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

dc.contributor.author

Schildkraut, Joellen M

dc.contributor.author

Iversen, Edwin S

dc.contributor.author

Wilson, Melanie A

dc.contributor.author

Clyde, Merlise A

dc.contributor.author

Moorman, Patricia G

dc.contributor.author

Palmieri, Rachel T

dc.contributor.author

Whitaker, Regina

dc.contributor.author

Bentley, Rex C

dc.contributor.author

Marks, Jeffrey R

dc.contributor.author

Berchuck, Andrew

dc.contributor.editor

Dubé, Marie-Pierre

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.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.description.version

Version of Record

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20386703

dc.identifier.eissn

1932-6203

dc.identifier.uri

https://hdl.handle.net/10161/8883

dc.language

eng

dc.language.iso

en_US

dc.publisher

Public Library of Science (PLoS)

dc.relation.ispartof

PLoS One

dc.relation.isversionof

10.1371/journal.pone.0010061

dc.relation.journal

Plos One

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

duke.contributor.orcid

Clyde, Merlise A|0000-0002-3595-1872

duke.contributor.orcid

Moorman, Patricia G|0000-0002-2978-6495

duke.contributor.orcid

Bentley, Rex C|0000-0002-4947-9150

duke.contributor.orcid

Marks, Jeffrey R|0000-0002-2054-5468

duke.date.pubdate

2010-4-8

duke.description.issue

4

duke.description.volume

5

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

Files