Epithelial ovarian cancer: testing the androgen hypothesis

Olsen, Catherine, Green, A. C, Nagle, C, Susan Jordan, Whiteman, D, Bain, Christopher J. and Webb, P (2008) Epithelial ovarian cancer: testing the androgen hypothesis. Endocrine Related Cancer, 15 4: 1061-1068. doi:10.1677/ERC-08-0075


Author Olsen, Catherine
Green, A. C
Nagle, C
Susan Jordan
Whiteman, D
Bain, Christopher J.
Webb, P
Title Epithelial ovarian cancer: testing the androgen hypothesis
Journal name Endocrine Related Cancer   Check publisher's open access policy
ISSN 1351-0088
1479-6821
Publication date 2008-12-01
Year available 2008
Sub-type Article (original research)
DOI 10.1677/ERC-08-0075
Open Access Status DOI
Volume 15
Issue 4
Start page 1061
End page 1068
Total pages 8
Editor J Fagin
Place of publication The United Kingdom
Publisher Society for Endocrinology
Language eng
Subject C1
920102 Cancer and Related Disorders
111299 Oncology and Carcinogenesis not elsewhere classified
Abstract Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
Keyword Oncology
Endocrinology & Metabolism
Oncology
Endocrinology & Metabolism
ENDOCRINOLOGY & METABOLISM
ONCOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID U01 CA069417
R01 CA050385
N01 PC067010
P50 CA159981
P30 CA016056
R01 CA087538
R01 CA136924
P01 CA087969
R01 CA067262
P30 CA046592
M01 RR000056
P30 CA072720
R01 CA095023
UL1 TR001863
UM1 CA176726
R03 CA113148
R01 CA058598
K22 CA138563
R01 CA058860
R01 CA074850
R01 CA063678
N01PC35137
K07 CA092044
P50 CA105009
K07 CA080668
P30 CA008748
P30 CA014089
R01 CA083918
R03 CA115195
UM1 CA186107
R01 CA054419
R01 CA122443
P30 CA015083
K07 CA143047
R01 CA087696
R01 CA149429
P01 CA017054
N01 CN025403
10119
R01 CA049449
R01 CA063682
K07 CA095666
R01 CA112523
P50 CA136393
R01 CA126841
R01 CA114343
10124
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
2009 Higher Education Research Data Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 34 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 25 Mar 2009, 20:15:49 EST by Geraldine Fitzgerald on behalf of School of Public Health