Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

Ernest K 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; Laura C Dale; Diether Lambrechts; Frederic Amant; Evelyn Despierre; Ignace Vergote; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Jenny Chang-Claude; Shan Wang-Gohrke; Hoda Anton-Culver; Argyrios Ziogas; Thilo Dörk; Matthias Dürst; Natalia Antonenkova; Natalia Bogdanova; Robert James (Jim) 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; Australian Ovarian Cancer Study Group

doi:http://dx.doi.org/10.1371/journal.pone.0019642

Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

Ernest K 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, Laura C Dale, Diether Lambrechts, Frederic Amant, Evelyn Despierre, Ignace Vergote, Simon A Gayther, Aleksandra Gentry-Maharaj, Usha Menon, Jenny Chang-Claude, Shan Wang-GohrkeHoda Anton-Culver, Argyrios Ziogas, Thilo Dörk, Matthias Dürst, Natalia Antonenkova, Natalia Bogdanova, Robert James (Jim) 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, Australian Ovarian Cancer Study Group

Faculty of Health and Medical Sciences

5 Citations (Scopus)

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 (P(heterogeneity)=0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR¿=¿0.6 to 0.9; P(trend)¿=¿0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)=0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs¿=¿1.2; P(trend)=0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)=0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)=0.003), age at diagnosis (P(interaction)¿=¿0.04), and year of diagnosis (P(interaction)¿=¿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 language	English
Journal	P L o S One
Volume	6
Issue number	5
Pages (from-to)	e19642
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0019642
Publication status	Published - 2011

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Amankwah, E. K., Wang, Q., Schildkraut, J. M., Tsai, Y-Y., Ramus, S. J., Fridley, B. L., Beesley, J., Johnatty, S. E., Webb, P. M., Chenevix-Trench, G., Dale, L. C., Lambrechts, D., Amant, F., Despierre, E., Vergote, I., Gayther, S. A., Gentry-Maharaj, A., Menon, U., Chang-Claude, J., ... Australian Ovarian Cancer Study Group (2011). Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium. P L o S One, 6(5), e19642. https://doi.org/10.1371/journal.pone.0019642

Amankwah, EK, Wang, Q, Schildkraut, JM, Tsai, Y-Y, Ramus, SJ, Fridley, BL, Beesley, J, Johnatty, SE, Webb, PM, Chenevix-Trench, G, 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, RJ, 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 & Australian Ovarian Cancer Study Group 2011, 'Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium', P L o S One, vol. 6, no. 5, pp. e19642. https://doi.org/10.1371/journal.pone.0019642

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title = "Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium",

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 (P(heterogeneity)=0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR¿=¿0.6 to 0.9; P(trend)¿=¿0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)=0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs¿=¿1.2; P(trend)=0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)=0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)=0.003), age at diagnosis (P(interaction)¿=¿0.04), and year of diagnosis (P(interaction)¿=¿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.",

author = "Amankwah, {Ernest K} and Qinggang Wang and Schildkraut, {Joellen M} and Ya-Yu Tsai and Ramus, {Susan J} and Fridley, {Brooke L} and Jonathan Beesley and Johnatty, {Sharon E} and Webb, {Penelope M} and Georgia Chenevix-Trench and Dale, {Laura C} and Diether Lambrechts and Frederic Amant and Evelyn Despierre and Ignace Vergote and Gayther, {Simon A} and Aleksandra Gentry-Maharaj and Usha Menon and Jenny Chang-Claude and Shan Wang-Gohrke and Hoda Anton-Culver and Argyrios Ziogas and Thilo D{\"o}rk and Matthias D{\"u}rst and Natalia Antonenkova and Natalia Bogdanova and Brown, {Robert James (Jim)} and Flanagan, {James M} and Kaye, {Stanley B} and James Paul and Ralf B{\"u}tzow and Heli Nevanlinna and Ian Campbell and Eccles, {Diana M} and Karlan, {Beth Y} and Jenny Gross and Christine Walsh and Pharoah, {Paul D P} and Honglin Song and Susanne Kj{\ae}r and Estrid H{\o}gdall and Claus H{\o}gdall and Lene Lundvall and Lotte Nedergaard and Kiemeney, {Lambertus A L M} and Massuger, {Leon F A G} and {van Altena}, {Anne M} and Vermeulen, {Sita H H M} and Le, {Nhu D} and Angela Brooks-Wilson and H{\o}gdall, {Claus Kim}",

year = "2011",

doi = "http://dx.doi.org/10.1371/journal.pone.0019642",

language = "English",

volume = "6",

pages = "e19642",

journal = "PLoS Computational Biology",

issn = "1932-6203",

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number = "5",

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TY - JOUR

T1 - Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: 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 - 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 James (Jim)

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 - Australian Ovarian Cancer Study Group

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 (P(heterogeneity)=0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR¿=¿0.6 to 0.9; P(trend)¿=¿0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)=0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs¿=¿1.2; P(trend)=0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)=0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)=0.003), age at diagnosis (P(interaction)¿=¿0.04), and year of diagnosis (P(interaction)¿=¿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 (P(heterogeneity)=0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR¿=¿0.6 to 0.9; P(trend)¿=¿0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)=0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs¿=¿1.2; P(trend)=0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)=0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)=0.003), age at diagnosis (P(interaction)¿=¿0.04), and year of diagnosis (P(interaction)¿=¿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.

U2 - http://dx.doi.org/10.1371/journal.pone.0019642

DO - http://dx.doi.org/10.1371/journal.pone.0019642

M3 - Journal article

SN - 1932-6203

VL - 6

SP - e19642

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 5

ER -

Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

Abstract

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