Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Cancer Research |
Vol/bind | 69 |
Udgave nummer | 6 |
Sider (fra-til) | 2349-57 |
Antal sider | 8 |
ISSN | 0008-5472 |
DOI | |
Status | Udgivet - 2009 |
Bibliografisk 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 AdultAdgang til dokumentet
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I: Cancer Research, Bind 69, Nr. 6, 2009, s. 2349-57.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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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 -