Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

Maria Notaridou; Lydia Quaye; Dimitra Dafou; Chris Jones; Honglin Song; Estrid Høgdall; Susanne K Kjaer; Lise Hanne Christensen; Claus Høgdall; Jan Blaakaer; Valerie McGuire; Anna H Wu; David J Van Den Berg; Malcolm C Pike; Aleksandra Gentry-Maharaj; Eva Wozniak; Tanya Sher; Ian J Jacobs; Jonathan Tyrer; Joellen M Schildkraut; Patricia G Moorman; Edwin S Iversen; Anna Jakubowska; Krzysztof Medrek; Jan Lubinski; Roberta B Ness; Kirsten B Moysich; Galina Lurie; Lynne R Wilkens; Michael E Carney; Shan Wang-Gohrke; Jennifer A Doherty; Mary Anne Rossing; Matthias W Beckmann; Falk C Thiel; Arif B Ekici; Xiaoqing Chen; Jonathan Beesley; Jacek Gronwald; Peter A Fasching; Jenny Chang-Claude; Marc T Goodman; Georgia Chenevix-Trench; Andrew Berchuck; C Leigh Pearce; Alice S Whittemore; Usha Menon; Paul D P Pharoah; Simon A Gayther; Susan J Ramus; Australian Ovarian Cancer Study Group/Australian Cancer Study (Ovarian Cancer)

doi:10.1002/ijc.25554

Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

Maria Notaridou, Lydia Quaye, Dimitra Dafou, Chris Jones, Honglin Song, Estrid Høgdall, Susanne K Kjaer, Lise Hanne Christensen, Claus Høgdall, Jan Blaakaer, Valerie McGuire, Anna H Wu, David J Van Den Berg, Malcolm C Pike, Aleksandra Gentry-Maharaj, Eva Wozniak, Tanya Sher, Ian J Jacobs, Jonathan Tyrer, Joellen M SchildkrautPatricia G Moorman, Edwin S Iversen, Anna Jakubowska, Krzysztof Medrek, Jan Lubinski, Roberta B Ness, Kirsten B Moysich, Galina Lurie, Lynne R Wilkens, Michael E Carney, Shan Wang-Gohrke, Jennifer A Doherty, Mary Anne Rossing, Matthias W Beckmann, Falk C Thiel, Arif B Ekici, Xiaoqing Chen, Jonathan Beesley, Jacek Gronwald, Peter A Fasching, Jenny Chang-Claude, Marc T Goodman, Georgia Chenevix-Trench, Andrew Berchuck, C Leigh Pearce, Alice S Whittemore, Usha Menon, Paul D P Pharoah, Simon A Gayther, Susan J Ramus, Australian Ovarian Cancer Study Group/Australian Cancer Study (Ovarian Cancer)

Faculty of Health and Medical Sciences

46 Citations (Scopus)

Abstract

Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcellmediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15-1.74) and the HomOR = 1.63 (1.10-1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80-1.17), HomOR = 0.74 (0.58-0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.

Original language	English
Journal	International Journal of Cancer
Volume	128
Issue number	9
Pages (from-to)	2063-74
Number of pages	12
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.25554 https://doi.org/10.1002/ijc.25554
Publication status	Published - 1 May 2011

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Notaridou, M., Quaye, L., Dafou, D., Jones, C., Song, H., Høgdall, E., Kjaer, S. K., Christensen, L. H., Høgdall, C., Blaakaer, J., McGuire, V., Wu, A. H., Van Den Berg, D. J., Pike, M. C., Gentry-Maharaj, A., Wozniak, E., Sher, T., Jacobs, I. J., Tyrer, J., ... Australian Ovarian Cancer Study Group/Australian Cancer Study (Ovarian Cancer) (2011). Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer. International Journal of Cancer, 128(9), 2063-74. https://doi.org/10.1002/ijc.25554, https://doi.org/10.1002/ijc.25554

Notaridou, M, Quaye, L, Dafou, D, Jones, C, Song, H, Høgdall, E, Kjaer, SK, Christensen, LH, Høgdall, C, Blaakaer, J, McGuire, V, Wu, AH, Van Den Berg, DJ, Pike, MC, Gentry-Maharaj, A, Wozniak, E, Sher, T, Jacobs, IJ, Tyrer, J, Schildkraut, JM, Moorman, PG, Iversen, ES, Jakubowska, A, Medrek, K, Lubinski, J, Ness, RB, Moysich, KB, Lurie, G, Wilkens, LR, Carney, ME, Wang-Gohrke, S, Doherty, JA, Rossing, MA, Beckmann, MW, Thiel, FC, Ekici, AB, Chen, X, Beesley, J, Gronwald, J, Fasching, PA, Chang-Claude, J, Goodman, MT, Chenevix-Trench, G, Berchuck, A, Pearce, CL, Whittemore, AS, Menon, U, Pharoah, PDP, Gayther, SA, Ramus, SJ & Australian Ovarian Cancer Study Group/Australian Cancer Study (Ovarian Cancer) 2011, 'Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer', International Journal of Cancer, vol. 128, no. 9, pp. 2063-74. https://doi.org/10.1002/ijc.25554, https://doi.org/10.1002/ijc.25554

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title = "Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer",

abstract = "Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcellmediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15-1.74) and the HomOR = 1.63 (1.10-1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80-1.17), HomOR = 0.74 (0.58-0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.",

author = "Maria Notaridou and Lydia Quaye and Dimitra Dafou and Chris Jones and Honglin Song and Estrid H{\o}gdall and Kjaer, {Susanne K} and Christensen, {Lise Hanne} and Claus H{\o}gdall and Jan Blaakaer and Valerie McGuire and Wu, {Anna H} and {Van Den Berg}, {David J} and Pike, {Malcolm C} and Aleksandra Gentry-Maharaj and Eva Wozniak and Tanya Sher and Jacobs, {Ian J} and Jonathan Tyrer and Schildkraut, {Joellen M} and Moorman, {Patricia G} and Iversen, {Edwin S} and Anna Jakubowska and Krzysztof Medrek and Jan Lubinski and Ness, {Roberta B} and Moysich, {Kirsten B} and Galina Lurie and Wilkens, {Lynne R} and Carney, {Michael E} and Shan Wang-Gohrke and Doherty, {Jennifer A} and Rossing, {Mary Anne} and Beckmann, {Matthias W} and Thiel, {Falk C} and Ekici, {Arif B} and Xiaoqing Chen and Jonathan Beesley and Jacek Gronwald and Fasching, {Peter A} and Jenny Chang-Claude and Goodman, {Marc T} and Georgia Chenevix-Trench and Andrew Berchuck and Pearce, {C Leigh} and Whittemore, {Alice S} and Usha Menon and Pharoah, {Paul D P} and Gayther, {Simon A} and Ramus, {Susan J} and H{\o}gdall, {Claus Kim}",

note = "Copyright {\textcopyright} 2010 UICC.",

year = "2011",

month = may,

day = "1",

doi = "10.1002/ijc.25554",

language = "English",

volume = "128",

pages = "2063--74",

journal = "Radiation Oncology Investigations",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "9",

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TY - JOUR

T1 - Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

AU - Notaridou, Maria

AU - Quaye, Lydia

AU - Dafou, Dimitra

AU - Jones, Chris

AU - Song, Honglin

AU - Høgdall, Estrid

AU - Kjaer, Susanne K

AU - Christensen, Lise Hanne

AU - Høgdall, Claus

AU - Blaakaer, Jan

AU - McGuire, Valerie

AU - Wu, Anna H

AU - Van Den Berg, David J

AU - Pike, Malcolm C

AU - Gentry-Maharaj, Aleksandra

AU - Wozniak, Eva

AU - Sher, Tanya

AU - Jacobs, Ian J

AU - Tyrer, Jonathan

AU - Schildkraut, Joellen M

AU - Moorman, Patricia G

AU - Iversen, Edwin S

AU - Jakubowska, Anna

AU - Medrek, Krzysztof

AU - Lubinski, Jan

AU - Ness, Roberta B

AU - Moysich, Kirsten B

AU - Lurie, Galina

AU - Wilkens, Lynne R

AU - Carney, Michael E

AU - Wang-Gohrke, Shan

AU - Doherty, Jennifer A

AU - Rossing, Mary Anne

AU - Beckmann, Matthias W

AU - Thiel, Falk C

AU - Ekici, Arif B

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Gronwald, Jacek

AU - Fasching, Peter A

AU - Chang-Claude, Jenny

AU - Goodman, Marc T

AU - Chenevix-Trench, Georgia

AU - Berchuck, Andrew

AU - Pearce, C Leigh

AU - Whittemore, Alice S

AU - Menon, Usha

AU - Pharoah, Paul D P

AU - Gayther, Simon A

AU - Ramus, Susan J

AU - Australian Ovarian Cancer Study Group/Australian Cancer Study (Ovarian Cancer)

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcellmediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15-1.74) and the HomOR = 1.63 (1.10-1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80-1.17), HomOR = 0.74 (0.58-0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.

AB - Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcellmediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15-1.74) and the HomOR = 1.63 (1.10-1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80-1.17), HomOR = 0.74 (0.58-0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.

U2 - 10.1002/ijc.25554

DO - 10.1002/ijc.25554

M3 - Journal article

C2 - 20635389

SN - 0020-7136

VL - 128

SP - 2063

EP - 2074

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

IS - 9

ER -

Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

Abstract

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