Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer

The present study was aimed to investigate the possible association between 19-base pair (bp) deletion polymorphism of the DHFR gene (rs70991108), null genotype of UDP-glucuronosyltransferase 2B17 (UGT2B17) as well as the expression level of nasopharyngeal carcinoma-associated gene 6 (NGX6) with the...

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Published in:	Molecular biology reports Vol. 39; no. 12; pp. 10531 - 10539
Main Authors:	Eskandari-Nasab, Ebrahim, Hashemi, Mohammad, Rezaei, Hamzeh, Fazaeli, Aliakbar, Mashhadi, Mohammad Ali, Moghaddam, Simin Sargholzaei, Arbabi, Farshid, Jahantigh, Mahdi, Taheri, Mohsen
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-12-2012 Springer Nature B.V
Subjects:	Alleles Animal Anatomy Animal Biochemistry Biomedical and Life Sciences Breast cancer Breast carcinoma Breast Neoplasms - enzymology Breast Neoplasms - genetics Data processing Dihydrofolate reductase Enzymes Female Gene Deletion Gene expression Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Gene polymorphism Genotype Genotype & phenotype Genotyping Glucuronosyltransferase - genetics Glucuronosyltransferase - metabolism Histology Humans Life Sciences Membrane Proteins - genetics Membrane Proteins - metabolism Middle Aged Minor Histocompatibility Antigens Molecular biology Morphology Polymerase Chain Reaction Ribonucleic acid Risk factors RNA RNA, Messenger - genetics RNA-directed DNA polymerase Statistical analysis Tetrahydrofolate Dehydrogenase - genetics Tetrahydrofolate Dehydrogenase - metabolism Tumor suppressor genes Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumors UDP-glucuronosyltransferase DHFR UGT2B17 Breast cancer NGX6 expression Gene deletion
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Summary:	The present study was aimed to investigate the possible association between 19-base pair (bp) deletion polymorphism of the DHFR gene (rs70991108), null genotype of UDP-glucuronosyltransferase 2B17 (UGT2B17) as well as the expression level of nasopharyngeal carcinoma-associated gene 6 (NGX6) with the risk of breast cancer. This case–control study was done on 236 patients with breast cancer and 203 cancer free women. Detection of 19-bp del of DHFR was done using bi-directional PCR allele-specific amplification and UGT2B17 genotyping was performed using multiplex PCR assay. NGX6 mRNA expression level was determined by quantitative reverse transcriptase PCR in 62 breast cancerous and 62 adjacent non-cancerous tissues. Our finding showed an association between null genotype of UGT2B17 and risk of breast cancer and the null genotype increased susceptibility to breast cancer (OR: 2.99; 95 % CI: 1.94–4.60; p < 0.0001). However, no statistically significant difference was found between breast cancer patients and cancer free normal women regarding 19-bp ins/del of DHFR (χ 2 = 0.91, p = 0.63). Real-time PCR data showed that the relative expression level of NGX6 mRNA was significantly lower in cancerous than that in non-cancerous breast tissue specimens (0.936 ± 0.042 and 1.042 ± 0.039, respectively). However, NGX6 mRNA expression was not correlated with tumors grade ( p > 0.05). In conclusion, the null genotype of UGT2B17 revealed to be a risk factor for breast cancer in a sample of Iranian population. Furthermore, down-regulation of NGX6 mRNA expression in breast carcinoma confirms the growing proof regarding the tumor suppressor role of NGX6.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0301-4851 1573-4978
DOI:	10.1007/s11033-012-1938-8