Rrp1B gene polymorphism (1307T>C) in metastatic progression of breast cancer

Abstract

Rrp1B (ribosomal RNA processing1 homolog B) is a novel candidate metastasis modifier gene in breast cancer. Functional gene assays demonstrated that a physical and functional interaction existing between Rrp1b and metastasis modifier gene SIPA1 causes reduction in the tumor growth and metastatic potential. Ectopic expression of Rrp1B modulates various metastasis predictive extra cellular matrix (ECM) genes associated with tumor suppression. The aim of this study is to determine the functional significance of single nucleotide polymorphism (SNP) in human Rrp1B gene (1307 T>C; rs9306160) with breast cancer development and progression. The study consists of 493 breast cancer cases recruited from Nizam's Institute of Medical Sciences, Hyderabad, and 558 age-matched healthy female controls from rural and urban areas. Genomic DNA was isolated by non-enzymatic method. Genotyping was done by amplification refractory mutation system (ARMS-PCR) method. Genotypes were reconfirmed by sequencing and results were analyzed statistically. We have performed Insilco analysis to know the RNA secondary structure by using online tool m fold. The TT genotype and T allele frequencies of Rrp1B1307 T>C polymorphism were significantly elevated in breast cancer (χ (2); p = <0.008) cases compared to controls under different genetic models. The presence of T allele had conferred 1.75-fold risk for breast cancer development (OR = 1.75; 95% CI = 1.15-2.67). The frequency of TT genotype of Rrp1b 1307T>C polymorphism was significantly elevated in obese patients (χ (2); p = 0.008) and patients with advanced disease (χ (2); p = 0.01) and with increased tumor size (χ (2); p = 0.01). Moreover, elevated frequency of T allele was also associated with positive lymph node status (χ (2); p = 0.04) and Her2 negative receptor status (χ (2); p = 0.006). Presence of Rrp1b1307TT genotype and T allele confer strong risk for breast cancer development and progression.

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

“…RRP1B is another gene that significantly correlated with poor survival in TCGA, yet the gene is believed to interact with metastasis modifier genes to induce tumor suppression. [67, 68] It is important to note that the expression relationship of genes with cancer incidence cannot be translated directly to be equivalent to cancer prognosis. Our findings for TDG and RRP1B indicate that the two genes may possess unknown in vivo interactions that are associated with improved survival.…”

Genetic insights into the morass of metastatic heterogeneity

“…A polymorphism in the proximal promoter region of SIPA1 that reduces SIPA1 transcriptional activity in humans 101 was found to be associated with improved breast cancer survival 97 , which is consistent with the experimental mouse studies. Similarly, a polymorphism that encodes an amino acid substitution in RRP1B was found to be associated with survival, with patients with breast cancer carrying this rarer allelic variant being less likely to develop distant metastatic disease 92,100 . The results of these studies suggest that polymorphisms in the human population contribute to the metastatic susceptibility and heterogeneity observed across the human population and validate the experimental approach in mice.…”

Clinicopathological significance and biological role of TCF21 mRNA in breast cancer

“…For example, a single nucleotide polymorphism (1307 T>C; rs9306160) in human ribosomal RNA processing1 homolog B (Rrp1B) gene was associated with the development and progression of breast cancer. The frequency of TT genotype of Rrp1B1307T>C polymorphism was significantly elevated in patients with advanced disease [3]. The largest subunit of remodeling and spacing factor (RSF), Rsf-1, mediates ATPasedependent chromatin remodeling.…”