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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
  • Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
    Fehringer G, Kraft P, Pharoah PD, Eeles RA, Chatterjee N, Schumacher FR, Schildkraut JM, Lindström S, Brennan P, Bickeböller H, Houlston RS, Landi MT, Caporaso N, Risch A, Amin Al Olama A, Berndt SI, Giovannucci EL, Grönberg H, Kote-Jarai Z, Ma J, Muir K, Stampfer MJ, Stevens VL, Wiklund F, Willett WC, Goode EL, Permuth JB, Risch HA, Reid BM, Bezieau S, Brenner H, Chan AT, Chang-Claude J, Hudson TJ, Kocarnik JK, Newcomb PA, Schoen RE, Slattery ML, White E, Adank MA, Ahsan H, Aittomäki K, Baglietto L, Blomquist C, Canzian F, Czene K, Dos-Santos-Silva I, Eliassen AH, Figueroa JD, Flesch-Janys D, Fletcher O, Garcia-Closas M, Gaudet MM, Johnson N, Hall P, Hazra A, Hein R, Hofman A, Hopper JL, Irwanto A, Johansson M, Kaaks R, Kibriya MG, Lichtner P, Liu J, Lund E, Makalic E, Meindl A, Müller-Myhsok B, Muranen TA, Nevanlinna H, Peeters PH, Peto J, Prentice RL, Rahman N, Sanchez MJ, Schmidt DF, Schmutzler RK, Southey MC, Tamimi R, Travis RC, Turnbull C, Uitterlinden AG, Wang Z, Whittemore AS, Yang XR, Zheng W, Buchanan DD, Casey G, Conti DV, Edlund CK, Gallinger S, Haile RW, Jenkins M, Le Marchand L, Li L, Lindor NM, Schmit SL, Thibodeau SN, Woods MO, Rafnar T, Gudmundsson J, Stacey SN, Stefansson K, Sulem P, Chen YA, Tyrer JP, Christiani DC, Wei Y, Shen H, Hu Z, Shu XO, Shiraishi K, Takahashi A, Bossé Y, Obeidat M, Nickle D, Timens W, Freedman ML, Li Q, Seminara D, Chanock SJ, Gong J, Peters U, Gruber SB, Amos CI, Sellers TA, Easton DF, Hunter DJ, Haiman CA, Henderson BE, Hung RJ, Ovarian Cancer Association Consortium (OCAC), PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Colorectal Transdisciplinary (CORECT) Study, African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
    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, 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
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
    Wang Z, Zhu B, Zhang M, Parikh H, Jia J, Chung CC, Sampson JN, Hoskins JW, Hutchinson A, Burdette L, Ibrahim A, Hautman C, Raj PS, Abnet CC, Adjei AA, Ahlbom A, Albanes D, Allen NE, Ambrosone CB, Aldrich M, Amiano P, Amos C, Andersson U, Andriole G, Andrulis IL, Arici C, Arslan AA, Austin MA, Baris D, Barkauskas DA, Bassig BA, Beane Freeman LE, Berg CD, Berndt SI, Bertazzi PA, Biritwum RB, Black A, Blot W, Boeing H, Boffetta P, Bolton K, Boutron-Ruault MC, Bracci PM, Brennan P, Brinton LA, Brotzman M, Bueno-de-Mesquita HB, Buring JE, Butler MA, Cai Q, Cancel-Tassin G, Canzian F, Cao G, Caporaso NE, Carrato A, Carreon T, Carta A, Chang GC, Chang IS, Chang-Claude J, Che X, Chen CJ, Chen CY, Chen CH, Chen C, Chen KY, Chen YM, Chokkalingam AP, Chu LW, Clavel-Chapelon F, Colditz GA, Colt JS, Conti D, Cook MB, Cortessis VK, Crawford ED, Cussenot O, Davis FG, De Vivo I, Deng X, Ding T, Dinney CP, Di Stefano AL, Diver WR, Duell EJ, Elena JW, Fan JH, Feigelson HS, Feychting M, Figueroa JD, Flanagan AM, Fraumeni JF, Freedman ND, Fridley BL, Fuchs CS, Gago-Dominguez M, Gallinger S, Gao YT, Gapstur SM, Garcia-Closas M, Garcia-Closas R, Gastier-Foster JM, Gaziano JM, Gerhard DS, Giffen CA, Giles GG, Gillanders EM, Giovannucci EL, Goggins M, Gokgoz N, Goldstein AM, Gonzalez C, Gorlick R, Greene MH, Gross M, Grossman HB, Grubb R, Gu J, Guan P, Haiman CA, Hallmans G, Hankinson SE, Harris CC, Hartge P, Hattinger C, Hayes RB, He Q, Helman L, Henderson BE, Henriksson R, Hoffman-Bolton J, Hohensee C, Holly EA, Hong YC, Hoover RN, Hosgood HD, Hsiao CF, Hsing AW, Hsiung CA, Hu N, Hu W, Hu Z, Huang MS, Hunter DJ, Inskip PD, Ito H, Jacobs EJ, Jacobs KB, Jenab M, Ji BT, Johansen C, Johansson M, Johnson A, Kaaks R, Kamat AM, Kamineni A, Karagas M, Khanna C, Khaw KT, Kim C, Kim IS, Kim JH, Kim YH, Kim YC, Kim YT, Kang CH, Jung YJ, Kitahara CM, Klein AP, Klein R, Kogevinas M, Koh WP, Kohno T, Kolonel LN, Kooperberg C, Kratz CP, Krogh V, Kunitoh H, Kurtz RC, Kurucu N, Lan Q, Lathrop M, Lau CC, Lecanda F, Lee KM, Lee MP, Le Marchand L, Lerner SP, Li D, Liao LM, Lim WY, Lin D, Lin J, Lindstrom S, Linet MS, Lissowska J, Liu J, Ljungberg B, Lloreta J, Lu D, Ma J, Malats N, Mannisto S, Marina N, Mastrangelo G, Matsuo K, McGlynn KA, McKean-Cowdin R, McNeill LH, McWilliams RR, Melin BS, Meltzer PS, Mensah JE, Miao X, Michaud DS, Mondul AM, Moore LE, Muir K, Niwa S, Olson SH, Orr N, Panico S, Park JY, Patel AV, Patino-Garcia A, Pavanello S, Peeters PH, Peplonska B, Peters U, Petersen GM, Picci P, Pike MC, Porru S, Prescott J, Pu X, Purdue MP, Qiao YL, Rajaraman P, Riboli E, Risch HA, Rodabough RJ, Rothman N, Ruder AM, Ryu JS, Sanson M, Schned A, Schumacher FR, Schwartz AG, Schwartz KL, Schwenn M, Scotlandi K, Seow A, Serra C, Serra M, Sesso HD, Severi G, Shen H, Shen M, Shete S, Shiraishi K, Shu XO, Siddiq A, Sierrasesumaga L, Sierri S, Loon Sihoe AD, Silverman DT, Simon M, Southey MC, Spector L, Spitz M, Stampfer M, Stattin P, Stern MC, Stevens VL, Stolzenberg-Solomon RZ, Stram DO, Strom SS, Su WC, Sund M, Sung SW, Swerdlow A, Tan W, Tanaka H, Tang W, Tang ZZ, Tardon A, Tay E, Taylor PR, Tettey Y, Thomas DM, Tirabosco R, Tjonneland A, Tobias GS, Toro JR, Travis RC, Trichopoulos D, Troisi R, Truelove A, Tsai YH, Tucker MA, Tumino R, Van Den Berg D, Van Den Eeden SK, Vermeulen R, Vineis P, Visvanathan K, Vogel U, Wang C, Wang C, Wang J, Wang SS, Weiderpass E, Weinstein SJ, Wentzensen N, Wheeler W, White E, Wiencke JK, Wolk A, Wolpin BM, Wong MP, Wrensch M, Wu C, Wu T, Wu X, Wu YL, Wunder JS, Xiang YB, Xu J, Yang HP, Yang PC, Yatabe Y, Ye Y, Yeboah ED, Yin Z, Ying C, Yu CJ, Yu K, Yuan JM, Zanetti KA, Zeleniuch-Jacquotte A, Zheng W, Zhou B, Mirabello L, Savage SA, Kraft P, Chanock SJ, Yeager M, Landi MT, Shi J, Chatterjee N, Amundadottir LT
    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