Lu L, Cancel-Tassin G, Valeri A, Cussenot O, Lange EM, Cooney KA, Farnham JM, Camp NJ, Cannon-Albright LA, Tammela TL, Schleutker J, Hoegel J, Herkommer K, Maier C, Vogel W, Wiklund F, Emanuelsson M, Gronberg H, Wiley KE, Isaacs SD, Walsh PC, Helfand BT, Kan D, Catalona WJ, Stanford JL, FitzGerald LM, Johanneson B, Deutsch K, McIntosh L, Ostrander EA, Thibodeau SN, McDonnell SK, Hebbring S, Schaid DJ, Whittemore AS, Oakley-Girvan I, Hsieh CL, Powell I, Bailey-Wilson JE, Cropp CD, Simpson C, Carpten JD, Seminara D, Zheng SL, Xu J, Giles GG, Severi G, Hopper JL, English DR, Foulkes WD, Maehle L, Moller P, Badzioch MD, Edwards S, Guy M, Eeles R, Easton D, Isaacs WB (2012) Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG. Prostate 72:410-426
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.