GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population.

Autor: Belyavskaya VA; Research Center of Virology and Biotechnology, Vector, Koltsovo 630559, Novosibirsk region, Russia., Prudnikova TY; Institute of Molecular Biology and Biophysics, 630117 Novosibirsk, Russia., Domanitskaya NV; Institute of Molecular Biology and Biophysics, 630117 Novosibirsk, Russia., Litviakov NV; Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia; National Research Tomsk State University, 634050 Tomsk, Russia., Maksimov VN; Institutе of Internal and Preventive Medicine, Branch of ICIG SB RAS, 630089 Novosibirsk, Russia., Cherdyntseva NV; Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia; National Research Tomsk State University, 634050 Tomsk, Russia., Grigorieva EV; Institute of Molecular Biology and Biophysics, 630117 Novosibirsk, Russia. Electronic address: elvira.grigorieva@niimbb.ru.
Jazyk: angličtina
Zdroj: Gene [Gene] 2017 Sep 10; Vol. 628, pp. 224-229. Date of Electronic Publication: 2017 Jul 20.
DOI: 10.1016/j.gene.2017.07.054
Abstrakt: d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A>G) were similar in healthy Siberian women (n=136) and cancer patients (n=129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR=1.76; 95% CI=1.04-1.90; P(Y)=0.035 χ 2 =4.44). Heterozygous AG genotype was associated with tumour size (OR=3.67, P(Y)=0.004), ER-negative tumours (OR=3.25, P(Y)=0.0028), triple-negative tumours (OR=4.94, P(Y)=0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER+PR+ luminal A breast cancer (OR=0.25, P(Y)=0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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