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. Sellers; Leigh 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

doi:10.1158/0008-5472.CAN-08-2902

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 journal › Article › peer-review

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. © 2009 American Association for Cancer Research.

Original language	English
Pages (from-to)	2349-2357
Number of pages	8
Journal	Cancer Research
Volume	69
Issue number	6
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-2902
Publication status	Published - 15 Mar 2009

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10.1158/0008-5472.CAN-08-2902

http://cancerres.aacrjournals.org/cgi/reprint/69/6/2349

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Schildkraut, J. M., Goode, E. L., Clyde, M. A., Iversen, E. S., Moorman, P. G., Berchuck, A., Marks, J. R., Lissowska, J., Brinton, L., Peplonska, B., Cunningham, J. M., Vierkant, R. A., Rider, D. N., Chenevix-Trench, G., Webb, P. M., Beesley, J., Chen, X., Phelan, C., Sutphen, R., ... 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

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title = "Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer",

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. {\textcopyright} 2009 American Association for Cancer Research.",

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

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month = mar,

day = "15",

doi = "10.1158/0008-5472.CAN-08-2902",

language = "English",

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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

TY - JOUR

T1 - Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

AU - Schildkraut, Joellen M.

AU - Goode, Ellen L.

AU - Clyde, Merlise A.

AU - Iversen, Edwin S.

AU - Moorman, Patricia G.

AU - Berchuck, Andrew

AU - Marks, Jeffrey R.

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Peplonska, Beata

AU - Cunningham, Julie M.

AU - Vierkant, Robert A.

AU - Rider, David N.

AU - Chenevix-Trench, Georgia

AU - Webb, Penelope M.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Phelan, Catherine

AU - Sutphen, Rebecca

AU - Sellers, Thomas A.

AU - Pearce, Leigh

AU - Wu, Anna H.

AU - Van Berg, David Den

AU - Conti, David

AU - Elund, Christopher K.

AU - Anderson, Rebecca

AU - Goodman, Marc T.

AU - Lurie, Galina

AU - Carney, Michael E.

AU - Thompson, Pamela J.

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Jacobs, Ian

AU - Kjaer, Susanne Krüger

AU - Hogdall, Estrid

AU - Blaakaer, Jan

AU - Hogdall, Claus

AU - Easton, Douglas F.

AU - Song, Honglin

AU - Pharoah, Paul D P

AU - Whittemore, Alice S.

AU - McGuire, Valerie

AU - Quaye, Lydia

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Terry, Kathryn L.

AU - Cramer, Daniel W.

AU - Hankinson, Susan E.

AU - Tworoger, Shelley S.

AU - Calingaert, Brian

AU - Chanock, Stephen

AU - Sherman, Mark

AU - Garcia-Closas, Montserrat

N1 - CA087969, NCI NIH HHS, United StatesCA105009, NCI NIH HHS, United StatesCA122443, NCI NIH HHS, United StatesCA14089, NCI NIH HHS, United StatesCA16056, NCI NIH HHS, United StatesCA17054, NCI NIH HHS, United StatesCA49449, NCI NIH HHS, United StatesCA54419, NCI NIH HHS, United StatesCA58598, NCI NIH HHS, United StatesCA61132, NCI NIH HHS, United StatesCA63464, NCI NIH HHS, United StatesCA71966, NCI NIH HHS, United StatesCA76016, NCI NIH HHS, United StatesHL090559, NHLBI NIH HHS, United StatesN01 PC 35137, NCI NIH HHS, United StatesN01 PC035137, NCI NIH HHS, United StatesN01-67001, PHS HHS, United StatesN01-CN-55424, NCI NIH HHS, United StatesN01-PC-67010, NCI NIH HHS, United StatesNCA76016, PHS HHS, United StatesR01 CA 58598, NCI NIH HHS, United StatesR01 CA058598-10, NCI NIH HHS, United StatesR01 CA076016-10, NCI NIH HHS, United StatesR03-CA113148, NCI NIH HHS, United States

PY - 2009/3/15

Y1 - 2009/3/15

N2 - 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. © 2009 American Association for Cancer Research.

AB - 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. © 2009 American Association for Cancer Research.

U2 - 10.1158/0008-5472.CAN-08-2902

DO - 10.1158/0008-5472.CAN-08-2902

M3 - Article

C2 - 19276375

SN - 1538-7445

VL - 69

SP - 2349

EP - 2357

JO - Cancer Research

JF - Cancer Research

IS - 6

ER -

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

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