Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

Joellen M. Schildkraut, Ellen L. Goode, Merlise A. Clyde, Edwin S. Iversen, Patricia G. Moorman, Andrew Berchuck, Jeffrey R. Marks, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Julie M. Cunningham, Robert A. Vierkant, David N. Rider, Georgia Chenevix-Trench, Penelope M. Webb, Jonathan Beesley, Xiaoqing Chen, Catherine Phelan, Rebecca Sutphen, Thomas A. SellersLeigh Pearce, Anna H. Wu, David Den Van Berg, David Conti, Christopher K. Elund, Rebecca Anderson, Marc T. Goodman, Galina Lurie, Michael E. Carney, Pamela J. Thompson, Simon A. Gayther, Susan J. Ramus, Ian Jacobs, Susanne Krüger Kjaer, Estrid Hogdall, Jan Blaakaer, Claus Hogdall, Douglas F. Easton, Honglin Song, Paul D P Pharoah, Alice S. Whittemore, Valerie McGuire, Lydia Quaye, Hoda Anton-Culver, Argyrios Ziogas, Kathryn L. Terry, Daniel W. Cramer, Susan E. Hankinson, Shelley S. Tworoger, Brian Calingaert, Stephen Chanock, Mark Sherman, Montserrat Garcia-Closas

Research output: Contribution to journalArticle

Abstract

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 tps3 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 SMPs 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 (r2 = 0.62) SMPs: rs2287498 (median per allele OB, 1.30; 95% PI, 1.07-1.57) and rsl2951053 (median per allele OR, 1.19; 95% PI, 1.01-1.38). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated with common variants in the TPS3 region.

Original languageEnglish (US)
Pages (from-to)2349-2357
Number of pages9
JournalCancer Research
Volume69
Issue number6
DOIs
StatePublished - Mar 15 2009
Externally publishedYes

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Ovarian Neoplasms
Single Nucleotide Polymorphism
Alleles
Odds Ratio
DNA Repair
Ovarian epithelial cancer
Case-Control Studies
Neoplasms
Logistic Models
Genotype
Growth
Population
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schildkraut, J. M., Goode, E. L., Clyde, M. A., Iversen, E. S., Moorman, P. G., Berchuck, A., ... Garcia-Closas, M. (2009). Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. Cancer Research, 69(6), 2349-2357. https://doi.org/10.1158/0008-5472.CAN-08-2902

Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. / Schildkraut, Joellen M.; Goode, Ellen L.; Clyde, Merlise A.; Iversen, Edwin S.; Moorman, Patricia G.; Berchuck, Andrew; Marks, Jeffrey R.; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Cunningham, Julie M.; Vierkant, Robert A.; Rider, David N.; Chenevix-Trench, Georgia; Webb, Penelope M.; Beesley, Jonathan; Chen, Xiaoqing; Phelan, Catherine; Sutphen, Rebecca; Sellers, Thomas A.; Pearce, Leigh; Wu, Anna H.; Van Berg, David Den; Conti, David; Elund, Christopher K.; Anderson, Rebecca; Goodman, Marc T.; Lurie, Galina; Carney, Michael E.; Thompson, Pamela J.; Gayther, Simon A.; Ramus, Susan J.; Jacobs, Ian; Kjaer, Susanne Krüger; Hogdall, Estrid; Blaakaer, Jan; Hogdall, Claus; Easton, Douglas F.; Song, Honglin; Pharoah, Paul D P; Whittemore, Alice S.; McGuire, Valerie; Quaye, Lydia; Anton-Culver, Hoda; Ziogas, Argyrios; Terry, Kathryn L.; Cramer, Daniel W.; Hankinson, Susan E.; Tworoger, Shelley S.; Calingaert, Brian; Chanock, Stephen; Sherman, Mark; Garcia-Closas, Montserrat.

In: Cancer Research, Vol. 69, No. 6, 15.03.2009, p. 2349-2357.

Research output: Contribution to journalArticle

Schildkraut, JM, Goode, EL, Clyde, MA, Iversen, ES, Moorman, PG, Berchuck, A, Marks, JR, Lissowska, J, Brinton, L, Peplonska, B, Cunningham, JM, Vierkant, RA, Rider, DN, Chenevix-Trench, G, Webb, PM, Beesley, J, Chen, X, Phelan, C, Sutphen, R, Sellers, TA, Pearce, L, Wu, AH, Van Berg, DD, Conti, D, Elund, CK, Anderson, R, Goodman, MT, Lurie, G, Carney, ME, Thompson, PJ, Gayther, SA, Ramus, SJ, Jacobs, I, Kjaer, SK, Hogdall, E, Blaakaer, J, Hogdall, C, Easton, DF, Song, H, Pharoah, PDP, Whittemore, AS, McGuire, V, Quaye, L, Anton-Culver, H, Ziogas, A, Terry, KL, Cramer, DW, Hankinson, SE, Tworoger, SS, Calingaert, B, Chanock, S, Sherman, M & Garcia-Closas, M 2009, 'Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer', Cancer Research, vol. 69, no. 6, pp. 2349-2357. https://doi.org/10.1158/0008-5472.CAN-08-2902
Schildkraut, Joellen M. ; Goode, Ellen L. ; Clyde, Merlise A. ; Iversen, Edwin S. ; Moorman, Patricia G. ; Berchuck, Andrew ; Marks, Jeffrey R. ; Lissowska, Jolanta ; Brinton, Louise ; Peplonska, Beata ; Cunningham, Julie M. ; Vierkant, Robert A. ; Rider, David N. ; Chenevix-Trench, Georgia ; Webb, Penelope M. ; Beesley, Jonathan ; Chen, Xiaoqing ; Phelan, Catherine ; Sutphen, Rebecca ; Sellers, Thomas A. ; Pearce, Leigh ; Wu, Anna H. ; Van Berg, David Den ; Conti, David ; Elund, Christopher K. ; Anderson, Rebecca ; Goodman, Marc T. ; Lurie, Galina ; Carney, Michael E. ; Thompson, Pamela J. ; Gayther, Simon A. ; Ramus, Susan J. ; Jacobs, Ian ; Kjaer, Susanne Krüger ; Hogdall, Estrid ; Blaakaer, Jan ; Hogdall, Claus ; Easton, Douglas F. ; Song, Honglin ; Pharoah, Paul D P ; Whittemore, Alice S. ; McGuire, Valerie ; Quaye, Lydia ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Terry, Kathryn L. ; Cramer, Daniel W. ; Hankinson, Susan E. ; Tworoger, Shelley S. ; Calingaert, Brian ; Chanock, Stephen ; Sherman, Mark ; Garcia-Closas, Montserrat. / Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. In: Cancer Research. 2009 ; Vol. 69, No. 6. pp. 2349-2357.
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AU - Brinton, Louise

AU - Peplonska, Beata

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AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Terry, Kathryn L.

AU - Cramer, Daniel W.

AU - Hankinson, Susan E.

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