| Authors: |
Goode, E. L.; Chenevix-Trench, G.; Song, H.; Ramus, S. J.; Notaridou, M.; Lawrenson, K.; Widschwendter, M.; Vierkant, R. A.; Larson, M. C.; Kjaer, S. K.; Birrer, M. J.; Berchuck, A.; Schildkraut, J.; Tomlinson, I.; Kiemeney, L. A.; Cook, L. S.; Gronwald, J.; Garcia-Closas, M.; Gore, M. E.; Campbell, I.; Whittemore, A. S.; Sutphen, R.; Phelan, C.; Anton-Culver, H.; Pearce, C. L.; Lambrechts, D.; Rossing, M. A.; Chang-Claude, J.; Moysich, K. B.; Goodman, M. T.; Dörk, T.; Nevanlinna, H.; Ness, R. B.; Rafnar, T.; Hogdall, C.; Hogdall, E.; Fridley, B. L.; Cunningham, J. M.; Sieh, W.; McGuire, V.; Godwin, A. K.; Cramer, D. W.; Hernandez, D.; Levine, D.; Lu, K.; Iversen, E. S.; Palmieri, R. T.; Houlston, R.; Van Altena, A. M.; Aben, K. K. H.; Massuger, L. F. A. G.; Brooks-Wilson, A.; Kelemen, L. E.; Le, N. D.; Jakubowska, A.; Lubinski, J.; Medrek, K.; Stafford, A.; Easton, D. F.; Tyrer, J.; Bolton, K. L.; Harrington, P.; Eccles, D.; Chen, A.; Molina, A. N.; Davila, B. N.; Arango, H.; Tsai, Y. Y.; Chen, Z.; Risch, H. A.; McLaughlin, J.; Narod, S. A.; Ziogas, A.; Brewster, W.; Gentry-Maharaj, A.; Menon, U.; Wu, A. H.; Stram, D. O.; Pike, M. C.; Beesley, J.; Webb, P. M.; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Chen, X.; Ekici, A. B.; Thiel, F. C.; Beckmann, M. W.; Yang, H.; Wentzensen, N.; Lissowska, J.; Fasching, P. A.; Despierre, E.; Amant, F.; Vergote, I.; Doherty, J.; Hein, R.; Wang-Gohrke, S.; Lurie, G.; Carney, M. E.; Thompson, P. J.; Runnebaum, I.; Hillemanns, P.; Durst, M.; Antonenkova, N.; Bogdanova, N.; Leminen, A.; Butzow, R.; Heikkinen, T.; Stafansson, K.; Sulem, P.; Besenbacher, S.; Sellers, T. A.; Gayther, S. A.; Pharoah, P. D. P.; for the Ovarian Cancer Association Consortium (OCAC) |
| Article Title: |
A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24 |
| Abstract: |
Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P 10 -4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P -5 × 10 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development. © 2010 Nature America, Inc. All rights reserved. |
| Keywords: |
cancer survival; controlled study; unclassified drug; human cell; major clinical study; overall survival; single nucleotide polymorphism; case-control studies; dna-binding proteins; polymorphism, single nucleotide; clinical trial; histopathology; cancer risk; endometrioid carcinoma; genetic analysis; ovarian neoplasms; cancer susceptibility; genetic predisposition to disease; ovary cancer; tumor markers, biological; chromosome 9p; gene locus; genetic association; genotype; genome-wide association study; homeodomain proteins; chromosomes, human, pair 2; chromosomes, human, pair 8; cancer mortality; ovary; multicenter study; gene identification; myc protein; phosphoproteins; cancer classification; clinical trials, phase i as topic; clinical trials, phase ii as topic; tumor suppressor protein; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; proto-oncogene proteins c-myb; genome, human; mucinous carcinoma; chromosome 8q; protein bnc2; protein hoxd1; protein skap1; protein tiparp; chromosome 2q; chromosome 2q31; chromosome 8q24; chromosome 9p22; mucinous ovary cancer; serous ovary cancer
|
| Journal Title: |
Nature Genetics
|
| Volume: |
42 |
| Issue: |
10 |
| ISSN: |
1061-4036 |
| Publisher: |
Nature Publishing Group
|
| Date Published: |
2010-10-01 |
| Start Page: |
874 |
| End Page: |
879 |
| Language: |
English |
| DOI: |
10.1038/ng.668
|
| PUBMED: |
20852632
|
| PROVIDER: |
scopus
|
| PMCID: |
PMC3020231
|
| DOI/URL: |
|
| Notes: |
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- "Cited By (since 1996): 2"
- "Export Date: 20 April 2011"
- "CODEN: NGENE"
- "Source: Scopus"
|
