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.
authors.affiliation: Cancer Epidemiology Program, Division of Population Sciences, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.forename: Donghwa
authors.initials: D
authors.lastname: Kim
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Tsai
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Y Ann
authors.initials: YA
authors.lastname: Chen
authors.forename: Jill
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authors.lastname: Barnholtz-Sloan
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authors.initials: MJ
authors.lastname: Birrer
authors.forename: Gregory
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authors.lastname: Bloom
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authors.initials: SJ
authors.lastname: Chanock
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.forename: Daniel W
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authors.lastname: Cramer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Getachew
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authors.lastname: Dagne
authors.forename: Judith
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authors.lastname: Ebbert-Syfrett
authors.forename: David
authors.initials: D
authors.lastname: Fenstermacher
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Montserrat
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authors.lastname: Garcia-Closas
authors.forename: Simon A
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authors.lastname: Gayther
authors.forename: William
authors.initials: W
authors.lastname: Ge
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Jesus
authors.initials: J
authors.lastname: Gonzalez-Bosquet
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Edwin
authors.initials: E
authors.lastname: Iversen
authors.forename: Heather
authors.initials: H
authors.lastname: Jim
authors.forename: William
authors.initials: W
authors.lastname: Kong
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Alvaro N A
authors.initials: AN
authors.lastname: Monteiro
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Qu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Heather
authors.initials: H
authors.lastname: Stockwell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sutphen
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tyrer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics*; D000483:Alleles; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D014162:Transfection
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins