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 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.
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Ebrahim
E
Eskandari-Nasab
Mohammad
M
Hashemi
Hamzeh
H
Rezaei
Aliakbar
A
Fazaeli
Mohammad Ali
MA
Mashhadi
Simin Sargholzaei
SS
Moghaddam
Farshid
F
Arbabi
Mahdi
M
Jahantigh
Mohsen
M
Taheri
D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; C477325:TMEM8B protein, human; D025521:Tumor Suppressor Proteins; D013762:Tetrahydrofolate Dehydrogenase; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human