Association of common WRAP 53 variant with ovarian cancer risk in the Polish population

Abstract

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogensis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53–TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53–WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.

On the road with WRAP53β: guardian of Cajal bodies and genome integrity

“…Single nucleotide polymorphisms (SNPs) in the WRAP53 gene have been linked to an increased risk for breast and ovarian cancer (Garcia-Closas et al, 2007 ; Schildkraut et al, 2009 ; Medrek et al, 2013 ). One of these SNPs is also associated with defective DNA repair and hematotoxicity in workers exposed to benzene.…”

The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair

“…For example, inherited mutations in WRAP53b that affect its WD40 domain cause dyskeratosis congenita, a disorder involving bone marrow failure, premature aging, and cancer predisposition (Zhong et al 2011). Moreover, SNPs in WRAP53 or altered expression of the protein itself are associated with elevated risk for a variety of sporadic tumors and radioresistant head and neck cancer cells, hematoxicity, and disturbed DNA repair in workers exposed to benzene (Garcia-Closas et al 2007;Lan et al 2009;Schildkraut et al 2009;Mahmoudi et al 2011;Medrek et al 2013;Garvin et al 2014). Furthermore, patients with spinal muscular atrophy, a neurodegenerative disorder that is the leading genetic cause of infant mortality worldwide, exhibit loss of WRAP53b function (Mahmoudi et al 2010).…”

Association between the WRAP53 gene rs2287499 C>G polymorphism and cancer risk: A meta-analysis

“…Mędrek et al (2013) found WRAP53 to be associated with ovarian cancer risk in a Polish population, although only in relation to its rs2287497 and rs2287498 polymorphisms. In addition, Garcia-Closas et al (2007) established a significant association between rs2287499 and breast cancer.…”

“…Single nucleotide polymorphisms (SNPs) have been confirmed to play important roles in the etiology of cancer and are therefore of great interest in this field. However, as opinions vary in regard to the significance of WRAP53 SNPs, no unanimous conclusion can be drawn (Lan et al, 2009;Schildkraut et al, 2009;Rizzato et al, 2011;Mędrek et al, 2013;Saldaña-Meyer et al, 2014;Garvin et al, 2015). With this in mind, we performed the current meta-analysis to explore the relationship between the common non-synonymous C>G SNP in the first coding exon of WRAP53 (Arg68Gly) and risk of cancer.…”