Multiple loci with different cancer specificities within the 8q24 gene desert
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...
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| Vydáno v: | JNCI : Journal of the National Cancer Institute Ročník 100; číslo 13; s. 962 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
02.07.2008
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| ISSN: | 1460-2105, 1460-2105 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
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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. |
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| AbstractList | 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.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. 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 | Ponder, Bruce A J Kote-Jarai, Zsofia Song, Honglin Morrison, Jonathan Easton, Douglas F Whittemore, Alice S Dunning, Alison M Koessler, Thibaud Gehr-Swain, Beatrice N Pooley, Karen A Ghoussaini, Maya Hopper, John L Ardern-Jones, Audrey T Wilkinson, Rosemary A Pharoah, Paul D P Giles, Graham G Guy, Michelle Dearnaley, David P Neal, David E Gayther, Simon A Eeles, Rosalind A Kjaer, Susanne Krüger Driver, Kristy E O'Brien, Lynne T Ramus, Susan J DiCioccio, Richard A Edwards, Stephen M Donovan, Jenny L Hamdy, Freddie C Hall, Amanda L Al Olama, Ali Amin Hogdall, Estrid Brown, Paul M |
| Author_xml | – sequence: 1 givenname: Maya surname: Ghoussaini fullname: Ghoussaini, Maya email: maya@srl.cam.ac.uk organization: Cancer Research UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, CB1 8RN, Cambridge, UK. maya@srl.cam.ac.uk – sequence: 2 givenname: Honglin surname: Song fullname: Song, Honglin – sequence: 3 givenname: Thibaud surname: Koessler fullname: Koessler, Thibaud – sequence: 4 givenname: Ali Amin surname: Al Olama fullname: Al Olama, Ali Amin – sequence: 5 givenname: Zsofia surname: Kote-Jarai fullname: Kote-Jarai, Zsofia – sequence: 6 givenname: Kristy E surname: Driver fullname: Driver, Kristy E – sequence: 7 givenname: Karen A surname: Pooley fullname: Pooley, Karen A – sequence: 8 givenname: Susan J surname: Ramus fullname: Ramus, Susan J – sequence: 9 givenname: Susanne Krüger surname: Kjaer fullname: Kjaer, Susanne Krüger – sequence: 10 givenname: Estrid surname: Hogdall fullname: Hogdall, Estrid – sequence: 11 givenname: Richard A surname: DiCioccio fullname: DiCioccio, Richard A – sequence: 12 givenname: Alice S surname: Whittemore fullname: Whittemore, Alice S – sequence: 13 givenname: Simon A surname: Gayther fullname: Gayther, Simon A – sequence: 14 givenname: Graham G surname: Giles fullname: Giles, Graham G – sequence: 15 givenname: Michelle surname: Guy fullname: Guy, Michelle – sequence: 16 givenname: Stephen M surname: Edwards fullname: Edwards, Stephen M – sequence: 17 givenname: Jonathan surname: Morrison fullname: Morrison, Jonathan – sequence: 18 givenname: Jenny L surname: Donovan fullname: Donovan, Jenny L – sequence: 19 givenname: Freddie C surname: Hamdy fullname: Hamdy, Freddie C – sequence: 20 givenname: David P surname: Dearnaley fullname: Dearnaley, David P – sequence: 21 givenname: Audrey T surname: Ardern-Jones fullname: Ardern-Jones, Audrey T – sequence: 22 givenname: Amanda L surname: Hall fullname: Hall, Amanda L – sequence: 23 givenname: Lynne T surname: O'Brien fullname: O'Brien, Lynne T – sequence: 24 givenname: Beatrice N surname: Gehr-Swain fullname: Gehr-Swain, Beatrice N – sequence: 25 givenname: Rosemary A surname: Wilkinson fullname: Wilkinson, Rosemary A – sequence: 26 givenname: Paul M surname: Brown fullname: Brown, Paul M – sequence: 27 givenname: John L surname: Hopper fullname: Hopper, John L – sequence: 28 givenname: David E surname: Neal fullname: Neal, David E – sequence: 29 givenname: Paul D P surname: Pharoah fullname: Pharoah, Paul D P – sequence: 30 givenname: Bruce A J surname: Ponder fullname: Ponder, Bruce A J – sequence: 31 givenname: Rosalind A surname: Eeles fullname: Eeles, Rosalind A – sequence: 32 givenname: Douglas F surname: Easton fullname: Easton, Douglas F – sequence: 33 givenname: Alison M surname: Dunning fullname: Dunning, Alison M |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18577746$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Contributor | Leung, Hing Herbert, Pippa Lyons, Norma Gillatt, David Kynaston, Howard Elliott, Emma Kockelbergh, Roger Lennon, Teresa Moody, Hilary Holding, Peter Bollina, Prasad Cooper, Debbie Doble, Andrew Prescott, Stephen Durkan, Garett Powell, Philip Howson, Joanne Jones, Mandy Doherty, Alan Thompson, Pauline Bonnington, Sue |
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| DOI | 10.1093/jnci/djn190 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
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| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1460-2105 |
| ExternalDocumentID | 18577746 |
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| Snippet | Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with... |
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| SubjectTerms | Adult Aged Breast Neoplasms - genetics Case-Control Studies Chromosome Mapping Chromosomes, Human, Pair 8 - genetics Colorectal Neoplasms - genetics Female Gene Frequency Genetic Predisposition to Disease Genotype Haplotypes Humans Logistic Models Male Middle Aged Ovarian Neoplasms - genetics Polymorphism, Single Nucleotide Prostatic Neoplasms - genetics |
| Title | Multiple loci with different cancer specificities within the 8q24 gene desert |
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