TY - JOUR
T1 - Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer
T2 - A report from the ovarian cancer association consortium
AU - Amankwah, Ernest K.
AU - Wang, Qinggang
AU - Schildkraut, Joellen M.
AU - Tsai, Ya Yu
AU - Ramus, Susan J.
AU - Fridley, Brooke L.
AU - Beesley, Jonathan
AU - Johnatty, Sharon E.
AU - Webb, Penelope M.
AU - Chenevix-Trench, Georgia
AU - Australian Ovarian Cancer Study Group, Ovarian Cancer Study Group
AU - Dale, Laura C.
AU - Lambrechts, Diether
AU - Amant, Frederic
AU - Despierre, Evelyn
AU - Vergote, Ignace
AU - Gayther, Simon A.
AU - Gentry-Maharaj, Aleksandra
AU - Menon, Usha
AU - Chang-Claude, Jenny
AU - Wang-Gohrke, Shan
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Dörk, Thilo
AU - Dürst, Matthias
AU - Antonenkova, Natalia
AU - Bogdanova, Natalia
AU - Brown, Robert
AU - Flanagan, James M.
AU - Kaye, Stanley B.
AU - Paul, James
AU - Bützow, Ralf
AU - Nevanlinna, Heli
AU - Campbell, Ian
AU - Eccles, Diana M.
AU - Karlan, Beth Y.
AU - Gross, Jenny
AU - Walsh, Christine
AU - Pharoah, Paul D.P.
AU - Song, Honglin
AU - Kjær, Susanne
AU - Høgdall, Estrid
AU - Høgdall, Claus
AU - Lundvall, Lene
AU - Nedergaard, Lotte
AU - Kiemeney, Lambertus A.L.M.
AU - Massuger, Leon F.A.G.
AU - van Altena, Anne M.
AU - Vermeulen, Sita H.H.M.
AU - Le, Nhu D.
AU - Brooks-Wilson, Angela
AU - Cook, Linda S.
AU - Phelan, Catherine M.
AU - Cunningham, Julie M.
AU - Vachon, Celine M.
AU - Vierkant, Robert A.
AU - Iversen, Edwin S.
AU - Berchuck, Andrew
AU - Goode, Ellen L.
AU - Sellers, Thomas A.
AU - Kelemen, Linda E.
N1 - Funding Information:
We thank Amber Burt for assistance with OCAC data management and Dr Harvey Risch for insightful comments on the hormonal etiology of ovarian cancer. The AOCS Management Group (D Bowtell, G Chenevix-Trench, A deFazio, D Gertig, A Green, and P Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www.aocstudy.org/ ). The AOCS and ACS Management Group (A Green, P Parsons, N Hayward, P Webb, and D Whiteman) thank all of the project staff, collaborating institutions and study participants. The HAN-HJO study gratefully acknowledges the contribution of Drs Frauke Kramer and Wen Zheng to the recruitment of patients at Hannover Medical School. The HAN-HMO study gratefully acknowledges the help of Lena Gacucova in sample preparation. The OVA study gratefully acknowledges Barbara Jamieson, Donna Kan and Rozmin Janoo-Gilani for their assistance with data management and sample preparation. The SEA investigators thank the SEARCH team and the Eastern Cancer Registration and Information Centre for patient recruitment. SRO gratefully acknowledges support from Scottish Gynaecological Clinical Trials Group investigators. The UKO investigators thank Ian Jacobs, Eva Wozniak, Andy Ryan, Jeremy Ford, Nayala Balogun and Martin Widschwendter for their contribution to the study, and Clarissa Ganda, Eva Wozniak and Chris Jones who preformed the replication set 2 genotyping and bioinformatics.
PY - 2011
Y1 - 2011
N2 - Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.
AB - Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.
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U2 - 10.1371/journal.pone.0019642
DO - 10.1371/journal.pone.0019642
M3 - Article
C2 - 21637745
AN - SCOPUS:79957596056
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 5
M1 - e19642
ER -