Multiple loci with different cancer specificities within the 8q24 gene desert

Maya Ghoussaini; Honglin Song; Thibaud Koessler; Ali Amin Al Olama; Zsofia Kote-Jarai; Kristy E. Driver; Karen A. Pooley; Susan J. Ramus; Susanne Krüger Kjaer; Estrid Hogdall; Richard A. DiCioccio; Alice S. Whittemore; Simon A. Gayther; Graham G. Giles; Michelle Guy; Stephen M. Edwards; Jonathan Morrison; Jenny L. Donovan; Freddie C. Hamdy; David P. Dearnaley; Audrey T. Ardern-Jones; Amanda L. Hall; Lynne T. O'Brien; Beatrice N. Gehr-Swain; Rosemary A. Wilkinson; Paul M. Brown; John L. Hopper; David E. Neal; Paul D.P. Pharoah; Bruce A.J. Ponder; Rosalind A. Eeles; Douglas F. Easton; Alison M. Dunning

doi:10.1093/jnci/djn190

Multiple loci with different cancer specificities within the 8q24 gene desert

Maya Ghoussaini, Honglin Song, Thibaud Koessler, Ali Amin Al Olama, Zsofia Kote-Jarai, Kristy E. Driver, Karen A. Pooley, Susan J. Ramus, Susanne Krüger Kjaer, Estrid Hogdall, Richard A. DiCioccio, Alice S. Whittemore, Simon A. Gayther, Graham G. Giles, Michelle Guy, Stephen M. Edwards, Jonathan Morrison, Jenny L. Donovan, Freddie C. Hamdy, David P. DearnaleyAudrey T. Ardern-Jones, Amanda L. Hall, Lynne T. O'Brien, Beatrice N. Gehr-Swain, Rosemary A. Wilkinson, Paul M. Brown, John L. Hopper, David E. Neal, Paul D.P. Pharoah, Bruce A.J. Ponder, Rosalind A. Eeles, Douglas F. Easton, Alison M. Dunning

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Abstract

Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.

Original language	English (US)
Pages (from-to)	962-966
Number of pages	5
Journal	Journal of the National Cancer Institute
Volume	100
Issue number	13
DOIs	https://doi.org/10.1093/jnci/djn190
State	Published - Jul 2008
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/djn190

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Ghoussaini, M., Song, H., Koessler, T., Al Olama, A. A., Kote-Jarai, Z., Driver, K. E., Pooley, K. A., Ramus, S. J., Kjaer, S. K., Hogdall, E., DiCioccio, R. A., Whittemore, A. S., Gayther, S. A., Giles, G. G., Guy, M., Edwards, S. M., Morrison, J., Donovan, J. L., Hamdy, F. C., ... Dunning, A. M. (2008). Multiple loci with different cancer specificities within the 8q24 gene desert. Journal of the National Cancer Institute, 100(13), 962-966. https://doi.org/10.1093/jnci/djn190

Ghoussaini, M, Song, H, Koessler, T, Al Olama, AA, Kote-Jarai, Z, Driver, KE, Pooley, KA, Ramus, SJ, Kjaer, SK, Hogdall, E, DiCioccio, RA, Whittemore, AS, Gayther, SA, Giles, GG, Guy, M, Edwards, SM, Morrison, J, Donovan, JL, Hamdy, FC, Dearnaley, DP, Ardern-Jones, AT, Hall, AL, O'Brien, LT, Gehr-Swain, BN, Wilkinson, RA, Brown, PM, Hopper, JL, Neal, DE, Pharoah, PDP, Ponder, BAJ, Eeles, RA, Easton, DF & Dunning, AM 2008, 'Multiple loci with different cancer specificities within the 8q24 gene desert', Journal of the National Cancer Institute, vol. 100, no. 13, pp. 962-966. https://doi.org/10.1093/jnci/djn190

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title = "Multiple loci with different cancer specificities within the 8q24 gene desert",

abstract = "Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.",

author = "Maya Ghoussaini and Honglin Song and Thibaud Koessler and {Al Olama}, {Ali Amin} and Zsofia Kote-Jarai and Driver, {Kristy E.} and Pooley, {Karen A.} and Ramus, {Susan J.} and Kjaer, {Susanne Kr{\"u}ger} and Estrid Hogdall and DiCioccio, {Richard A.} and Whittemore, {Alice S.} and Gayther, {Simon A.} and Giles, {Graham G.} and Michelle Guy and Edwards, {Stephen M.} and Jonathan Morrison and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Dearnaley, {David P.} and Ardern-Jones, {Audrey T.} and Hall, {Amanda L.} and O'Brien, {Lynne T.} and Gehr-Swain, {Beatrice N.} and Wilkinson, {Rosemary A.} and Brown, {Paul M.} and Hopper, {John L.} and Neal, {David E.} and Pharoah, {Paul D.P.} and Ponder, {Bruce A.J.} and Eeles, {Rosalind A.} and Easton, {Douglas F.} and Dunning, {Alison M.}",

year = "2008",

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doi = "10.1093/jnci/djn190",

language = "English (US)",

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T1 - Multiple loci with different cancer specificities within the 8q24 gene desert

AU - Ghoussaini, Maya

AU - Song, Honglin

AU - Koessler, Thibaud

AU - Al Olama, Ali Amin

AU - Kote-Jarai, Zsofia

AU - Driver, Kristy E.

AU - Pooley, Karen A.

AU - Ramus, Susan J.

AU - Kjaer, Susanne Krüger

AU - Hogdall, Estrid

AU - DiCioccio, Richard A.

AU - Whittemore, Alice S.

AU - Gayther, Simon A.

AU - Giles, Graham G.

AU - Guy, Michelle

AU - Edwards, Stephen M.

AU - Morrison, Jonathan

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Dearnaley, David P.

AU - Ardern-Jones, Audrey T.

AU - Hall, Amanda L.

AU - O'Brien, Lynne T.

AU - Gehr-Swain, Beatrice N.

AU - Wilkinson, Rosemary A.

AU - Brown, Paul M.

AU - Hopper, John L.

AU - Neal, David E.

AU - Pharoah, Paul D.P.

AU - Ponder, Bruce A.J.

AU - Eeles, Rosalind A.

AU - Easton, Douglas F.

AU - Dunning, Alison M.

PY - 2008/7

Y1 - 2008/7

N2 - Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.

AB - Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.

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Multiple loci with different cancer specificities within the 8q24 gene desert

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