A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.
Summary of "A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24."
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.
Affiliation
[1] Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. [2] These authors contributed equally to this work.
Journal Details
This article was published in the following journal.
Name: Nature genetics
ISSN: 1546-1718
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20852632
- DOI: http://dx.doi.org/10.1038/ng.668
Medical and Biotech [MESH] Definitions
Genome-wide Association Study
An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.
Genetic Loci
Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.
Dna Fingerprinting
A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.
Minor Lymphocyte Stimulatory Loci
Genetic loci responsible for the encoding of minor lymphocyte stimulatory antigens. There are at least two unlinked loci (in the mouse) and they appear to be separate from the MAJOR HISTOCOMPATIBILITY COMPLEX and MINOR HISTOCOMPATIBILITY LOCI. The mouse mammary tumor virus (see MAMMARY TUMOR VIRUS, MOUSE) has the ability to integrate into these loci. The antigens induce strong T-cell proliferative responses in mixed lymphocyte reactions.
Retracted Publication
Work consisting of the designation of an article or book as retracted in whole or in part by an author or authors or an authorized representative. It identifies a citation previously published and now retracted through a formal issuance from the author, publisher, or other authorized agent, and is distinguished from RETRACTION OF PUBLICATION, which identifies the citation retracting the original published item.
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