Consortium analysis of 7 candidate SNPs for ovarian cancer

Susan J. Ramus, Robert A. Vierkant, Sharon E. Johnatty, Malcolm C. Pike, David J. Van Den Berg, Anna H. Wu, Celeste Leigh Pearce, Usha Menon, Aleksandra Gentry-Maharaj, Simon A. Gayther, Richard A. DiCioccio, Valerie McGuire, Alice S. Whittemore, Honglin Song, Douglas F. Easton, Paul D P Pharoah, Montserrat Garcia-Closas, Stephen Chanock, Jolanta Lissowska, Louise Brinton & 150 others Kathryn L. Terry, Daniel W. Cramer, Shelley S. Tworoger, Susan E. Hankinson, Andrew Berchuck, Patricia G. Moorman, Joellen M. Schildkraut, Julie M. Cunningham, Mark Liebow, Susanne Krüger Kjaer, Estrid Hogdall, Claus Hogdall, Jan Blaakaer, Roberta B. Ness, Kirsten B. Moysich, Robert P. Edwards, Michael E. Carney, Galina Lurie, Marc T. Goodman, Shan Wang-Gohrke, Silke Kropp, Jenny Chang-Claude, Penelope M. Webb, Xiaoqing Chen, Jonathan Beesley, Georgia Chenevix-Trench, Ellen L. Goode, D. Bowtell, G. Chenevix-Trench, A. Green, P. Webb, A. DeFazio, D. Gertig, N. Traficante, S. Moore, J. Hung, S. Fereday, K. Harrap, T. Sadkowsky, A. Mellon, R. Robertson, T. Vanden Bergh, J. Maidens, K. Nattress, Y. E. Chiew, A. Stenlake, H. Sullivan, B. Alexander, P. Ashover, S. Brown, T. Corrish, L. Green, L. Jackman, K. Martin, B. Ranieri, J. White, V. Jayde, V. L. Bowes, P. Mamers, T. Schmidt, H. Shirley, S. Viduka, H. Tran, S. Bilic, L. Glavinas, A. Proietto, S. Braye, G. Otton, T. Bonaventura, J. Stewart, M. Friedlander, D. Bell, S. Baron-Hay, A. Ferrier, G. Gard, D. Nevell, B. Young, C. Camaris, R. Crouch, L. Edwards, N. Hacker, D. Marsden, G. Robertson, P. Beale, J. Beith, J. Carter, C. Dalrymple, A. Hamilton, R. Houghton, P. Russell, A. Brand, R. Jaworski, P. Harnett, G. Wain, A. Crandon, M. Cummings, K. Horwood, A. Obermair, D. Wyld, J. Nicklin, D. Papadimos, L. Perrin, B. Ward, M. Davy, C. Hall, T. Dodd, T. Healy, K. Pittman, D. Henderson, S. Hyde, J. Miller, J. Pierdes, P. Blomfield, D. Challis, R. McIntosh, A. Parker, B. Brown, R. Rome, D. Allen, P. Grant, R. Laurie, M. Robbie, D. Healy, T. Jobling, T. Maniolitas, J. McNealage, P. Rogers, B. Susil, A. Veitch, J. Constable, S. Ping Tong, I. Robinson, I. Simpson, K. Phillips, D. Rischin, P. Waring, M. Loughrey, N. O'Callaghan, Bill Murray, V. Billson, S. Galloway, J. Pyman, M. Quinn, I. Hammond, A. McCartney, Y. Leung, I. Haviv, D. Purdie, D. Whiteman, N. Zeps

Research output: Contribution to journalArticle

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.

Original languageEnglish (US)
Pages (from-to)380-388
Number of pages9
JournalInternational Journal of Cancer
Volume123
Issue number2
DOIs
StatePublished - Jul 15 2008
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Aurora Kinase A
Breast Neoplasms
3' Untranslated Regions
Sample Size
Introns

Keywords

  • Association study
  • Neoplasms
  • Ovarian cancer
  • Replication
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Ramus, S. J., Vierkant, R. A., Johnatty, S. E., Pike, M. C., Van Den Berg, D. J., Wu, A. H., ... Zeps, N. (2008). Consortium analysis of 7 candidate SNPs for ovarian cancer. International Journal of Cancer, 123(2), 380-388. https://doi.org/10.1002/ijc.23448

Consortium analysis of 7 candidate SNPs for ovarian cancer. / Ramus, Susan J.; Vierkant, Robert A.; Johnatty, Sharon E.; Pike, Malcolm C.; Van Den Berg, David J.; Wu, Anna H.; Pearce, Celeste Leigh; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; DiCioccio, Richard A.; McGuire, Valerie; Whittemore, Alice S.; Song, Honglin; Easton, Douglas F.; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Brinton, Louise; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Hankinson, Susan E.; Berchuck, Andrew; Moorman, Patricia G.; Schildkraut, Joellen M.; Cunningham, Julie M.; Liebow, Mark; Kjaer, Susanne Krüger; Hogdall, Estrid; Hogdall, Claus; Blaakaer, Jan; Ness, Roberta B.; Moysich, Kirsten B.; Edwards, Robert P.; Carney, Michael E.; Lurie, Galina; Goodman, Marc T.; Wang-Gohrke, Shan; Kropp, Silke; Chang-Claude, Jenny; Webb, Penelope M.; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia; Goode, Ellen L.; Bowtell, D.; Chenevix-Trench, G.; Green, A.; Webb, P.; DeFazio, A.; Gertig, D.; Traficante, N.; Moore, S.; Hung, J.; Fereday, S.; Harrap, K.; Sadkowsky, T.; Mellon, A.; Robertson, R.; Vanden Bergh, T.; Maidens, J.; Nattress, K.; Chiew, Y. E.; Stenlake, A.; Sullivan, H.; Alexander, B.; Ashover, P.; Brown, S.; Corrish, T.; Green, L.; Jackman, L.; Martin, K.; Ranieri, B.; White, J.; Jayde, V.; Bowes, V. L.; Mamers, P.; Schmidt, T.; Shirley, H.; Viduka, S.; Tran, H.; Bilic, S.; Glavinas, L.; Proietto, A.; Braye, S.; Otton, G.; Bonaventura, T.; Stewart, J.; Friedlander, M.; Bell, D.; Baron-Hay, S.; Ferrier, A.; Gard, G.; Nevell, D.; Young, B.; Camaris, C.; Crouch, R.; Edwards, L.; Hacker, N.; Marsden, D.; Robertson, G.; Beale, P.; Beith, J.; Carter, J.; Dalrymple, C.; Hamilton, A.; Houghton, R.; Russell, P.; Brand, A.; Jaworski, R.; Harnett, P.; Wain, G.; Crandon, A.; Cummings, M.; Horwood, K.; Obermair, A.; Wyld, D.; Nicklin, J.; Papadimos, D.; Perrin, L.; Ward, B.; Davy, M.; Hall, C.; Dodd, T.; Healy, T.; Pittman, K.; Henderson, D.; Hyde, S.; Miller, J.; Pierdes, J.; Blomfield, P.; Challis, D.; McIntosh, R.; Parker, A.; Brown, B.; Rome, R.; Allen, D.; Grant, P.; Laurie, R.; Robbie, M.; Healy, D.; Jobling, T.; Maniolitas, T.; McNealage, J.; Rogers, P.; Susil, B.; Veitch, A.; Constable, J.; Ping Tong, S.; Robinson, I.; Simpson, I.; Phillips, K.; Rischin, D.; Waring, P.; Loughrey, M.; O'Callaghan, N.; Murray, Bill; Billson, V.; Galloway, S.; Pyman, J.; Quinn, M.; Hammond, I.; McCartney, A.; Leung, Y.; Haviv, I.; Purdie, D.; Whiteman, D.; Zeps, N.

In: International Journal of Cancer, Vol. 123, No. 2, 15.07.2008, p. 380-388.

Research output: Contribution to journalArticle

Ramus, SJ, Vierkant, RA, Johnatty, SE, Pike, MC, Van Den Berg, DJ, Wu, AH, Pearce, CL, Menon, U, Gentry-Maharaj, A, Gayther, SA, DiCioccio, RA, McGuire, V, Whittemore, AS, Song, H, Easton, DF, Pharoah, PDP, Garcia-Closas, M, Chanock, S, Lissowska, J, Brinton, L, Terry, KL, Cramer, DW, Tworoger, SS, Hankinson, SE, Berchuck, A, Moorman, PG, Schildkraut, JM, Cunningham, JM, Liebow, M, Kjaer, SK, Hogdall, E, Hogdall, C, Blaakaer, J, Ness, RB, Moysich, KB, Edwards, RP, Carney, ME, Lurie, G, Goodman, MT, Wang-Gohrke, S, Kropp, S, Chang-Claude, J, Webb, PM, Chen, X, Beesley, J, Chenevix-Trench, G, Goode, EL, Bowtell, D, Chenevix-Trench, G, Green, A, Webb, P, DeFazio, A, Gertig, D, Traficante, N, Moore, S, Hung, J, Fereday, S, Harrap, K, Sadkowsky, T, Mellon, A, Robertson, R, Vanden Bergh, T, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Martin, K, Ranieri, B, White, J, Jayde, V, Bowes, VL, Mamers, P, Schmidt, T, Shirley, H, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Proietto, A, Braye, S, Otton, G, Bonaventura, T, Stewart, J, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Hamilton, A, Houghton, R, Russell, P, Brand, A, Jaworski, R, Harnett, P, Wain, G, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Wyld, D, Nicklin, J, Papadimos, D, Perrin, L, Ward, B, Davy, M, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Hyde, S, Miller, J, Pierdes, J, Blomfield, P, Challis, D, McIntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Laurie, R, Robbie, M, Healy, D, Jobling, T, Maniolitas, T, McNealage, J, Rogers, P, Susil, B, Veitch, A, Constable, J, Ping Tong, S, Robinson, I, Simpson, I, Phillips, K, Rischin, D, Waring, P, Loughrey, M, O'Callaghan, N, Murray, B, Billson, V, Galloway, S, Pyman, J, Quinn, M, Hammond, I, McCartney, A, Leung, Y, Haviv, I, Purdie, D, Whiteman, D & Zeps, N 2008, 'Consortium analysis of 7 candidate SNPs for ovarian cancer', International Journal of Cancer, vol. 123, no. 2, pp. 380-388. https://doi.org/10.1002/ijc.23448
Ramus SJ, Vierkant RA, Johnatty SE, Pike MC, Van Den Berg DJ, Wu AH et al. Consortium analysis of 7 candidate SNPs for ovarian cancer. International Journal of Cancer. 2008 Jul 15;123(2):380-388. https://doi.org/10.1002/ijc.23448
Ramus, Susan J. ; Vierkant, Robert A. ; Johnatty, Sharon E. ; Pike, Malcolm C. ; Van Den Berg, David J. ; Wu, Anna H. ; Pearce, Celeste Leigh ; Menon, Usha ; Gentry-Maharaj, Aleksandra ; Gayther, Simon A. ; DiCioccio, Richard A. ; McGuire, Valerie ; Whittemore, Alice S. ; Song, Honglin ; Easton, Douglas F. ; Pharoah, Paul D P ; Garcia-Closas, Montserrat ; Chanock, Stephen ; Lissowska, Jolanta ; Brinton, Louise ; Terry, Kathryn L. ; Cramer, Daniel W. ; Tworoger, Shelley S. ; Hankinson, Susan E. ; Berchuck, Andrew ; Moorman, Patricia G. ; Schildkraut, Joellen M. ; Cunningham, Julie M. ; Liebow, Mark ; Kjaer, Susanne Krüger ; Hogdall, Estrid ; Hogdall, Claus ; Blaakaer, Jan ; Ness, Roberta B. ; Moysich, Kirsten B. ; Edwards, Robert P. ; Carney, Michael E. ; Lurie, Galina ; Goodman, Marc T. ; Wang-Gohrke, Shan ; Kropp, Silke ; Chang-Claude, Jenny ; Webb, Penelope M. ; Chen, Xiaoqing ; Beesley, Jonathan ; Chenevix-Trench, Georgia ; Goode, Ellen L. ; Bowtell, D. ; Chenevix-Trench, G. ; Green, A. ; Webb, P. ; DeFazio, A. ; Gertig, D. ; Traficante, N. ; Moore, S. ; Hung, J. ; Fereday, S. ; Harrap, K. ; Sadkowsky, T. ; Mellon, A. ; Robertson, R. ; Vanden Bergh, T. ; Maidens, J. ; Nattress, K. ; Chiew, Y. E. ; Stenlake, A. ; Sullivan, H. ; Alexander, B. ; Ashover, P. ; Brown, S. ; Corrish, T. ; Green, L. ; Jackman, L. ; Martin, K. ; Ranieri, B. ; White, J. ; Jayde, V. ; Bowes, V. L. ; Mamers, P. ; Schmidt, T. ; Shirley, H. ; Viduka, S. ; Tran, H. ; Bilic, S. ; Glavinas, L. ; Proietto, A. ; Braye, S. ; Otton, G. ; Bonaventura, T. ; Stewart, J. ; Friedlander, M. ; Bell, D. ; Baron-Hay, S. ; Ferrier, A. ; Gard, G. ; Nevell, D. ; Young, B. ; Camaris, C. ; Crouch, R. ; Edwards, L. ; Hacker, N. ; Marsden, D. ; Robertson, G. ; Beale, P. ; Beith, J. ; Carter, J. ; Dalrymple, C. ; Hamilton, A. ; Houghton, R. ; Russell, P. ; Brand, A. ; Jaworski, R. ; Harnett, P. ; Wain, G. ; Crandon, A. ; Cummings, M. ; Horwood, K. ; Obermair, A. ; Wyld, D. ; Nicklin, J. ; Papadimos, D. ; Perrin, L. ; Ward, B. ; Davy, M. ; Hall, C. ; Dodd, T. ; Healy, T. ; Pittman, K. ; Henderson, D. ; Hyde, S. ; Miller, J. ; Pierdes, J. ; Blomfield, P. ; Challis, D. ; McIntosh, R. ; Parker, A. ; Brown, B. ; Rome, R. ; Allen, D. ; Grant, P. ; Laurie, R. ; Robbie, M. ; Healy, D. ; Jobling, T. ; Maniolitas, T. ; McNealage, J. ; Rogers, P. ; Susil, B. ; Veitch, A. ; Constable, J. ; Ping Tong, S. ; Robinson, I. ; Simpson, I. ; Phillips, K. ; Rischin, D. ; Waring, P. ; Loughrey, M. ; O'Callaghan, N. ; Murray, Bill ; Billson, V. ; Galloway, S. ; Pyman, J. ; Quinn, M. ; Hammond, I. ; McCartney, A. ; Leung, Y. ; Haviv, I. ; Purdie, D. ; Whiteman, D. ; Zeps, N. / Consortium analysis of 7 candidate SNPs for ovarian cancer. In: International Journal of Cancer. 2008 ; Vol. 123, No. 2. pp. 380-388.
@article{a088477ae406429e9ef0a10f1f6b9c23,
title = "Consortium analysis of 7 candidate SNPs for ovarian cancer",
abstract = "The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95{\%} confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95{\%} CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95{\%} CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95{\%} CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95{\%} CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.",
keywords = "Association study, Neoplasms, Ovarian cancer, Replication, Single nucleotide polymorphism",
author = "Ramus, {Susan J.} and Vierkant, {Robert A.} and Johnatty, {Sharon E.} and Pike, {Malcolm C.} and {Van Den Berg}, {David J.} and Wu, {Anna H.} and Pearce, {Celeste Leigh} and Usha Menon and Aleksandra Gentry-Maharaj and Gayther, {Simon A.} and DiCioccio, {Richard A.} and Valerie McGuire and Whittemore, {Alice S.} and Honglin Song and Easton, {Douglas F.} and Pharoah, {Paul D P} and Montserrat Garcia-Closas and Stephen Chanock and Jolanta Lissowska and Louise Brinton and Terry, {Kathryn L.} and Cramer, {Daniel W.} and Tworoger, {Shelley S.} and Hankinson, {Susan E.} and Andrew Berchuck and Moorman, {Patricia G.} and Schildkraut, {Joellen M.} and Cunningham, {Julie M.} and Mark Liebow and Kjaer, {Susanne Kr{\"u}ger} and Estrid Hogdall and Claus Hogdall and Jan Blaakaer and Ness, {Roberta B.} and Moysich, {Kirsten B.} and Edwards, {Robert P.} and Carney, {Michael E.} and Galina Lurie and Goodman, {Marc T.} and Shan Wang-Gohrke and Silke Kropp and Jenny Chang-Claude and Webb, {Penelope M.} and Xiaoqing Chen and Jonathan Beesley and Georgia Chenevix-Trench and Goode, {Ellen L.} and D. Bowtell and G. Chenevix-Trench and A. Green and P. Webb and A. DeFazio and D. Gertig and N. Traficante and S. Moore and J. Hung and S. Fereday and K. Harrap and T. Sadkowsky and A. Mellon and R. Robertson and {Vanden Bergh}, T. and J. Maidens and K. Nattress and Chiew, {Y. E.} and A. Stenlake and H. Sullivan and B. Alexander and P. Ashover and S. Brown and T. Corrish and L. Green and L. Jackman and K. Martin and B. Ranieri and J. White and V. Jayde and Bowes, {V. L.} and P. Mamers and T. Schmidt and H. Shirley and S. Viduka and H. Tran and S. Bilic and L. Glavinas and A. Proietto and S. Braye and G. Otton and T. Bonaventura and J. Stewart and M. Friedlander and D. Bell and S. Baron-Hay and A. Ferrier and G. Gard and D. Nevell and B. Young and C. Camaris and R. Crouch and L. Edwards and N. Hacker and D. Marsden and G. Robertson and P. Beale and J. Beith and J. Carter and C. Dalrymple and A. Hamilton and R. Houghton and P. Russell and A. Brand and R. Jaworski and P. Harnett and G. Wain and A. Crandon and M. Cummings and K. Horwood and A. Obermair and D. Wyld and J. Nicklin and D. Papadimos and L. Perrin and B. Ward and M. Davy and C. Hall and T. Dodd and T. Healy and K. Pittman and D. Henderson and S. Hyde and J. Miller and J. Pierdes and P. Blomfield and D. Challis and R. McIntosh and A. Parker and B. Brown and R. Rome and D. Allen and P. Grant and R. Laurie and M. Robbie and D. Healy and T. Jobling and T. Maniolitas and J. McNealage and P. Rogers and B. Susil and A. Veitch and J. Constable and {Ping Tong}, S. and I. Robinson and I. Simpson and K. Phillips and D. Rischin and P. Waring and M. Loughrey and N. O'Callaghan and Bill Murray and V. Billson and S. Galloway and J. Pyman and M. Quinn and I. Hammond and A. McCartney and Y. Leung and I. Haviv and D. Purdie and D. Whiteman and N. Zeps",
year = "2008",
month = "7",
day = "15",
doi = "10.1002/ijc.23448",
language = "English (US)",
volume = "123",
pages = "380--388",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Consortium analysis of 7 candidate SNPs for ovarian cancer

AU - Ramus, Susan J.

AU - Vierkant, Robert A.

AU - Johnatty, Sharon E.

AU - Pike, Malcolm C.

AU - Van Den Berg, David J.

AU - Wu, Anna H.

AU - Pearce, Celeste Leigh

AU - Menon, Usha

AU - Gentry-Maharaj, Aleksandra

AU - Gayther, Simon A.

AU - DiCioccio, Richard A.

AU - McGuire, Valerie

AU - Whittemore, Alice S.

AU - Song, Honglin

AU - Easton, Douglas F.

AU - Pharoah, Paul D P

AU - Garcia-Closas, Montserrat

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Terry, Kathryn L.

AU - Cramer, Daniel W.

AU - Tworoger, Shelley S.

AU - Hankinson, Susan E.

AU - Berchuck, Andrew

AU - Moorman, Patricia G.

AU - Schildkraut, Joellen M.

AU - Cunningham, Julie M.

AU - Liebow, Mark

AU - Kjaer, Susanne Krüger

AU - Hogdall, Estrid

AU - Hogdall, Claus

AU - Blaakaer, Jan

AU - Ness, Roberta B.

AU - Moysich, Kirsten B.

AU - Edwards, Robert P.

AU - Carney, Michael E.

AU - Lurie, Galina

AU - Goodman, Marc T.

AU - Wang-Gohrke, Shan

AU - Kropp, Silke

AU - Chang-Claude, Jenny

AU - Webb, Penelope M.

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Chenevix-Trench, Georgia

AU - Goode, Ellen L.

AU - Bowtell, D.

AU - Chenevix-Trench, G.

AU - Green, A.

AU - Webb, P.

AU - DeFazio, A.

AU - Gertig, D.

AU - Traficante, N.

AU - Moore, S.

AU - Hung, J.

AU - Fereday, S.

AU - Harrap, K.

AU - Sadkowsky, T.

AU - Mellon, A.

AU - Robertson, R.

AU - Vanden Bergh, T.

AU - Maidens, J.

AU - Nattress, K.

AU - Chiew, Y. E.

AU - Stenlake, A.

AU - Sullivan, H.

AU - Alexander, B.

AU - Ashover, P.

AU - Brown, S.

AU - Corrish, T.

AU - Green, L.

AU - Jackman, L.

AU - Martin, K.

AU - Ranieri, B.

AU - White, J.

AU - Jayde, V.

AU - Bowes, V. L.

AU - Mamers, P.

AU - Schmidt, T.

AU - Shirley, H.

AU - Viduka, S.

AU - Tran, H.

AU - Bilic, S.

AU - Glavinas, L.

AU - Proietto, A.

AU - Braye, S.

AU - Otton, G.

AU - Bonaventura, T.

AU - Stewart, J.

AU - Friedlander, M.

AU - Bell, D.

AU - Baron-Hay, S.

AU - Ferrier, A.

AU - Gard, G.

AU - Nevell, D.

AU - Young, B.

AU - Camaris, C.

AU - Crouch, R.

AU - Edwards, L.

AU - Hacker, N.

AU - Marsden, D.

AU - Robertson, G.

AU - Beale, P.

AU - Beith, J.

AU - Carter, J.

AU - Dalrymple, C.

AU - Hamilton, A.

AU - Houghton, R.

AU - Russell, P.

AU - Brand, A.

AU - Jaworski, R.

AU - Harnett, P.

AU - Wain, G.

AU - Crandon, A.

AU - Cummings, M.

AU - Horwood, K.

AU - Obermair, A.

AU - Wyld, D.

AU - Nicklin, J.

AU - Papadimos, D.

AU - Perrin, L.

AU - Ward, B.

AU - Davy, M.

AU - Hall, C.

AU - Dodd, T.

AU - Healy, T.

AU - Pittman, K.

AU - Henderson, D.

AU - Hyde, S.

AU - Miller, J.

AU - Pierdes, J.

AU - Blomfield, P.

AU - Challis, D.

AU - McIntosh, R.

AU - Parker, A.

AU - Brown, B.

AU - Rome, R.

AU - Allen, D.

AU - Grant, P.

AU - Laurie, R.

AU - Robbie, M.

AU - Healy, D.

AU - Jobling, T.

AU - Maniolitas, T.

AU - McNealage, J.

AU - Rogers, P.

AU - Susil, B.

AU - Veitch, A.

AU - Constable, J.

AU - Ping Tong, S.

AU - Robinson, I.

AU - Simpson, I.

AU - Phillips, K.

AU - Rischin, D.

AU - Waring, P.

AU - Loughrey, M.

AU - O'Callaghan, N.

AU - Murray, Bill

AU - Billson, V.

AU - Galloway, S.

AU - Pyman, J.

AU - Quinn, M.

AU - Hammond, I.

AU - McCartney, A.

AU - Leung, Y.

AU - Haviv, I.

AU - Purdie, D.

AU - Whiteman, D.

AU - Zeps, N.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.

AB - The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.

KW - Association study

KW - Neoplasms

KW - Ovarian cancer

KW - Replication

KW - Single nucleotide polymorphism

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U2 - 10.1002/ijc.23448

DO - 10.1002/ijc.23448

M3 - Article

VL - 123

SP - 380

EP - 388

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -