Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set

Jonathan Beesley; Susan J. Jordan; Amanda B. Spurdle; Honglin Song; Susan J. Ramus; Suzanne Kruger Kjaer; Estrid Hogdall; Richard A. DiCioccio; Valerie McGuire; Alice S. Whittemore; Simon A. Gayther; Paul D.P. Pharoah; Penelope M. Webb; Georgia Chenevix-Trench; 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; L. Bowes; P. Mamers; T. Schmidt; H. Shirley; S. Viduka; Hoa Tran; Sanela Bilic; Lydia 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; 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:10.1158/1055-9965.EPI-07-0542

Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set

Jonathan Beesley, Susan J. Jordan, Amanda B. Spurdle, Honglin Song, Susan J. Ramus, Suzanne Kruger Kjaer, Estrid Hogdall, Richard A. DiCioccio, Valerie McGuire, Alice S. Whittemore, Simon A. Gayther, Paul D.P. Pharoah, Penelope M. Webb, Georgia Chenevix-Trench, D. Bowtell, A. Green, A. DeFazio, D. Gertig, N. Traficante, S. MooreJ. 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, L. Bowes, P. Mamers, T. Schmidt, H. Shirley, S. Viduka, Hoa Tran, Sanela Bilic, Lydia 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, 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 journal › Article › peer-review

65 Scopus citations

Abstract

Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r² = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition.

Original language	English (US)
Pages (from-to)	2557-2565
Number of pages	9
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	16
Issue number	12
DOIs	https://doi.org/10.1158/1055-9965.EPI-07-0542
State	Published - Dec 1 2007
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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10.1158/1055-9965.EPI-07-0542

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Beesley, J., Jordan, S. J., Spurdle, A. B., Song, H., Ramus, S. J., Kjaer, S. K., Hogdall, E., DiCioccio, R. A., McGuire, V., Whittemore, A. S., Gayther, S. A., Pharoah, P. D. P., Webb, P. M., Chenevix-Trench, G., Bowtell, D., Green, A., DeFazio, A., Gertig, D., Traficante, N., ... Zeps, N. (2007). Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set. Cancer Epidemiology Biomarkers and Prevention, 16(12), 2557-2565. https://doi.org/10.1158/1055-9965.EPI-07-0542

Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set. / Beesley, Jonathan; Jordan, Susan J.; Spurdle, Amanda B. et al.
In: Cancer Epidemiology Biomarkers and Prevention, Vol. 16, No. 12, 01.12.2007, p. 2557-2565.

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

Beesley, J, Jordan, SJ, Spurdle, AB, Song, H, Ramus, SJ, Kjaer, SK, Hogdall, E, DiCioccio, RA, McGuire, V, Whittemore, AS, Gayther, SA, Pharoah, PDP, Webb, PM, Chenevix-Trench, G, 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, 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, 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, Tong, SP, 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 2007, 'Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set', Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 12, pp. 2557-2565. https://doi.org/10.1158/1055-9965.EPI-07-0542

Beesley J, Jordan SJ, Spurdle AB, Song H, Ramus SJ, Kjaer SK et al. Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set. Cancer Epidemiology Biomarkers and Prevention. 2007 Dec 1;16(12):2557-2565. doi: 10.1158/1055-9965.EPI-07-0542

@article{33e5afa9d1834270889426cfe536d84b,

title = "Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set",

abstract = "Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition.",

author = "Jonathan Beesley and Jordan, {Susan J.} and Spurdle, {Amanda B.} and Honglin Song and Ramus, {Susan J.} and Kjaer, {Suzanne Kruger} and Estrid Hogdall and DiCioccio, {Richard A.} and Valerie McGuire and Whittemore, {Alice S.} and Gayther, {Simon A.} and Pharoah, {Paul D.P.} and Webb, {Penelope M.} and Georgia Chenevix-Trench 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 L. Bowes and P. Mamers and T. Schmidt and H. Shirley and S. Viduka and Hoa Tran and Sanela Bilic and Lydia 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 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 Tong, {S. Ping} 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",

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doi = "10.1158/1055-9965.EPI-07-0542",

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T1 - Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer

T2 - Results from two Australian studies and an additional validation set

AU - Beesley, Jonathan

AU - Jordan, Susan J.

AU - Spurdle, Amanda B.

AU - Song, Honglin

AU - Ramus, Susan J.

AU - Kjaer, Suzanne Kruger

AU - Hogdall, Estrid

AU - DiCioccio, Richard A.

AU - McGuire, Valerie

AU - Whittemore, Alice S.

AU - Gayther, Simon A.

AU - Pharoah, Paul D.P.

AU - Webb, Penelope M.

AU - Chenevix-Trench, Georgia

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, L.

AU - Mamers, P.

AU - Schmidt, T.

AU - Shirley, H.

AU - Viduka, S.

AU - Tran, Hoa

AU - Bilic, Sanela

AU - Glavinas, Lydia

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 - 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 - Tong, S. Ping

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 - 2007/12/1

Y1 - 2007/12/1

N2 - Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition.

AB - Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition.

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ER -

Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set

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