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Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

dc.contributor.author Bentley, RC
dc.contributor.author Berchuck, Andrew
dc.contributor.author Clyde, Merlise
dc.contributor.author Iversen, Edwin S
dc.contributor.author Marks, JR
dc.contributor.author Moorman, PG
dc.contributor.author Palmieri, Rachel T
dc.contributor.author Schildkraut, JM
dc.contributor.author Whitaker, Regina
dc.contributor.author Wilson, MA
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:30Z
dc.date.accessioned 2014-06-04T19:57:05Z
dc.date.issued 2010-04-08
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20386703
dc.identifier.uri http://hdl.handle.net/10161/8883
dc.description.abstract BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.
dc.language eng
dc.language.iso en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0010061
dc.relation.replaces http://hdl.handle.net/10161/4535
dc.relation.replaces 10161/4535
dc.subject Bayes Theorem
dc.subject Case-Control Studies
dc.subject Cystadenocarcinoma, Serous
dc.subject DNA Damage
dc.subject DNA Repair
dc.subject Data Collection
dc.subject Female
dc.subject Humans
dc.subject Models, Statistical
dc.subject Neoplasm Invasiveness
dc.subject Ovarian Neoplasms
dc.subject Polymorphism, Single Nucleotide
dc.subject Probability
dc.subject Risk
dc.subject Tumor Suppressor Protein p53
dc.title Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.
dc.title.alternative
dc.type Journal article
dc.description.version Version of Record
duke.date.pubdate 2010-4-8
duke.description.issue 4
duke.description.volume 5
dc.relation.journal Plos One
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20386703
pubs.begin-page e10061
pubs.issue 4
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Community and Family Medicine
pubs.organisational-group Community and Family Medicine, Prevention Research
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Obstetrics and Gynecology
pubs.organisational-group Obstetrics and Gynecology, Gynecologic Oncology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Statistical Science
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203


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