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; 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 Kru¨ger 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; A. Green; 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

doi:10.1002/ijc.23448

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

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 Kru¨ger 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, A. Green, 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

Department of Epidemiology and Environmental Health

University College London
Mayo Clinic Rochester, MN
Post Office Royal Brisbane Hospital
University of Southern California
Roswell Park Cancer Institute
Stanford University
University of Cambridge
National Institutes of Health
Maria Sklodowska-Curie Institute of Oncology
Brigham and Women’s Hospital
Harvard University
Duke University
Danish Cancer Society
University of Copenhagen
Aarhus University
University of Pittsburgh
University of Hawai'i at Mānoa
Ulm University
German Cancer Research Center
Peter Maccallum Cancer Centre
Queensland Institute of Medical Research
Westmead Hospital
University of Melbourne
Hunter New England Health
Royal Hospital for Women
Royal North Shore Hospital
Royal Prince Alfred Hospital
Royal Hobart Hospital
Monash Medical Centre
Western Australia Research Tissue Network
Newcastle Mater Misericordiae
Prince of Wales Hospital
UnitingCare Health
Sullivan Nicolaides Pathology
Mater Misericordiae Hospital
Royal Adelaide Hospital
Flinders Medical Centre
Mercy Hospital for Women
Queen Elizabeth Hospital Australia
Epworth HealthCare
Royal Women's Hospital
King Edward Memorial Hospital for Women

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

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 language	English
Pages (from-to)	380-388
Number of pages	9
Journal	International Journal of Cancer
Volume	123
Issue number	2
DOIs	https://doi.org/10.1002/ijc.23448
State	Published - Jul 15 2008

Keywords

Association study
Neoplasms
Ovarian cancer
Replication
Single nucleotide polymorphism

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10.1002/ijc.23448

Cite this

Ramus, S. J., Vierkant, R. A., Johnatty, S. E., Pike, M. C., Van Den Berg, D. J., Wu, A. H., Pearce, C. L., Menon, U., Gentry-Maharaj, A., Gayther, S. A., DiCioccio, R. A., McGuire, V., Whittemore, A. S., Song, H., Easton, D. F., Pharoah, P. D. P., Garcia-Closas, M., Chanock, S., Lissowska, J., ... 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

@article{3ab7da2c7d2e4f28aabb1c7408a84a4b,

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 Kru¨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 A. Green 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 = jul,

day = "15",

doi = "10.1002/ijc.23448",

language = "English",

volume = "123",

pages = "380--388",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "John Wiley and Sons Inc",

number = "2",

}

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, Green, A, 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

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 Kru¨ger

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 - Green, A.

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

UR - https://www.scopus.com/pages/publications/44949145237

U2 - 10.1002/ijc.23448

DO - 10.1002/ijc.23448

M3 - Article

C2 - 18431743

AN - SCOPUS:44949145237

SN - 0020-7136

VL - 123

SP - 380

EP - 388

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 2

ER -

Consortium analysis of 7 candidate SNPs for ovarian cancer

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