; LOCI; AGGRESSIVENESS; GENES; SCAN; ASSOCIATION; 22Q12.3; RISK;

D O I：

10.1002/pros.21106

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND. Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS. We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS. Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS. Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735-744, 2010. (C) 2010 Wiley-Liss, Inc.

引用

页码：735 / 744

页数：10

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