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Principal Investigator
Name
Nicolas Wentzensen MD
Degrees
-
Institution
NCI, DCEG, HREB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2009-0558
Initial CDAS Request Approval
Dec 15, 2009
Title
Markers of susceptibility to ovarian cancer risk and survival in PLCO
Summary
Ovarian cancer is the most fatal gynecological malignancy. Currently, there are no efficient screening strategies and most cases present at advanced disease stages. The etiology of ovarian cancer is poorly understood and only few risk factors have been consistently identified. Ovarian cancer is very heterogeneous; ovarian cancer subtypes were found to be associated with different risk factors and molecular profiles. Tissue-based studies of carcinogenic pathways are hampered by the limited access to cancer precursors and to normal ovarian surface epithelium, the most likely tissue at risk. Recently, large efforts have been made to study ovarian cancer risk associated with common genetic variants to identify new susceptibility loci and carcinogenic pathways associated with ovarian cancer. A recent genome-wide scan has identified the first ovarian cancer susceptibility locus and more genome wide scans are currently planned. Ovarian cancers and controls from PLCO can make an important contribution to genome wide association studies, since they are incident cancers with excellent risk factor data, histological evaluation, and survival data. Beyond contributing cases to large genome wide scans, the unique design of PLCO allows studying the association of confirmed SNPs and top candidates with screening outcomes and tumor phenotypes. In addition to studying risk associated with common genetic variants, we propose to analyze the risk associated with telomere length to follow up a strong association of telomere shortening and ovarian cancer risk we previously observed in a case-control study.
Aims

We propose to study common genetic variants and telomere length variations in relation to ovarian cancer risk and clinical features in PLCO. This project will create a nested case-control study with extracted DNA from buffy coats/buccal cells in the screened and unscreened arms of PLCO that will also be a resource for future DNA-based studies. AIM 1: Augment the ovarian cancer case-control studies nested in PLCO with constitutional DNA and genome-wide SNP and copy number variation data - To extract DNA from buffy coats/ buccal cells to create a resource of DNA from ovarian cancer cases. A large number of controls from other GWAS efforts have extracted DNA and genotyping information available and can be used for our goals. - To perform genotyping of ovarian cancer cases using large genome-wide SNP arrays comparable to those previously used in controls (e.g. the Illumina 660K-Quad) AIM2: Contribute PLCO cases and controls to genome-wide association studies of ovarian cancer to identify common variants associated with ovarian cancer risk and survival - To contribute PLCO cases and controls to current GWAS efforts of ovarian cancer to study ovarian cancer risk - To contribute PLCO cases and controls to current efforts to study common genetic variants associated with ovarian cancer survival - To contribute PLCO cases and controls to consortial studies that follow up on candidate SNPs, including fine mapping and immunohistochemical staining in TMAs AIM3: Analyze SNPs related to screening results in PLCO - To study ultrasound screening results (size of ovaries, cysts) related to genetic status - To study sensitivity of biomarker panels in genetic subgroups AIM4: Study genotype-tumor phenotype associations of ovarian cancer - Both in PLCO and another DCEG study (Polish ovarian cancer case control study), several molecular profiling studies of ovarian cancer are currently under way or being planned. We propose to link genotype information to molecular profiles. AIM5: Study ovarian cancer risk related to telomere length - To analyze the association of telomere shortening with ovarian cancer risk in prediagnostic samples - To study genetic variants of genes involved in telomere biology with telomere length in ovarian cancers and controls

Collaborators

Kelly Bolton (NCI, DCEG)
Stephen Chanock (NCI, DCEG)
Montserrat Garcia-Closas (NCI, DCEG)
Robert Greenlee (Marshfield Clinic)
Patricia Hartge (NCI, DCEG)
Lawrence Ragard (Westat)
Lisa Mirabello (NCI, DCEG)
Saundra Buys (University of Utah/Boise)
Sharon Savage (NCI, DCEG)
Mark Sherman (NCI, DCEG)
Sholom Wacholder (NCI, DCEG)
Nicolas Wentzensen (NCI, DCEG)

Related Publications
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    Cancer Res. 2016; Volume 76 (Issue 17): Pages 5103-14 PUBMED
  • Mosaic 13q14 deletions in peripheral leukocytes of non-hematologic cancer cases and healthy controls.
    Machiela MJ, Zhou W, Caporaso N, Dean M, Gapstur SM, Goldin L, Stevens VL, Yeager M, Chanock SJ
    J. Hum. Genet. 2016 May; Volume 61 (Issue 5): Pages 411-8 PUBMED
  • Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.
    Hung RJ, Ulrich CM, Goode EL, Brhane Y, Muir K, Chan AT, Marchand LL, Schildkraut J, Witte JS, Eeles R, Boffetta P, Spitz MR, Poirier JG, Rider DN, Fridley BL, Chen Z, Haiman C, Schumacher F, Easton DF, Landi MT, ...show more Brennan P, Houlston R, Christiani DC, Field JK, Bickeböller H, Risch A, Kote-Jarai Z, Wiklund F, Grönberg H, Chanock S, Berndt SI, Kraft P, Lindström S, Al Olama AA, Song H, Phelan C, Wentzensen N, Peters U, Slattery ML, GECCO, Sellers TA, FOCI, Casey G, Gruber SB, CORECT, Hunter DJ, DRIVE, Amos CI, Henderson B, GAME-ON Network
    J. Natl. Cancer Inst. 2015 Nov; Volume 107 (Issue 11) PUBMED
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    Hum. Mol. Genet. 2014 Dec; Volume 23 (Issue 24): Pages 6616-33 PUBMED
  • Genetic variation on 9p22 is associated with abnormal ovarian ultrasound results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
    Wentzensen N, Black A, Jacobs K, Yang HP, Berg CD, Caporaso N, Peters U, Ragard L, Buys SS, Chanock S, Hartge P
    PLoS ONE. 2011; Volume 6 (Issue 7): Pages e21731 PUBMED