Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer

A report from the ovarian cancer association consortium

Ernest Amankwah, Qinggang Wang, Joellen M. Schildkraut, Ya Yu Tsai, Susan J. Ramus, Brooke L. Fridley, Jonathan Beesley, Sharon E. Johnatty, Penelope M. Webb, Georgia Chenevix-Trench, Ovarian Cancer Study Group Australian Ovarian Cancer Study Group, Laura C. Dale, Diether Lambrechts, Frederic Amant, Evelyn Despierre, Ignace Vergote, Simon A. Gayther, Aleksandra Gentry-Maharaj, Usha Menon, Jenny Chang-Claude & 41 others Shan Wang-Gohrke, Hoda Anton-Culver, Argyrios Ziogas, Thilo Dörk, Matthias Dürst, Natalia Antonenkova, Natalia Bogdanova, Robert Brown, James M. Flanagan, Stanley B. Kaye, James Paul, Ralf Bützow, Heli Nevanlinna, Ian Campbell, Diana M. Eccles, Beth Y. Karlan, Jenny Gross, Christine Walsh, Paul D P Pharoah, Honglin Song, Susanne Kjær, Estrid Høgdall, Claus Høgdall, Lene Lundvall, Lotte Nedergaard, Lambertus A L M Kiemeney, Leon F A G Massuger, Anne M. van Altena, Sita H H M Vermeulen, Nhu D. Le, Angela Brooks-Wilson, Linda S. Cook, Catherine M. Phelan, Julie M. Cunningham, Celine M. Vachon, Robert A. Vierkant, Edwin S. Iversen, Andrew Berchuck, Ellen L. Goode, Thomas A. Sellers, Linda E. Kelemen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere19642
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Decorin
ovarian neoplasms
Polymorphism
polymorphism
Ovarian Neoplasms
Genes
odds ratio
genes
Odds Ratio
risk reduction
carcinogenesis
Carcinogenesis
Lumican
Ovarian epithelial cancer
Tissue

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer : A report from the ovarian cancer association consortium. / Amankwah, Ernest; Wang, Qinggang; Schildkraut, Joellen M.; Tsai, Ya Yu; Ramus, Susan J.; Fridley, Brooke L.; Beesley, Jonathan; Johnatty, Sharon E.; Webb, Penelope M.; Chenevix-Trench, Georgia; Australian Ovarian Cancer Study Group, Ovarian Cancer Study Group; Dale, Laura C.; Lambrechts, Diether; Amant, Frederic; Despierre, Evelyn; Vergote, Ignace; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Chang-Claude, Jenny; Wang-Gohrke, Shan; Anton-Culver, Hoda; Ziogas, Argyrios; Dörk, Thilo; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Brown, Robert; Flanagan, James M.; Kaye, Stanley B.; Paul, James; Bützow, Ralf; Nevanlinna, Heli; Campbell, Ian; Eccles, Diana M.; Karlan, Beth Y.; Gross, Jenny; Walsh, Christine; Pharoah, Paul D P; Song, Honglin; Kjær, Susanne; Høgdall, Estrid; Høgdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Kiemeney, Lambertus A L M; Massuger, Leon F A G; van Altena, Anne M.; Vermeulen, Sita H H M; Le, Nhu D.; Brooks-Wilson, Angela; Cook, Linda S.; Phelan, Catherine M.; Cunningham, Julie M.; Vachon, Celine M.; Vierkant, Robert A.; Iversen, Edwin S.; Berchuck, Andrew; Goode, Ellen L.; Sellers, Thomas A.; Kelemen, Linda E.

In: PLoS One, Vol. 6, No. 5, e19642, 2011.

Research output: Contribution to journalArticle

Amankwah, E, Wang, Q, Schildkraut, JM, Tsai, YY, Ramus, SJ, Fridley, BL, Beesley, J, Johnatty, SE, Webb, PM, Chenevix-Trench, G, Australian Ovarian Cancer Study Group, OCSG, Dale, LC, Lambrechts, D, Amant, F, Despierre, E, Vergote, I, Gayther, SA, Gentry-Maharaj, A, Menon, U, Chang-Claude, J, Wang-Gohrke, S, Anton-Culver, H, Ziogas, A, Dörk, T, Dürst, M, Antonenkova, N, Bogdanova, N, Brown, R, Flanagan, JM, Kaye, SB, Paul, J, Bützow, R, Nevanlinna, H, Campbell, I, Eccles, DM, Karlan, BY, Gross, J, Walsh, C, Pharoah, PDP, Song, H, Kjær, S, Høgdall, E, Høgdall, C, Lundvall, L, Nedergaard, L, Kiemeney, LALM, Massuger, LFAG, van Altena, AM, Vermeulen, SHHM, Le, ND, Brooks-Wilson, A, Cook, LS, Phelan, CM, Cunningham, JM, Vachon, CM, Vierkant, RA, Iversen, ES, Berchuck, A, Goode, EL, Sellers, TA & Kelemen, LE 2011, 'Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: A report from the ovarian cancer association consortium', PLoS One, vol. 6, no. 5, e19642. https://doi.org/10.1371/journal.pone.0019642
Amankwah, Ernest ; Wang, Qinggang ; Schildkraut, Joellen M. ; Tsai, Ya Yu ; Ramus, Susan J. ; Fridley, Brooke L. ; Beesley, Jonathan ; Johnatty, Sharon E. ; Webb, Penelope M. ; Chenevix-Trench, Georgia ; Australian Ovarian Cancer Study Group, Ovarian Cancer Study Group ; Dale, Laura C. ; Lambrechts, Diether ; Amant, Frederic ; Despierre, Evelyn ; Vergote, Ignace ; Gayther, Simon A. ; Gentry-Maharaj, Aleksandra ; Menon, Usha ; Chang-Claude, Jenny ; Wang-Gohrke, Shan ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Dörk, Thilo ; Dürst, Matthias ; Antonenkova, Natalia ; Bogdanova, Natalia ; Brown, Robert ; Flanagan, James M. ; Kaye, Stanley B. ; Paul, James ; Bützow, Ralf ; Nevanlinna, Heli ; Campbell, Ian ; Eccles, Diana M. ; Karlan, Beth Y. ; Gross, Jenny ; Walsh, Christine ; Pharoah, Paul D P ; Song, Honglin ; Kjær, Susanne ; Høgdall, Estrid ; Høgdall, Claus ; Lundvall, Lene ; Nedergaard, Lotte ; Kiemeney, Lambertus A L M ; Massuger, Leon F A G ; van Altena, Anne M. ; Vermeulen, Sita H H M ; Le, Nhu D. ; Brooks-Wilson, Angela ; Cook, Linda S. ; Phelan, Catherine M. ; Cunningham, Julie M. ; Vachon, Celine M. ; Vierkant, Robert A. ; Iversen, Edwin S. ; Berchuck, Andrew ; Goode, Ellen L. ; Sellers, Thomas A. ; Kelemen, Linda E. / Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer : A report from the ovarian cancer association consortium. In: PLoS One. 2011 ; Vol. 6, No. 5.
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abstract = "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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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

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.

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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