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Int J Cancer. 2008 Jul 15;123(2):380-388. doi: 10.1002/ijc.23448.

Consortium analysis of 7 candidate SNPs for ovarian cancer.

Author information

1
Translational Research Laboratory, University College London EGA Institute for Women's Health, London, United Kingdom.
2
College of Medicine, Mayo Clinic, Rochester, MN.
3
The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia.
4
University of Southern California, Keck School of Medicine, Los Angeles, CA.
5
Gynaecological Cancer Research Centre, University College London, EGA Institute for Women's Health, London, United Kingdom.
6
Roswell Park Cancer Institute, Buffalo, NY.
7
Stanford University School of Medicine, Stanford, CA.
8
Cancer Research United Kingdom Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
9
Cancer Research United Kingdom Genetic Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
10
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
11
Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
12
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA.
13
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
14
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.
15
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
16
Danish Cancer Society, Copenhagen, Denmark.
17
Rigshospitalet, The Juliane Marie Centre, University of Copenhagen, Copenhagen, Denmark.
18
Aarhus University Hospital, Skejby, Denmark.
19
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
20
Magee-Womens Hospital, Pittsburgh, PA.
21
Cancer Research Center, University of Hawaii, Honolulu, Hawaii.
22
University of Ulm, Ulm, Germany.
23
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.

PMID:
18431743
PMCID:
PMC2667795
DOI:
10.1002/ijc.23448
[Indexed for MEDLINE]
Free PMC Article

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