MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium

Jennifer Permuth-Wey, Zhihua Chen, Ya Yu Tsai, Hui Yi Lin, Y. Ann Chen, Jill Barnholtz-Sloan, Michael J. Birrer, Stephen J. Chanock, Daniel W. Cramer, Julie M Cunningham, David Fenstermacher, Brooke L. Fridley, Montserrat Garcia-Closas, Simon A. Gayther, Aleksandra Gentry-Maharaj, Jesus Gonzalez-Bosquet, Edwin Iversen, Heather Jim, John McLaughlin, Usha Menon & 17 others Steven A. Narod, Catherine M. Phelan, Susan J. Ramus, Harvey Risch, Honglin Song, Rebecca Sutphen, Kathryn L. Terry, Jonathan Tyrer, Robert A. Vierkant, Nicolas Wentzensen, Johnathan M. Lancaster, Jin Q. Cheng, Andrew Berchuck, Paul D P Pharoah, Joellen M. Schildkraut, Ellen L Goode, Thomas A. Sellers

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Commonvariants in these evaluated genesdonotseemto be strongly associatedwithEOCrisk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered.

Original languageEnglish (US)
Pages (from-to)1793-1797
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number8
DOIs
StatePublished - Aug 2011

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MicroRNAs
Ovarian Neoplasms
Single Nucleotide Polymorphism
Binding Sites
Genes
Genotype
Sample Size
Population
Alleles
Ovarian epithelial cancer
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium. / Permuth-Wey, Jennifer; Chen, Zhihua; Tsai, Ya Yu; Lin, Hui Yi; Chen, Y. Ann; Barnholtz-Sloan, Jill; Birrer, Michael J.; Chanock, Stephen J.; Cramer, Daniel W.; Cunningham, Julie M; Fenstermacher, David; Fridley, Brooke L.; Garcia-Closas, Montserrat; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gonzalez-Bosquet, Jesus; Iversen, Edwin; Jim, Heather; McLaughlin, John; Menon, Usha; Narod, Steven A.; Phelan, Catherine M.; Ramus, Susan J.; Risch, Harvey; Song, Honglin; Sutphen, Rebecca; Terry, Kathryn L.; Tyrer, Jonathan; Vierkant, Robert A.; Wentzensen, Nicolas; Lancaster, Johnathan M.; Cheng, Jin Q.; Berchuck, Andrew; Pharoah, Paul D P; Schildkraut, Joellen M.; Goode, Ellen L; Sellers, Thomas A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 8, 08.2011, p. 1793-1797.

Research output: Contribution to journalArticle

Permuth-Wey, J, Chen, Z, Tsai, YY, Lin, HY, Chen, YA, Barnholtz-Sloan, J, Birrer, MJ, Chanock, SJ, Cramer, DW, Cunningham, JM, Fenstermacher, D, Fridley, BL, Garcia-Closas, M, Gayther, SA, Gentry-Maharaj, A, Gonzalez-Bosquet, J, Iversen, E, Jim, H, McLaughlin, J, Menon, U, Narod, SA, Phelan, CM, Ramus, SJ, Risch, H, Song, H, Sutphen, R, Terry, KL, Tyrer, J, Vierkant, RA, Wentzensen, N, Lancaster, JM, Cheng, JQ, Berchuck, A, Pharoah, PDP, Schildkraut, JM, Goode, EL & Sellers, TA 2011, 'MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 8, pp. 1793-1797. https://doi.org/10.1158/1055-9965.EPI-11-0397
Permuth-Wey, Jennifer ; Chen, Zhihua ; Tsai, Ya Yu ; Lin, Hui Yi ; Chen, Y. Ann ; Barnholtz-Sloan, Jill ; Birrer, Michael J. ; Chanock, Stephen J. ; Cramer, Daniel W. ; Cunningham, Julie M ; Fenstermacher, David ; Fridley, Brooke L. ; Garcia-Closas, Montserrat ; Gayther, Simon A. ; Gentry-Maharaj, Aleksandra ; Gonzalez-Bosquet, Jesus ; Iversen, Edwin ; Jim, Heather ; McLaughlin, John ; Menon, Usha ; Narod, Steven A. ; Phelan, Catherine M. ; Ramus, Susan J. ; Risch, Harvey ; Song, Honglin ; Sutphen, Rebecca ; Terry, Kathryn L. ; Tyrer, Jonathan ; Vierkant, Robert A. ; Wentzensen, Nicolas ; Lancaster, Johnathan M. ; Cheng, Jin Q. ; Berchuck, Andrew ; Pharoah, Paul D P ; Schildkraut, Joellen M. ; Goode, Ellen L ; Sellers, Thomas A. / MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 8. pp. 1793-1797.
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abstract = "Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Commonvariants in these evaluated genesdonotseemto be strongly associatedwithEOCrisk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered.",
author = "Jennifer Permuth-Wey and Zhihua Chen and Tsai, {Ya Yu} and Lin, {Hui Yi} and Chen, {Y. Ann} and Jill Barnholtz-Sloan and Birrer, {Michael J.} and Chanock, {Stephen J.} and Cramer, {Daniel W.} and Cunningham, {Julie M} and David Fenstermacher and Fridley, {Brooke L.} and Montserrat Garcia-Closas and Gayther, {Simon A.} and Aleksandra Gentry-Maharaj and Jesus Gonzalez-Bosquet and Edwin Iversen and Heather Jim and John McLaughlin and Usha Menon and Narod, {Steven A.} and Phelan, {Catherine M.} and Ramus, {Susan J.} and Harvey Risch and Honglin Song and Rebecca Sutphen and Terry, {Kathryn L.} and Jonathan Tyrer and Vierkant, {Robert A.} and Nicolas Wentzensen and Lancaster, {Johnathan M.} and Cheng, {Jin Q.} and Andrew Berchuck and Pharoah, {Paul D P} and Schildkraut, {Joellen M.} and Goode, {Ellen L} and Sellers, {Thomas A.}",
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T1 - MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium

AU - Permuth-Wey, Jennifer

AU - Chen, Zhihua

AU - Tsai, Ya Yu

AU - Lin, Hui Yi

AU - Chen, Y. Ann

AU - Barnholtz-Sloan, Jill

AU - Birrer, Michael J.

AU - Chanock, Stephen J.

AU - Cramer, Daniel W.

AU - Cunningham, Julie M

AU - Fenstermacher, David

AU - Fridley, Brooke L.

AU - Garcia-Closas, Montserrat

AU - Gayther, Simon A.

AU - Gentry-Maharaj, Aleksandra

AU - Gonzalez-Bosquet, Jesus

AU - Iversen, Edwin

AU - Jim, Heather

AU - McLaughlin, John

AU - Menon, Usha

AU - Narod, Steven A.

AU - Phelan, Catherine M.

AU - Ramus, Susan J.

AU - Risch, Harvey

AU - Song, Honglin

AU - Sutphen, Rebecca

AU - Terry, Kathryn L.

AU - Tyrer, Jonathan

AU - Vierkant, Robert A.

AU - Wentzensen, Nicolas

AU - Lancaster, Johnathan M.

AU - Cheng, Jin Q.

AU - Berchuck, Andrew

AU - Pharoah, Paul D P

AU - Schildkraut, Joellen M.

AU - Goode, Ellen L

AU - Sellers, Thomas A.

PY - 2011/8

Y1 - 2011/8

N2 - Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Commonvariants in these evaluated genesdonotseemto be strongly associatedwithEOCrisk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered.

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