Cyclin E Overexpression in Epithelial Ovarian Cancer Characterizes an Etiologic Subgroup

Schildkraut, Joellen M.; Moorman, Patricia G.; Bland, Amy E.; Halabi, Susan; Calingaert, Brian; Whitaker, Regina S.; Lee, Paula S.; Elkins-Williams, Tyler; Bentley, Rex C.; Marks, Jeffrey R.; Berchuck, Andrew

doi:10.1158/1055-9965.epi-07-0596

Cited by 31 publications

(28 citation statements)

References 30 publications

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“…Among those sent study information, the response rate was 64 percent. Although the control response rate is somewhat low, this has not affected associations with established epidemiological risk factors [2], [21]. Additionally, it is unlikely that participation would have been influenced by genotype.…”

Section: Methodsmentioning

confidence: 97%

Association between DNA Damage Response and Repair Genes and Risk of Invasive Serous Ovarian Cancer

et al. 2010

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BackgroundWe 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 FindingsThe 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 ORper allele = 0.69; 95% CI = 0.53–0.91) in CHEK2, rs2078486 (median ORper allele = 1.65; 95% CI = 1.21–2.25) and rs12951053 (median ORper 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/SignificanceBased on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.

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Section: Methodsmentioning

confidence: 97%

Association between DNA Damage Response and Repair Genes and Risk of Invasive Serous Ovarian Cancer

et al. 2010

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“…This report was motivated by results from three independent discovery studies focusing on TP53 polymorphisms and risk of ovarian cancer: the North Carolina Ovarian Cancer Study (NCOCS),(21) the Mayo Clinic Case-Control Study (MAYO),(22) and the Polish Ovarian Cancer Study (POCS). (23) The NCOCS and the MAYO utilized a tagSNP approach while the POCS used re-sequencing data to assess common genetic variation in TP53 and two flanking genes in linkage disequilibrium (LD)(24) in invasive ovarian cancer cases and population controls.…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer

Schildkraut¹,

Goode²,

Clyde³

et al. 2009

Cancer Research

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The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP) in the TP53 region. Significant findings from this discovery phase were followed up for replication in the other OCAC studies. Mixed effects logistic regression was used to generate posterior median per allele odds ratios (OR), 95% probability intervals (PI), and Bayes factors (BF) for genotype associations. Five SNPs showed significant associations with risk in one or more of the discovery investigations and were followed up by OCAC. Mixed effects analysis confirmed associations with serous invasive cancers for two correlated (r 2 = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI,

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“…DNA was obtained from over 98% of participants. Further details of the study have been described elsewhere (15). All participants signed informed consent forms and approval for the study was obtained from the Duke University Medical Center Institutional Review Board, participating hospitals, and the human subjects committee at the NC Central Cancer Registry.…”

Section: Methodsmentioning

confidence: 99%

Polymorphism in theIL18Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women

Palmieri¹,

Wilson²,

Iversen³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether lowpenetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a <25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567 -72)

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Cyclin E Overexpression in Epithelial Ovarian Cancer Characterizes an Etiologic Subgroup

Cited by 31 publications

References 30 publications

Association between DNA Damage Response and Repair Genes and Risk of Invasive Serous Ovarian Cancer

Association between DNA Damage Response and Repair Genes and Risk of Invasive Serous Ovarian Cancer

Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer

Polymorphism in theIL18Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women

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