Abstract
SENP proteases take part in post-translational modification of proteins known as sumoylation. They catalyze three distinct processes during sumoylation: processing of SUMO protein, deconjugation of SUMO from the target protein, and chain editing which mentions to the dismantling of SUMO chain. Many proteins that are involved in the basic processes of cells, such as regulation of transcription, DNA repair or cell cycle control, are sumoylated. The aim of these studies was to investigate an association between polymorphic variants (SNPs) of the SENP1 gene (c.1691 + 36C > T, rs12297820) and SENP2 gene (c.902C > A, p.Thr301Lys, rs6762208) and a risk of breast cancer occurrence. We performed a case-control study in 324 breast cancer cases and 335 controls using PCR-RLFP. In the case of the SENP1 gene polymorphism we did not find any association between this polymorphism and breast cancer risk. In the case of SENP2 gene polymorphism we observed higher risk of breast cancer for carriers of the A allele (OR =1.33; 95 % CI 1.04–1.69). Our analysis also showed the genotype C/C (OR =0.67, 95 % CI 0.48–0.93) and the allele C (OR =0.75, 95 % CI 0.59–0.69) of this polymorphism decrease a risk of breast cancer. We also checked the distribution of genotypes and frequency of alleles of the SENP1 and SENP2 genes polymorphisms in groups of patients with different hormone receptor status, patients with positive and negative lymph node status and patients with different tumor grade. Odds ratio analysis showed a higher risk of metastases in women with the genotype C/C (OR =2.07, 95 % CI 1.06–4.05) and allele C (OR =2.10 95 % CI 1.10–4.01) of the c.1691 + 36C > T SENP1 gene polymorphism. Moreover, we observed reduced risk in women with the allele T (OR =0.48, 95 % CI 0.25–0.91) in this polymorphic site. In the case of SENP2 gene polymorphism we observed that the A/A genotype correlated with the lack of estrogen receptor (OR =1.94, 95 % CI 1.04–3.62). Our results suggest that the variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence. Further studies are needed to clarify their biological functions in breast cancer.
Highlights
Small ubiquitin-like modifiers (SUMO) conjugation to proteins is a reversible post-translational modification, which may affect the function, sub-cellular localization and expression of proteins
Our results suggest that the variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence
We studied an association between the polymorphisms of the SENP1 and SENP2 genes and clinical characteristics of breast cancer patients such as lymph node status, tumor grade, hormone receptors and epidermal growth factor receptor (HER2) expression
Summary
Small ubiquitin-like modifiers (SUMO) conjugation to proteins is a reversible post-translational modification, which may affect the function, sub-cellular localization and expression of proteins. Proteins, which are sumoylated take part in many cellular processes including regulation of transcription, DNA repair, nuclear transport and cell cycle control. Posttranslational modification of proteins by SUMO-4 is questionable, as it remains in the inactive form in vivo [1, 2]. SUMO2/3 efficiently forms polymeric chains while in contrast SUMO-1 creates polymeric chains rarely. SUMO modification is a highly dynamic process, catalyzed by SUMOspecific activating (E1), conjugating (E2) and ligating (E3) enzymes. Sumoylation of target proteins results in the formation of isopeptide (amide) bond between the Cterminal glycine of SUMO and the ε-amino group of lysine within the target proteins [2]
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