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; on behalf of the Ovarian Cancer Association Consortium (OCAC)

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

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LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer

Journal article

Open access

Peer reviewed

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, …

Cancer research, Vol.71(11), pp.3896-3903

06/01/2011

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

PMCID: PMC3107389

PMID: 21482675

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Abstract

Defective miRNA biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNPs) 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), a 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 over-expression 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 due to reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.

Ovarian Cancer

genetic variants

inherited susceptibility

miRNA processing

Details

Title: Subtitle: LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer
Creators: Jennifer Permuth-Wey - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Donghwa Kim - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Ya-Yu Tsai - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Hui-Yi Lin - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Y Ann Chen - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Jill Barnholtz-Sloan - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Michael J Birrer - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Gregory Bloom - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Stephen J Chanock - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Zhihua Chen
Daniel W Cramer - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Julie M Cunningham - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Getachew Dagne - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Judith Ebbert-Syfrett - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
David Fenstermacher - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Brooke L Fridley - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Montserrat Garcia-Closas - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Simon A Gayther - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
William Ge - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Aleksandra Gentry-Maharaj - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Jesus Gonzalez-Bosquet - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Ellen L Goode - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Edwin Iversen - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Heather Jim - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
William Kong - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
John McLaughlin - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Usha Menon - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Alvaro N.A Monteiro - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Steven A Narod - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Paul D.P Pharoah - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Catherine M Phelan - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Xiaotao Qu - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Susan J Ramus - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Harvey Risch - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Joellen M Schildkraut - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Honglin Song - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Heather Stockwell - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Rebecca Sutphen - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Kathryn L Terry - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Jonathan Tyrer - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Robert A Vierkant - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Nicolas Wentzensen - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Johnathan M Lancaster - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Jin Q Cheng - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
Thomas A Sellers - Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA
on behalf of the Ovarian Cancer Association Consortium (OCAC)
Resource Type: Journal article
Publication Details: Cancer research, Vol.71(11), pp.3896-3903
DOI: 10.1158/0008-5472.CAN-10-4167
PMID: 21482675
PMCID: PMC3107389
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: R01 CA114343-01A2 || CA / National Cancer Institute : NCI
Language: English
Date published: 06/01/2011
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983931745302771

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