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 Van Den 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; Australian Ovarian Cancer Study Group

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 Van Den 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, Australian Ovarian Cancer Study Group

54 Citations (Scopus)

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 TP53 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 SNPs 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 (r(2) = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI, 1.07-1.57) and rs12951053 (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 TP53 region.

Original language	English
Journal	Cancer Research
Volume	69
Issue number	6
Pages (from-to)	2349-57
Number of pages	8
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-2902
Publication status	Published - 2009

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10.1158/0008-5472.CAN-08-2902

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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., ... Australian Ovarian Cancer Study Group (2009). Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. Cancer Research, 69(6), 2349-57. https://doi.org/10.1158/0008-5472.CAN-08-2902

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 Den Berg, D, Conti, D, Elund, CK, Anderson, R, Goodman, MT, Lurie, G, Carney, ME, Thompson, PJ, Gayther, SA, Ramus, SJ, Jacobs, I, Krüger Kjaer, S, 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 & Australian Ovarian Cancer Study Group 2009, 'Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer', Cancer Research, vol. 69, no. 6, pp. 2349-57. https://doi.org/10.1158/0008-5472.CAN-08-2902

@article{a0a4a470689311df928f000ea68e967b,

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 TP53 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 SNPs 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 (r(2) = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI, 1.07-1.57) and rs12951053 (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 TP53 region.",

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 Den Berg}, David 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 {Kr{\"u}ger Kjaer}, Susanne 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 {Australian Ovarian Cancer Study Group}",

note = "Keywords: Adult; Aged; Alleles; Female; Genes, p53; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Young Adult",

year = "2009",

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

language = "English",

volume = "69",

pages = "2349--57",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research",

number = "6",

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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 Den Berg, David

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 - Krüger Kjaer, Susanne

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 - Australian Ovarian Cancer Study Group

N1 - Keywords: Adult; Aged; Alleles; Female; Genes, p53; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Young Adult

PY - 2009

Y1 - 2009

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 TP53 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 SNPs 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 (r(2) = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI, 1.07-1.57) and rs12951053 (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 TP53 region.

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 TP53 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 SNPs 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 (r(2) = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI, 1.07-1.57) and rs12951053 (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 TP53 region.

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

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

M3 - Journal article

C2 - 19276375

SN - 0008-5472

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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