Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

Honglin Song, Susan J. Ramus, Susanne Krüger Kjaer, Richard A. DiCioccio, Georgia Chenevix-Trench, Celeste Leigh Pearce, Estrid Hogdall, Alice S. Whittemore, Valerie McGuire, Claus Hogdall, Jan Blaakaer, Anna H. Wu, David J. Van Den Berg, Daniel O. Stram, Usha Menon, Aleksandra Gentry-Maharaj, Ian J. Jacobs, Penny M. Webb, Jonathan Beesley, Xiaoqing Chen & 29 others Mary Anne Rossing, Jennifer A. Doherty, Jenny Chang-Claude, Shan Wang-Gohrke, Marc T. Goodman, Galina Lurie, Pamela J. Thompson, Michael E. Carney, Roberta B. Ness, Kirsten Moysich, Ellen L. Goode, Robert A. Vierkant, Julie M. Cunningham, Stephanie Anderson, Joellen M. Schildkraut, Andrew Berchuck, Edwin S. Iversen, Patricia G. Moorman, Montserrat Garcia-Closas, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Hoda Anton-Culver, Argyrios Ziogas, Wendy R. Brewster, Bruce A J Ponder, Douglas F. Easton, Simon A. Gayther, Paul D P Pharoah

Research output: Contribution to journalArticle

Abstract

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend <0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

Original languageEnglish (US)
Pages (from-to)2297-2304
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number12
DOIs
StatePublished - 2009
Externally publishedYes

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Genome-Wide Association Study
Ovarian Neoplasms
Single Nucleotide Polymorphism
Breast Neoplasms
Logistic Models
Odds Ratio
Case-Control Studies
Alleles
Genotype
Hormones

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Song, H., Ramus, S. J., Kjaer, S. K., DiCioccio, R. A., Chenevix-Trench, G., Pearce, C. L., ... Pharoah, P. D. P. (2009). Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study. Human Molecular Genetics, 18(12), 2297-2304. https://doi.org/10.1093/hmg/ddp138

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study. / Song, Honglin; Ramus, Susan J.; Kjaer, Susanne Krüger; DiCioccio, Richard A.; Chenevix-Trench, Georgia; Pearce, Celeste Leigh; Hogdall, Estrid; Whittemore, Alice S.; McGuire, Valerie; Hogdall, Claus; Blaakaer, Jan; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.; Menon, Usha; Gentry-Maharaj, Aleksandra; Jacobs, Ian J.; Webb, Penny M.; Beesley, Jonathan; Chen, Xiaoqing; Rossing, Mary Anne; Doherty, Jennifer A.; Chang-Claude, Jenny; Wang-Gohrke, Shan; Goodman, Marc T.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Ness, Roberta B.; Moysich, Kirsten; Goode, Ellen L.; Vierkant, Robert A.; Cunningham, Julie M.; Anderson, Stephanie; Schildkraut, Joellen M.; Berchuck, Andrew; Iversen, Edwin S.; Moorman, Patricia G.; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Brinton, Louise; Anton-Culver, Hoda; Ziogas, Argyrios; Brewster, Wendy R.; Ponder, Bruce A J; Easton, Douglas F.; Gayther, Simon A.; Pharoah, Paul D P.

In: Human Molecular Genetics, Vol. 18, No. 12, 2009, p. 2297-2304.

Research output: Contribution to journalArticle

Song, H, Ramus, SJ, Kjaer, SK, DiCioccio, RA, Chenevix-Trench, G, Pearce, CL, Hogdall, E, Whittemore, AS, McGuire, V, Hogdall, C, Blaakaer, J, Wu, AH, Van Den Berg, DJ, Stram, DO, Menon, U, Gentry-Maharaj, A, Jacobs, IJ, Webb, PM, Beesley, J, Chen, X, Rossing, MA, Doherty, JA, Chang-Claude, J, Wang-Gohrke, S, Goodman, MT, Lurie, G, Thompson, PJ, Carney, ME, Ness, RB, Moysich, K, Goode, EL, Vierkant, RA, Cunningham, JM, Anderson, S, Schildkraut, JM, Berchuck, A, Iversen, ES, Moorman, PG, Garcia-Closas, M, Chanock, S, Lissowska, J, Brinton, L, Anton-Culver, H, Ziogas, A, Brewster, WR, Ponder, BAJ, Easton, DF, Gayther, SA & Pharoah, PDP 2009, 'Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study', Human Molecular Genetics, vol. 18, no. 12, pp. 2297-2304. https://doi.org/10.1093/hmg/ddp138
Song, Honglin ; Ramus, Susan J. ; Kjaer, Susanne Krüger ; DiCioccio, Richard A. ; Chenevix-Trench, Georgia ; Pearce, Celeste Leigh ; Hogdall, Estrid ; Whittemore, Alice S. ; McGuire, Valerie ; Hogdall, Claus ; Blaakaer, Jan ; Wu, Anna H. ; Van Den Berg, David J. ; Stram, Daniel O. ; Menon, Usha ; Gentry-Maharaj, Aleksandra ; Jacobs, Ian J. ; Webb, Penny M. ; Beesley, Jonathan ; Chen, Xiaoqing ; Rossing, Mary Anne ; Doherty, Jennifer A. ; Chang-Claude, Jenny ; Wang-Gohrke, Shan ; Goodman, Marc T. ; Lurie, Galina ; Thompson, Pamela J. ; Carney, Michael E. ; Ness, Roberta B. ; Moysich, Kirsten ; Goode, Ellen L. ; Vierkant, Robert A. ; Cunningham, Julie M. ; Anderson, Stephanie ; Schildkraut, Joellen M. ; Berchuck, Andrew ; Iversen, Edwin S. ; Moorman, Patricia G. ; Garcia-Closas, Montserrat ; Chanock, Stephen ; Lissowska, Jolanta ; Brinton, Louise ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Brewster, Wendy R. ; Ponder, Bruce A J ; Easton, Douglas F. ; Gayther, Simon A. ; Pharoah, Paul D P. / Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 12. pp. 2297-2304.
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abstract = "Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend <0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95{\%} CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95{\%} CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.",
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T1 - Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

AU - Song, Honglin

AU - Ramus, Susan J.

AU - Kjaer, Susanne Krüger

AU - DiCioccio, Richard A.

AU - Chenevix-Trench, Georgia

AU - Pearce, Celeste Leigh

AU - Hogdall, Estrid

AU - Whittemore, Alice S.

AU - McGuire, Valerie

AU - Hogdall, Claus

AU - Blaakaer, Jan

AU - Wu, Anna H.

AU - Van Den Berg, David J.

AU - Stram, Daniel O.

AU - Menon, Usha

AU - Gentry-Maharaj, Aleksandra

AU - Jacobs, Ian J.

AU - Webb, Penny M.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Rossing, Mary Anne

AU - Doherty, Jennifer A.

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Goodman, Marc T.

AU - Lurie, Galina

AU - Thompson, Pamela J.

AU - Carney, Michael E.

AU - Ness, Roberta B.

AU - Moysich, Kirsten

AU - Goode, Ellen L.

AU - Vierkant, Robert A.

AU - Cunningham, Julie M.

AU - Anderson, Stephanie

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Iversen, Edwin S.

AU - Moorman, Patricia G.

AU - Garcia-Closas, Montserrat

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Brewster, Wendy R.

AU - Ponder, Bruce A J

AU - Easton, Douglas F.

AU - Gayther, Simon A.

AU - Pharoah, Paul D P

PY - 2009

Y1 - 2009

N2 - Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend <0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

AB - Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend <0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

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