HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)
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- 作者：Jianfeng Xu (1) (2)
Ethan M. Lange (3) (4)
Lingyi Lu (1) (2)
Siqun L. Zheng (1) (2)
Zhong Wang (1) (2)
Stephen N. Thibodeau (5) (6)
Lisa A. Cannon-Albright (7) (8)
Craig C. Teerlink (7) (8)
Nicola J. Camp (7) (8)
Anna M. Johnson (3) (9)
Kimberly A. Zuhlke (3) (9)
Janet L. Stanford (10) (11)
Elaine A. Ostrander (10) (12)
Kathleen E. Wiley (13) (14)
Sarah D. Isaacs (13) (14)
Patrick C. Walsh (13) (14)
Christiane Maier (15) (16)
Manuel Luedeke (15) (16)
Walther Vogel (15) (17)
Johanna Schleutker (18) (19) (20)
Tiina Wahlfors (18) (19)
Teuvo Tammela (18) (21)
Daniel Schaid (22) (5)
Shannon K. McDonnell (22) (5)
Melissa S. DeRycke (5) (6)
Geraldine Cancel-Tassin (23) (24)
Olivier Cussenot (23) (50)
Fredrik Wiklund (25) (26)
Henrik Gr?nberg (25) (26)
Ros Eeles (27) (28)
Doug Easton (27) (29)
Zsofia Kote-Jarai (27) (28)
Alice S. Whittemore (30) (31) (32)
Chih-Lin Hsieh (30) (33)
Graham G. Giles (27) (34) (35)
John L. Hopper (27) (34) (35)
Gianluca Severi (27) (34) (35)
William J. Catalona (36) (37)
Diptasri Mandal (38) (39)
Elisa Ledet (38) (39)
William D. Foulkes (27) (40) (51)
Nancy Hamel (27) (40) (51)
Lovise Mahle (27) (41)
Pal Moller (27) (41)
Isaac Powell (42) (43)
Joan E. Bailey-Wilson (42) (44)
John D. Carpten (42) (45)
Daniela Seminara (46)
Kathleen A. Cooney (3) (9)
William B. Isaacs (13) (14) - 刊名：Human Genetics
- 出版年：2013
- 出版时间：January 2013
- 年：2013
- 卷：132
- 期：1
- 页码：5-14
- 全文大小：250KB
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21. Lange EM, Robbins CM, Gillanders EM et al (2007) Fine-mapping the putative chromosome 17q21-2 prostate cancer susceptibility gene to a 10?cM region based on linkage analysis. Hum Genet 121:49-5
22. Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559-75 CrossRef
23. Schaid DJ, Chang BL (2005) Description of the international consortium for prostate cancer genetics, and failure to replicate linkage of hereditary prostate cancer to 20q13. Prostate 63:276-90 CrossRef
24. Sun J, Zheng SL, Wiklund F et al (2008) Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12. Nat Genet 40:1153-155 CrossRef
25. Takata R, Akamatsu S, Kubo M et al (2010) Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat Genet 42:751-54 CrossRef
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32. Yeager M, Chatterjee N, Ciampa J et al (2009) Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat Genet 41:1055-057 CrossRef - 作者单位：Jianfeng Xu (1) (2)
Ethan M. Lange (3) (4)
Lingyi Lu (1) (2)
Siqun L. Zheng (1) (2)
Zhong Wang (1) (2)
Stephen N. Thibodeau (5) (6)
Lisa A. Cannon-Albright (7) (8)
Craig C. Teerlink (7) (8)
Nicola J. Camp (7) (8)
Anna M. Johnson (3) (9)
Kimberly A. Zuhlke (3) (9)
Janet L. Stanford (10) (11)
Elaine A. Ostrander (10) (12)
Kathleen E. Wiley (13) (14)
Sarah D. Isaacs (13) (14)
Patrick C. Walsh (13) (14)
Christiane Maier (15) (16)
Manuel Luedeke (15) (16)
Walther Vogel (15) (17)
Johanna Schleutker (18) (19) (20)
Tiina Wahlfors (18) (19)
Teuvo Tammela (18) (21)
Daniel Schaid (22) (5)
Shannon K. McDonnell (22) (5)
Melissa S. DeRycke (5) (6)
Geraldine Cancel-Tassin (23) (24)
Olivier Cussenot (23) (50)
Fredrik Wiklund (25) (26)
Henrik Gr?nberg (25) (26)
Ros Eeles (27) (28)
Doug Easton (27) (29)
Zsofia Kote-Jarai (27) (28)
Alice S. Whittemore (30) (31) (32)
Chih-Lin Hsieh (30) (33)
Graham G. Giles (27) (34) (35)
John L. Hopper (27) (34) (35)
Gianluca Severi (27) (34) (35)
William J. Catalona (36) (37)
Diptasri Mandal (38) (39)
Elisa Ledet (38) (39)
William D. Foulkes (27) (40) (51)
Nancy Hamel (27) (40) (51)
Lovise Mahle (27) (41)
Pal Moller (27) (41)
Isaac Powell (42) (43)
Joan E. Bailey-Wilson (42) (44)
John D. Carpten (42) (45)
Daniela Seminara (46)
Kathleen A. Cooney (3) (9)
William B. Isaacs (13) (14)
1. Data Coordinating Center for the ICPCG, Wake Forest University School of Medicine, Winston-Salem, NC, USA
2. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
3. University of Michigan ICPCG Group, University of Michigan Medical School, Ann Arbor, MI, USA
4. Departments of Genetics and Biostatistics, University of North Carolina, Chapel Hill, NC, USA
5. Mayo Clinic ICPGC Group, Mayo Clinic, Rochester, MN, USA
6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
7. University of Utah ICPCG Group, University of Utah School of Medicine, Salt Lake City, UT, USA
8. Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
9. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
10. Fred Hutchinson Cancer Research Center (FHCRC) ICPCG Group, Seattle, WA, USA
11. Division of Public Health Sciences, FHCRC, Seattle, WA, USA
12. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
13. Johns Hopkins University ICPCG Group, Baltimore, MD, USA
14. Department of Urology, Johns Hopkins Medical Institutions, Johns Hopkins Hospital, Marburg 115, 600 North Wolfe Street, Baltimore, MD, 21287, USA
15. University of Ulm ICPCG Group, University of Ulm, Ulm, Germany
16. Department of Urology, University of Ulm, Ulm, Germany
17. Institute of Human Genetics, University of Ulm, Ulm, Germany
18. University of Tampere ICPCG Group, University of Tampere and Fimlab Laboratories, Tampere, Finland
19. Institute of Biomedical Technology/BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland
20. Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland
21. Department of Urology, Tampere University Hospital, Tampere, Finland
22. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
23. CeRePP ICPCG Group, Paris, France
24. CeRePP UPMC University, Paris, France
50. Department of Urology, APHP, Hospital Tenon, Paris, France
25. Karolinska ICPCG Group, Karolinska Institutet, Stockholm, Sweden
26. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
27. ACTANE (Anglo/Canadian/Texan/Australian/Norwegian/EU Biomed) Consortium ICPCG Group, Surrey, UK
28. Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK
29. Strangeways Laboratory, Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
30. BC/CA/HI ICPCG Group, Stanford School of Medicine, Stanford, CA, USA
31. Department of Health Research and Policy, Stanford School of Medicine, Stanford, CA, USA
32. Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, CA, USA
33. Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA
34. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
35. Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, Australia
36. Northwestern University ICPCG Group, Chicago, IL, USA
37. Northwestern University Feinberg School of Medicine, Chicago, IL, USA
38. Louisiana State University ICPCG Group, New Orleans, LA, USA
39. Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
40. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, QC, Canada
51. Research Institute of the McGill University Health Centre, Montreal, QC, Canada
41. The Norwegian Radium Hospital, Oslo, Norway
42. African American Hereditary Prostate Cancer ICPCG Group, Detroit, MI, USA
43. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
44. Inherited Disease Research Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
45. Genetic Basis of Human Disease Research Division, Translational Genomics Research Institute, Phoenix, AZ, USA
46. National Cancer Institute, NIH, Bethesda, MD, USA - ISSN：1432-1203
文摘
Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6?%), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51?%) than those without (42 of 137, 30?%), P?=?9.9?×?10? [odds ratio 4.42 (95?% confidence interval 2.56-.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P?=?6.5?×?10?). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95?% of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5?% of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.