title: A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk.
abstract: Disruption of the circadian rhythm has been reported to increase the risk of breast cancer. A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus. In the current study, we found a novel functional SNP (rs3739008) located at 3'UTR of NPAS2 and the C to T changing of the SNP may disrupt the binding of microRNA- (miR-) 17-5p and miR-519e to the 3'UTR of NPAS2. We then typed this SNP in case-control studies of both Chinese and Germany populations to test its putative associations with breast cancer risk. However, we failed to find any significant associations by different genetic models (dominant genetic model, adjusted OR = 1.13, 95% CI = 0.95-1.35 for the Chinese population and adjusted OR = 0.99, 95% CI = 0.85-1.16 for the Germany population). Although we did not find significant associations at population levels from both Chinese and Germany case-control studies, due to the functional relevance of rs3739008 on NASP2 expression, it will be promising to investigate the influence of this variant on clinical characteristics of breast cancer and breast cancer survival.
authors.affiliation: Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Furu
authors.initials: F
authors.lastname: Wang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Rongxi
authors.initials: R
authors.lastname: Yang
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Dieter
authors.initials: D
authors.lastname: Niederacher
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C104264:NPAS2 protein, human