A targeted genetic association study of epithelial ovarian cancer susceptibility

Madalene Earp, Stacey J. Winham, Nicholas Larson, Jennifer B. Permuth, Hugues Sicotte, Jeremy Chien, Hoda Anton-Culver, Elisa V. Bandera, Andrew Berchuck, Linda S. Cook, Daniel Cramer, Jennifer A. Doherty, Marc T. Goodman, Douglas A. Levine, Alvaro N.A. Monteiro, Roberta B. Ness, Celeste L. Pearce, Mary Anne Rossing, Shelley S. Tworoger, Nicolas WentzensenMaria Bisogna, Louise Brinton, Angela Brooks-Wilson, Michael E. Carney, Julie M. Cunningham, Robert P. Edwards, Zachary C. Fogarty, Edwin S. Iversen, Peter Kraft, Melissa C. Larson, Nhu D. Le, Hui Yi Lin, Jolanta Lissowska, Francesmary Modugno, Kirsten B. Moysich, Sara H. Olson, Malcolm C. Pike, Elizabeth M. Poole, David N. Rider, Kathryn L. Terry, Pamela J. Thompson, David Van Den Berg, Robert A. Vierkant, Allison F. Vitonis, Lynne R. Wilkens, Anna H. Wu, Hannah P. Yang, Argyrios Ziogas, Catherine M. Phelan, Joellen M. Schildkraut, Yian Ann Chen, Thomas A. Sellers, Brooke L. Fridley, Ellen L. Goode

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. Results: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10-8), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6). Methods: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. Conclusion: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.

Original languageEnglish (US)
Pages (from-to)7381-7389
Number of pages9
JournalOncotarget
Volume7
Issue number7
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Genetic Association Studies
Genome-Wide Association Study
Ovarian epithelial cancer
Logistic Models
Alleles
Genome
Population

Keywords

  • Genetic association
  • High-grade serous carcinoma
  • NF-κB
  • Ovarian cancer
  • Susceptibility loci

ASJC Scopus subject areas

  • Oncology

Cite this

Earp, M., Winham, S. J., Larson, N., Permuth, J. B., Sicotte, H., Chien, J., ... Goode, E. L. (2016). A targeted genetic association study of epithelial ovarian cancer susceptibility. Oncotarget, 7(7), 7381-7389. https://doi.org/10.18632/oncotarget.7121

A targeted genetic association study of epithelial ovarian cancer susceptibility. / Earp, Madalene; Winham, Stacey J.; Larson, Nicholas; Permuth, Jennifer B.; Sicotte, Hugues; Chien, Jeremy; Anton-Culver, Hoda; Bandera, Elisa V.; Berchuck, Andrew; Cook, Linda S.; Cramer, Daniel; Doherty, Jennifer A.; Goodman, Marc T.; Levine, Douglas A.; Monteiro, Alvaro N.A.; Ness, Roberta B.; Pearce, Celeste L.; Rossing, Mary Anne; Tworoger, Shelley S.; Wentzensen, Nicolas; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E.; Cunningham, Julie M.; Edwards, Robert P.; Fogarty, Zachary C.; Iversen, Edwin S.; Kraft, Peter; Larson, Melissa C.; Le, Nhu D.; Lin, Hui Yi; Lissowska, Jolanta; Modugno, Francesmary; Moysich, Kirsten B.; Olson, Sara H.; Pike, Malcolm C.; Poole, Elizabeth M.; Rider, David N.; Terry, Kathryn L.; Thompson, Pamela J.; Van Den Berg, David; Vierkant, Robert A.; Vitonis, Allison F.; Wilkens, Lynne R.; Wu, Anna H.; Yang, Hannah P.; Ziogas, Argyrios; Phelan, Catherine M.; Schildkraut, Joellen M.; Chen, Yian Ann; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.

In: Oncotarget, Vol. 7, No. 7, 01.01.2016, p. 7381-7389.

Research output: Contribution to journalArticle

Earp, M, Winham, SJ, Larson, N, Permuth, JB, Sicotte, H, Chien, J, Anton-Culver, H, Bandera, EV, Berchuck, A, Cook, LS, Cramer, D, Doherty, JA, Goodman, MT, Levine, DA, Monteiro, ANA, Ness, RB, Pearce, CL, Rossing, MA, Tworoger, SS, Wentzensen, N, Bisogna, M, Brinton, L, Brooks-Wilson, A, Carney, ME, Cunningham, JM, Edwards, RP, Fogarty, ZC, Iversen, ES, Kraft, P, Larson, MC, Le, ND, Lin, HY, Lissowska, J, Modugno, F, Moysich, KB, Olson, SH, Pike, MC, Poole, EM, Rider, DN, Terry, KL, Thompson, PJ, Van Den Berg, D, Vierkant, RA, Vitonis, AF, Wilkens, LR, Wu, AH, Yang, HP, Ziogas, A, Phelan, CM, Schildkraut, JM, Chen, YA, Sellers, TA, Fridley, BL & Goode, EL 2016, 'A targeted genetic association study of epithelial ovarian cancer susceptibility', Oncotarget, vol. 7, no. 7, pp. 7381-7389. https://doi.org/10.18632/oncotarget.7121
Earp, Madalene ; Winham, Stacey J. ; Larson, Nicholas ; Permuth, Jennifer B. ; Sicotte, Hugues ; Chien, Jeremy ; Anton-Culver, Hoda ; Bandera, Elisa V. ; Berchuck, Andrew ; Cook, Linda S. ; Cramer, Daniel ; Doherty, Jennifer A. ; Goodman, Marc T. ; Levine, Douglas A. ; Monteiro, Alvaro N.A. ; Ness, Roberta B. ; Pearce, Celeste L. ; Rossing, Mary Anne ; Tworoger, Shelley S. ; Wentzensen, Nicolas ; Bisogna, Maria ; Brinton, Louise ; Brooks-Wilson, Angela ; Carney, Michael E. ; Cunningham, Julie M. ; Edwards, Robert P. ; Fogarty, Zachary C. ; Iversen, Edwin S. ; Kraft, Peter ; Larson, Melissa C. ; Le, Nhu D. ; Lin, Hui Yi ; Lissowska, Jolanta ; Modugno, Francesmary ; Moysich, Kirsten B. ; Olson, Sara H. ; Pike, Malcolm C. ; Poole, Elizabeth M. ; Rider, David N. ; Terry, Kathryn L. ; Thompson, Pamela J. ; Van Den Berg, David ; Vierkant, Robert A. ; Vitonis, Allison F. ; Wilkens, Lynne R. ; Wu, Anna H. ; Yang, Hannah P. ; Ziogas, Argyrios ; Phelan, Catherine M. ; Schildkraut, Joellen M. ; Chen, Yian Ann ; Sellers, Thomas A. ; Fridley, Brooke L. ; Goode, Ellen L. / A targeted genetic association study of epithelial ovarian cancer susceptibility. In: Oncotarget. 2016 ; Vol. 7, No. 7. pp. 7381-7389.
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abstract = "Background: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. Results: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10-8), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6). Methods: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. Conclusion: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.",
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T1 - A targeted genetic association study of epithelial ovarian cancer susceptibility

AU - Earp, Madalene

AU - Winham, Stacey J.

AU - Larson, Nicholas

AU - Permuth, Jennifer B.

AU - Sicotte, Hugues

AU - Chien, Jeremy

AU - Anton-Culver, Hoda

AU - Bandera, Elisa V.

AU - Berchuck, Andrew

AU - Cook, Linda S.

AU - Cramer, Daniel

AU - Doherty, Jennifer A.

AU - Goodman, Marc T.

AU - Levine, Douglas A.

AU - Monteiro, Alvaro N.A.

AU - Ness, Roberta B.

AU - Pearce, Celeste L.

AU - Rossing, Mary Anne

AU - Tworoger, Shelley S.

AU - Wentzensen, Nicolas

AU - Bisogna, Maria

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Carney, Michael E.

AU - Cunningham, Julie M.

AU - Edwards, Robert P.

AU - Fogarty, Zachary C.

AU - Iversen, Edwin S.

AU - Kraft, Peter

AU - Larson, Melissa C.

AU - Le, Nhu D.

AU - Lin, Hui Yi

AU - Lissowska, Jolanta

AU - Modugno, Francesmary

AU - Moysich, Kirsten B.

AU - Olson, Sara H.

AU - Pike, Malcolm C.

AU - Poole, Elizabeth M.

AU - Rider, David N.

AU - Terry, Kathryn L.

AU - Thompson, Pamela J.

AU - Van Den Berg, David

AU - Vierkant, Robert A.

AU - Vitonis, Allison F.

AU - Wilkens, Lynne R.

AU - Wu, Anna H.

AU - Yang, Hannah P.

AU - Ziogas, Argyrios

AU - Phelan, Catherine M.

AU - Schildkraut, Joellen M.

AU - Chen, Yian Ann

AU - Sellers, Thomas A.

AU - Fridley, Brooke L.

AU - Goode, Ellen L.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. Results: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10-8), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6). Methods: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. Conclusion: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.

AB - Background: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. Results: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10-8), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6). Methods: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. Conclusion: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.

KW - Genetic association

KW - High-grade serous carcinoma

KW - NF-κB

KW - Ovarian cancer

KW - Susceptibility loci

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