Abstract
BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 410-426 |
| Number of pages | 17 |
| Journal | Prostate |
| Volume | 72 |
| Issue number | 4 |
| DOIs | |
| State | Published - Mar 2012 |
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Keywords
- 8q24
- hereditary
- prostate cancer
- susceptibility
ASJC Scopus subject areas
- Urology
- Oncology
Cite this
Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG. / Lu, Lingyi; Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier; Lange, Ethan M.; Cooney, Kathleen A.; Farnham, James M.; Camp, Nicola J.; Cannon-Albright, Lisa A.; Tammela, Teuvo L J; Schleutker, Johanna; Hoegel, Josef; Herkommer, Kathleen; Maier, Christiane; Vogel, Walther; Wiklund, Fredrik; Emanuelsson, Monica; Grönberg, Henrik; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Helfand, Brian T.; Kan, Donghui; Catalona, William J.; Stanford, Janet L.; Fitzgerald, Liesel M.; Johanneson, Bo; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A.; Thibodeau, Stephen N; McDonnell, Shannon K.; Hebbring, Scott; Schaid, Daniel J; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih Lin; Powell, Isaac; Bailey-Wilson, Joan E.; Cropp, Cheryl D.; Simpson, Claire; Carpten, John D.; Seminara, Daniela; Zheng, S. Lilly; Xu, Jianfen; Giles, Graham G.; Severi, Gianluca; Hopper, John L.; English, Dallas R.; Foulkes, William D.; Maehle, Lovise; Moller, Pal; Badzioch, Michael D.; Edwards, Steve; Guy, Michelle; Eeles, Ros; Easton, Douglas; Isaacs, William B.
In: Prostate, Vol. 72, No. 4, 03.2012, p. 410-426.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
AU - Lu, Lingyi
AU - Cancel-Tassin, Geraldine
AU - Valeri, Antoine
AU - Cussenot, Olivier
AU - Lange, Ethan M.
AU - Cooney, Kathleen A.
AU - Farnham, James M.
AU - Camp, Nicola J.
AU - Cannon-Albright, Lisa A.
AU - Tammela, Teuvo L J
AU - Schleutker, Johanna
AU - Hoegel, Josef
AU - Herkommer, Kathleen
AU - Maier, Christiane
AU - Vogel, Walther
AU - Wiklund, Fredrik
AU - Emanuelsson, Monica
AU - Grönberg, Henrik
AU - Wiley, Kathleen E.
AU - Isaacs, Sarah D.
AU - Walsh, Patrick C.
AU - Helfand, Brian T.
AU - Kan, Donghui
AU - Catalona, William J.
AU - Stanford, Janet L.
AU - Fitzgerald, Liesel M.
AU - Johanneson, Bo
AU - Deutsch, Kerry
AU - McIntosh, Laura
AU - Ostrander, Elaine A.
AU - Thibodeau, Stephen N
AU - McDonnell, Shannon K.
AU - Hebbring, Scott
AU - Schaid, Daniel J
AU - Whittemore, Alice S.
AU - Oakley-Girvan, Ingrid
AU - Hsieh, Chih Lin
AU - Powell, Isaac
AU - Bailey-Wilson, Joan E.
AU - Cropp, Cheryl D.
AU - Simpson, Claire
AU - Carpten, John D.
AU - Seminara, Daniela
AU - Zheng, S. Lilly
AU - Xu, Jianfen
AU - Giles, Graham G.
AU - Severi, Gianluca
AU - Hopper, John L.
AU - English, Dallas R.
AU - Foulkes, William D.
AU - Maehle, Lovise
AU - Moller, Pal
AU - Badzioch, Michael D.
AU - Edwards, Steve
AU - Guy, Michelle
AU - Eeles, Ros
AU - Easton, Douglas
AU - Isaacs, William B.
PY - 2012/3
Y1 - 2012/3
N2 - BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.
AB - BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.
KW - 8q24
KW - hereditary
KW - prostate cancer
KW - susceptibility
UR - http://www.scopus.com/inward/record.url?scp=84856037428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856037428&partnerID=8YFLogxK
U2 - 10.1002/pros.21443
DO - 10.1002/pros.21443
M3 - Article
C2 - 21748754
AN - SCOPUS:84856037428
VL - 72
SP - 410
EP - 426
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 4
ER -