LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

Jennifer Permuth-Wey; Donghwa Kim; Ya Yu Tsai; Hui Yi Lin; Y. Ann Chen; Jill Barnholtz-Sloan; Michael J. Birrer; Gregory Bloom; Stephen J. Chanock; Zhihua Chen; Daniel W. Cramer; Julie M. Cunningham; Getachew Dagne; Judith Ebbert-Syfrett; David Fenstermacher; Brooke L. Fridley; Montserrat Garcia-Closas; Simon A. Gayther; William Ge; Aleksandra Gentry-Maharaj; Jesus Gonzalez-Bosquet; Ellen L. Goode; Edwin Iversen; Heather Jim; William Kong; John McLaughlin; Usha Menon; Alvaro N.A. Monteiro; Steven A. Narod; Paul D.P. Pharoah; Catherine M. Phelan; Xiaotao Qu; Susan J. Ramus; Harvey Risch; Joellen M. Schildkraut; Honglin Song; Heather Stockwell; Rebecca Sutphen; Kathryn L. Terry; Jonathan Tyrer; Robert A. Vierkant; Nicolas Wentzensen; Johnathan M. Lancaster; Jin Q. Cheng; Thomas A. Sellers

doi:10.1158/0008-5472.CAN-10-4167

LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

Jennifer Permuth-Wey, Donghwa Kim, Ya Yu Tsai, Hui Yi Lin, Y. Ann Chen, Jill Barnholtz-Sloan, Michael J. Birrer, Gregory Bloom, Stephen J. Chanock, Zhihua Chen, Daniel W. Cramer, Julie M. Cunningham, Getachew Dagne, Judith Ebbert-Syfrett, David Fenstermacher, Brooke L. Fridley, Montserrat Garcia-Closas, Simon A. Gayther, William Ge, Aleksandra Gentry-MaharajJesus Gonzalez-Bosquet, Ellen L. Goode, Edwin Iversen, Heather Jim, William Kong, John McLaughlin, Usha Menon, Alvaro N.A. Monteiro, Steven A. Narod, Paul D.P. Pharoah, Catherine M. Phelan, Xiaotao Qu, Susan J. Ramus, Harvey Risch, Joellen M. Schildkraut, Honglin Song, Heather Stockwell, Rebecca Sutphen, Kathryn L. Terry, Jonathan Tyrer, Robert A. Vierkant, Nicolas Wentzensen, Johnathan M. Lancaster, Jin Q. Cheng, Thomas A. Sellers

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Abstract

Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.

Original language	English (US)
Pages (from-to)	3896-3903
Number of pages	8
Journal	Cancer Research
Volume	71
Issue number	11
DOIs	https://doi.org/10.1158/0008-5472.CAN-10-4167
State	Published - Jun 1 2011
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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Permuth-Wey, J., Kim, D., Tsai, Y. Y., Lin, H. Y., Chen, Y. A., Barnholtz-Sloan, J., Birrer, M. J., Bloom, G., Chanock, S. J., Chen, Z., Cramer, D. W., Cunningham, J. M., Dagne, G., Ebbert-Syfrett, J., Fenstermacher, D., Fridley, B. L., Garcia-Closas, M., Gayther, S. A., Ge, W., ... Sellers, T. A. (2011). LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer. Cancer Research, 71(11), 3896-3903. https://doi.org/10.1158/0008-5472.CAN-10-4167

Permuth-Wey, J, Kim, D, Tsai, YY, Lin, HY, Chen, YA, Barnholtz-Sloan, J, Birrer, MJ, Bloom, G, Chanock, SJ, Chen, Z, Cramer, DW, Cunningham, JM, Dagne, G, Ebbert-Syfrett, J, Fenstermacher, D, Fridley, BL, Garcia-Closas, M, Gayther, SA, Ge, W, Gentry-Maharaj, A, Gonzalez-Bosquet, J, Goode, EL, Iversen, E, Jim, H, Kong, W, McLaughlin, J, Menon, U, Monteiro, ANA, Narod, SA, Pharoah, PDP, Phelan, CM, Qu, X, Ramus, SJ, Risch, H, Schildkraut, JM, Song, H, Stockwell, H, Sutphen, R, Terry, KL, Tyrer, J, Vierkant, RA, Wentzensen, N, Lancaster, JM, Cheng, JQ & Sellers, TA 2011, 'LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer', Cancer Research, vol. 71, no. 11, pp. 3896-3903. https://doi.org/10.1158/0008-5472.CAN-10-4167

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title = "LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer",

abstract = "Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.",

author = "Jennifer Permuth-Wey and Donghwa Kim and Tsai, {Ya Yu} and Lin, {Hui Yi} and Chen, {Y. Ann} and Jill Barnholtz-Sloan and Birrer, {Michael J.} and Gregory Bloom and Chanock, {Stephen J.} and Zhihua Chen and Cramer, {Daniel W.} and Cunningham, {Julie M.} and Getachew Dagne and Judith Ebbert-Syfrett and David Fenstermacher and Fridley, {Brooke L.} and Montserrat Garcia-Closas and Gayther, {Simon A.} and William Ge and Aleksandra Gentry-Maharaj and Jesus Gonzalez-Bosquet and Goode, {Ellen L.} and Edwin Iversen and Heather Jim and William Kong and John McLaughlin and Usha Menon and Monteiro, {Alvaro N.A.} and Narod, {Steven A.} and Pharoah, {Paul D.P.} and Phelan, {Catherine M.} and Xiaotao Qu and Ramus, {Susan J.} and Harvey Risch and Schildkraut, {Joellen M.} and Honglin Song and Heather Stockwell 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 Sellers, {Thomas A.}",

year = "2011",

month = jun,

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doi = "10.1158/0008-5472.CAN-10-4167",

language = "English (US)",

volume = "71",

pages = "3896--3903",

journal = "Cancer Research",

issn = "0008-5472",

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T1 - LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

AU - Permuth-Wey, Jennifer

AU - Kim, Donghwa

AU - Tsai, Ya Yu

AU - Lin, Hui Yi

AU - Chen, Y. Ann

AU - Barnholtz-Sloan, Jill

AU - Birrer, Michael J.

AU - Bloom, Gregory

AU - Chanock, Stephen J.

AU - Chen, Zhihua

AU - Cramer, Daniel W.

AU - Cunningham, Julie M.

AU - Dagne, Getachew

AU - Ebbert-Syfrett, Judith

AU - Fenstermacher, David

AU - Fridley, Brooke L.

AU - Garcia-Closas, Montserrat

AU - Gayther, Simon A.

AU - Ge, William

AU - Gentry-Maharaj, Aleksandra

AU - Gonzalez-Bosquet, Jesus

AU - Goode, Ellen L.

AU - Iversen, Edwin

AU - Jim, Heather

AU - Kong, William

AU - McLaughlin, John

AU - Menon, Usha

AU - Monteiro, Alvaro N.A.

AU - Narod, Steven A.

AU - Pharoah, Paul D.P.

AU - Phelan, Catherine M.

AU - Qu, Xiaotao

AU - Ramus, Susan J.

AU - Risch, Harvey

AU - Schildkraut, Joellen M.

AU - Song, Honglin

AU - Stockwell, Heather

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 - Sellers, Thomas A.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.

AB - Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.

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JO - Cancer Research

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LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

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