A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

@article{Goode2010AGA,
  title={A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24},
  author={Ellen L. Goode and Georgia Chenevix-Trench and Honglin Song and Susan J. Ramus and Maria Notaridou and Kate Lawrenson and Martin Widschwendter and Robert A. Vierkant and Melissa C. Larson and Susanne Kr{\"u}ger Kjaer and Michael J. Birrer and Andrew Berchuck and Joellen M Schildkraut and Ian P. M. Tomlinson and Lambertus A.L.M. Kiemeney and Linda S. Cook and Jacek Gronwald and Montserrat Garc{\'i}a-Closas and Martin. E. Gore and Ian G. Campbell and Alice S. Whittemore and Rebecca Sutphen and Catherine M. Phelan and Hoda Anton-Culver and Celeste Leigh Pearce and Diether Lambrechts and Mary Anne Rossing and Jenny Chang-Claude and Kirsten B. Moysich and Marc T. Goodman and Thilo D{\"o}rk and Heli Nevanlinna and Roberta B. Ness and Thorunn Rafnar and Claus K H{\o}gdall and Estrid V. H{\o}gdall and Brooke L. Fridley and Julie M. Cunningham and Weiva Sieh and Valerie McGuire and Andrew K. Godwin and Daniel W. Cramer and Dena G Hernandez and Douglas A. Levine and Karen H. Lu and Edwin S Iversen and Rachel T. Palmieri and Richard S. Houlston and Anne M. van Altena and Katja K. H. Aben and Leon Fag Massuger and Angela R. Brooks-Wilson and Linda E. Kelemen and Nhu D. Le and Anna Jakubowska and Jan Lubiński and Krzysztof Mędrek and Anne Stafford and Douglas F. Easton and Jonathan P. Tyrer and Kelly L. Bolton and Patricia A. Harrington and Diana M. Eccles and Ann Chen and Ashley N Molina and Barbara N Davila and H{\'e}ctor Gustavo Arango and Ya-Yu Tsai and Zhihua Chen and Harvey A. Risch and John R McLaughlin and Steven A. Narod and Argyrios Ziogas and Wendy R. Brewster and Aleksandra Gentry-Maharaj and Usha Menon and Anna H Wu and Daniel O. Stram and Malcolm C. Pike and Jonathan Beesley and Penelope M. Webb},
  journal={Nature Genetics},
  year={2010},
  volume={42},
  pages={874-879}
}
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… 
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References

SHOWING 1-10 OF 33 REFERENCES
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
TLDR
Genetic data provide further evidence for the 'common-disease common-variant' model of CRC predisposition and identify two previously unreported associations.
A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2
TLDR
A genome-wide association study to identify common ovarian cancer susceptibility alleles was performed, identifying 12 SNPs at 9p22 associated with disease risk and the most significant SNP was genotyped in 2,670 ovarian cancer cases and 4,668 controls.
Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21
TLDR
Findings extend the understanding of the role of common genetic variation in CRC etiology by identifying a previously unreported association, rs3802842 on 11q23, and carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC.
Common variants at 19p13 are associated with susceptibility to ovarian cancer
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase
Sequence variant on 8q24 confers susceptibility to urinary bladder cancer
TLDR
No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers.
Identification of a new prostate cancer susceptibility locus on chromosome 8q24
We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association
Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility
TLDR
In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, it is estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.
Multiple loci with different cancer specificities within the 8q24 gene desert.
TLDR
It is concluded that there are at least five separate functional variants in this region that are associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer.
Multiple loci on 8q24 associated with prostate cancer susceptibility
TLDR
Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility and confirmed associations at three previously reported loci.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
TLDR
This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
...
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