Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene

Abstract

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene

“…Additionally, the varying allele frequencies among different ethnicities, geographies and populations may yield conflicting results regarding IGFBP3 polymorphisms and cancer risk. A large-scale urinary bladder cancer study based on a multiethnic population residing in Germany and Hungary demonstrated that the C allele (55%) was slightly more frequent than the A allele (45%) at the − 202 site of the IGFBP-3 gene [ 19 ], which was significantly different from our participants’ allele distributions. However, a cancer study involving Korean and Japanese [ 20 ] adults indicated that the A allele (65–80%) was appreciably more frequent than the C allele (20–35%) and that the C allele was correlated with a reduced non-small cell lung cancer risk [ 21 ].…”

Gene Expression Profiling of Early Hepatic Stellate Cell Activation Reveals a Role for Igfbp3 in Cell Migration

“…From previous studies we know that histone deacetylase (HDAC) inhibitors, like valproic acid (VPA), can maintain these cells in a more quiescent state [13] and reduce fibrogenesis in animal models for liver, kidney and heart fibrosis [14]. HDACs are enzymes involved in chromatin remodeling and in gene expression alterations [15]. In this study we chose to compare the gene expression profiles of in vitro cultured cells in normal conditions to those treated with VPA, in order to identify genes involved in the earliest stages of the activation of freshly isolated mouse HSCs.…”

Genetic variation in IGF1 predicts renal cell carcinoma susceptibility and prognosis in Chinese population

“…The IGFBP3 rs2854744 polymorphism has been studied in different cancers such as esophageal squamous cell carcinoma29, breast cancer30, colorectal cancer31, and urinary bladder cancer32. The polymorphism is located in the gene promoter and may have an effect on the binding affinity of transcription factors to the promoter, which would lead to changes in gene expression.…”