Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

Kristin L. White, Robert A. Vierkant, Zachary C. Fogarty, Bridget Charbonneau, Matthew S. Block, Paul D P Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne Kruger Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas WentzensenJolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie Bean, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas Du Bois, Ira Schwaab, Claus K. Hogdall, Lene Lundvall, Sara H. Olson, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Ursula Eilber, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Izabela Ziolkowska-Seta, Louise Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van DenBerg, Kathryn L. Terry, Allison F. Vitonis, Jennifer A. Doherty, Sharon E. Johnatty, Anna DeFazio, Honglin Song, Jonathan Tyrer, Thomas A. Sellers, Catherine M. Phelan, Kimberly R. Kalli, Julie M. Cunningham, Brooke L. Fridley, Ellen L. Goode

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome,weevaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-92.

Original languageEnglish (US)
Pages (from-to)987-992
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Ovarian Neoplasms
Single Nucleotide Polymorphism
Recurrence
Survival
Interleukin-18
Genetic Association Studies
Tumor Biomarkers
Proportional Hazards Models
Mitosis
Genotype
Inflammation
Pharmaceutical Preparations
Genes
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome. / White, Kristin L.; Vierkant, Robert A.; Fogarty, Zachary C.; Charbonneau, Bridget; Block, Matthew S.; Pharoah, Paul D P; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel W.; Pearce, Celeste Leigh; Schildkraut, Joellen M.; Menon, Usha; Kjaer, Susanne Kruger; Levine, Douglas A.; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S.; Karlan, Beth Y.; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Fasching, Peter A.; Campbell, Ian; Goodman, Marc T.; Pejovic, Tanja; Bean, Yukie; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif B.; Paul, James; Brown, Robert; Flanagan, James M.; Harter, Philipp; Du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K.; Lundvall, Lene; Olson, Sara H.; Orlow, Irene; Paddock, Lisa E.; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Ziolkowska-Seta, Izabela; Brinton, Louise; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H.; Pike, Malcolm C.; Van DenBerg, David; Terry, Kathryn L.; Vitonis, Allison F.; Doherty, Jennifer A.; Johnatty, Sharon E.; DeFazio, Anna; Song, Honglin; Tyrer, Jonathan; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Cunningham, Julie M.; Fridley, Brooke L.; Goode, Ellen L.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 5, 05.2013, p. 987-992.

Research output: Contribution to journalArticle

White, KL, Vierkant, RA, Fogarty, ZC, Charbonneau, B, Block, MS, Pharoah, PDP, Chenevix-Trench, G, Rossing, MA, Cramer, DW, Pearce, CL, Schildkraut, JM, Menon, U, Kjaer, SK, Levine, DA, Gronwald, J, Culver, HA, Whittemore, AS, Karlan, BY, Lambrechts, D, Wentzensen, N, Kupryjanczyk, J, Chang-Claude, J, Bandera, EV, Hogdall, E, Heitz, F, Kaye, SB, Fasching, PA, Campbell, I, Goodman, MT, Pejovic, T, Bean, Y, Lurie, G, Eccles, D, Hein, A, Beckmann, MW, Ekici, AB, Paul, J, Brown, R, Flanagan, JM, Harter, P, Du Bois, A, Schwaab, I, Hogdall, CK, Lundvall, L, Olson, SH, Orlow, I, Paddock, LE, Rudolph, A, Eilber, U, Dansonka-Mieszkowska, A, Rzepecka, IK, Ziolkowska-Seta, I, Brinton, L, Yang, H, Garcia-Closas, M, Despierre, E, Lambrechts, S, Vergote, I, Walsh, C, Lester, J, Sieh, W, McGuire, V, Rothstein, JH, Ziogas, A, Lubiński, J, Cybulski, C, Menkiszak, J, Jensen, A, Gayther, SA, Ramus, SJ, Gentry-Maharaj, A, Berchuck, A, Wu, AH, Pike, MC, Van DenBerg, D, Terry, KL, Vitonis, AF, Doherty, JA, Johnatty, SE, DeFazio, A, Song, H, Tyrer, J, Sellers, TA, Phelan, CM, Kalli, KR, Cunningham, JM, Fridley, BL & Goode, EL 2013, 'Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 5, pp. 987-992. https://doi.org/10.1158/1055-9965.EPI-13-0028
White, Kristin L. ; Vierkant, Robert A. ; Fogarty, Zachary C. ; Charbonneau, Bridget ; Block, Matthew S. ; Pharoah, Paul D P ; Chenevix-Trench, Georgia ; Rossing, Mary Anne ; Cramer, Daniel W. ; Pearce, Celeste Leigh ; Schildkraut, Joellen M. ; Menon, Usha ; Kjaer, Susanne Kruger ; Levine, Douglas A. ; Gronwald, Jacek ; Culver, Hoda Anton ; Whittemore, Alice S. ; Karlan, Beth Y. ; Lambrechts, Diether ; Wentzensen, Nicolas ; Kupryjanczyk, Jolanta ; Chang-Claude, Jenny ; Bandera, Elisa V. ; Hogdall, Estrid ; Heitz, Florian ; Kaye, Stanley B. ; Fasching, Peter A. ; Campbell, Ian ; Goodman, Marc T. ; Pejovic, Tanja ; Bean, Yukie ; Lurie, Galina ; Eccles, Diana ; Hein, Alexander ; Beckmann, Matthias W. ; Ekici, Arif B. ; Paul, James ; Brown, Robert ; Flanagan, James M. ; Harter, Philipp ; Du Bois, Andreas ; Schwaab, Ira ; Hogdall, Claus K. ; Lundvall, Lene ; Olson, Sara H. ; Orlow, Irene ; Paddock, Lisa E. ; Rudolph, Anja ; Eilber, Ursula ; Dansonka-Mieszkowska, Agnieszka ; Rzepecka, Iwona K. ; Ziolkowska-Seta, Izabela ; Brinton, Louise ; Yang, Hannah ; Garcia-Closas, Montserrat ; Despierre, Evelyn ; Lambrechts, Sandrina ; Vergote, Ignace ; Walsh, Christine ; Lester, Jenny ; Sieh, Weiva ; McGuire, Valerie ; Rothstein, Joseph H. ; Ziogas, Argyrios ; Lubiński, Jan ; Cybulski, Cezary ; Menkiszak, Janusz ; Jensen, Allan ; Gayther, Simon A. ; Ramus, Susan J. ; Gentry-Maharaj, Aleksandra ; Berchuck, Andrew ; Wu, Anna H. ; Pike, Malcolm C. ; Van DenBerg, David ; Terry, Kathryn L. ; Vitonis, Allison F. ; Doherty, Jennifer A. ; Johnatty, Sharon E. ; DeFazio, Anna ; Song, Honglin ; Tyrer, Jonathan ; Sellers, Thomas A. ; Phelan, Catherine M. ; Kalli, Kimberly R. ; Cunningham, Julie M. ; Fridley, Brooke L. ; Goode, Ellen L. / Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 5. pp. 987-992.
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abstract = "Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome,weevaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-92.",
author = "White, {Kristin L.} and Vierkant, {Robert A.} and Fogarty, {Zachary C.} and Bridget Charbonneau and Block, {Matthew S.} and Pharoah, {Paul D P} and Georgia Chenevix-Trench and Rossing, {Mary Anne} and Cramer, {Daniel W.} and Pearce, {Celeste Leigh} and Schildkraut, {Joellen M.} and Usha Menon and Kjaer, {Susanne Kruger} and Levine, {Douglas A.} and Jacek Gronwald and Culver, {Hoda Anton} and Whittemore, {Alice S.} and Karlan, {Beth Y.} and Diether Lambrechts and Nicolas Wentzensen and Jolanta Kupryjanczyk and Jenny Chang-Claude and Bandera, {Elisa V.} and Estrid Hogdall and Florian Heitz and Kaye, {Stanley B.} and Fasching, {Peter A.} and Ian Campbell and Goodman, {Marc T.} and Tanja Pejovic and Yukie Bean and Galina Lurie and Diana Eccles and Alexander Hein and Beckmann, {Matthias W.} and Ekici, {Arif B.} and James Paul and Robert Brown and Flanagan, {James M.} and Philipp Harter and {Du Bois}, Andreas and Ira Schwaab and Hogdall, {Claus K.} and Lene Lundvall and Olson, {Sara H.} and Irene Orlow and Paddock, {Lisa E.} and Anja Rudolph and Ursula Eilber and Agnieszka Dansonka-Mieszkowska and Rzepecka, {Iwona K.} and Izabela Ziolkowska-Seta and Louise Brinton and Hannah Yang and Montserrat Garcia-Closas and Evelyn Despierre and Sandrina Lambrechts and Ignace Vergote and Christine Walsh and Jenny Lester and Weiva Sieh and Valerie McGuire and Rothstein, {Joseph H.} and Argyrios Ziogas and Jan Lubiński and Cezary Cybulski and Janusz Menkiszak and Allan Jensen and Gayther, {Simon A.} and Ramus, {Susan J.} and Aleksandra Gentry-Maharaj and Andrew Berchuck and Wu, {Anna H.} and Pike, {Malcolm C.} and {Van DenBerg}, David and Terry, {Kathryn L.} and Vitonis, {Allison F.} and Doherty, {Jennifer A.} and Johnatty, {Sharon E.} and Anna DeFazio and Honglin Song and Jonathan Tyrer and Sellers, {Thomas A.} and Phelan, {Catherine M.} and Kalli, {Kimberly R.} and Cunningham, {Julie M.} and Fridley, {Brooke L.} and Goode, {Ellen L.}",
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TY - JOUR

T1 - Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

AU - White, Kristin L.

AU - Vierkant, Robert A.

AU - Fogarty, Zachary C.

AU - Charbonneau, Bridget

AU - Block, Matthew S.

AU - Pharoah, Paul D P

AU - Chenevix-Trench, Georgia

AU - Rossing, Mary Anne

AU - Cramer, Daniel W.

AU - Pearce, Celeste Leigh

AU - Schildkraut, Joellen M.

AU - Menon, Usha

AU - Kjaer, Susanne Kruger

AU - Levine, Douglas A.

AU - Gronwald, Jacek

AU - Culver, Hoda Anton

AU - Whittemore, Alice S.

AU - Karlan, Beth Y.

AU - Lambrechts, Diether

AU - Wentzensen, Nicolas

AU - Kupryjanczyk, Jolanta

AU - Chang-Claude, Jenny

AU - Bandera, Elisa V.

AU - Hogdall, Estrid

AU - Heitz, Florian

AU - Kaye, Stanley B.

AU - Fasching, Peter A.

AU - Campbell, Ian

AU - Goodman, Marc T.

AU - Pejovic, Tanja

AU - Bean, Yukie

AU - Lurie, Galina

AU - Eccles, Diana

AU - Hein, Alexander

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Paul, James

AU - Brown, Robert

AU - Flanagan, James M.

AU - Harter, Philipp

AU - Du Bois, Andreas

AU - Schwaab, Ira

AU - Hogdall, Claus K.

AU - Lundvall, Lene

AU - Olson, Sara H.

AU - Orlow, Irene

AU - Paddock, Lisa E.

AU - Rudolph, Anja

AU - Eilber, Ursula

AU - Dansonka-Mieszkowska, Agnieszka

AU - Rzepecka, Iwona K.

AU - Ziolkowska-Seta, Izabela

AU - Brinton, Louise

AU - Yang, Hannah

AU - Garcia-Closas, Montserrat

AU - Despierre, Evelyn

AU - Lambrechts, Sandrina

AU - Vergote, Ignace

AU - Walsh, Christine

AU - Lester, Jenny

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Rothstein, Joseph H.

AU - Ziogas, Argyrios

AU - Lubiński, Jan

AU - Cybulski, Cezary

AU - Menkiszak, Janusz

AU - Jensen, Allan

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Gentry-Maharaj, Aleksandra

AU - Berchuck, Andrew

AU - Wu, Anna H.

AU - Pike, Malcolm C.

AU - Van DenBerg, David

AU - Terry, Kathryn L.

AU - Vitonis, Allison F.

AU - Doherty, Jennifer A.

AU - Johnatty, Sharon E.

AU - DeFazio, Anna

AU - Song, Honglin

AU - Tyrer, Jonathan

AU - Sellers, Thomas A.

AU - Phelan, Catherine M.

AU - Kalli, Kimberly R.

AU - Cunningham, Julie M.

AU - Fridley, Brooke L.

AU - Goode, Ellen L.

PY - 2013/5

Y1 - 2013/5

N2 - Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome,weevaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-92.

AB - Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome,weevaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-92.

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