Short Communication
Association of miR-502-binding site single nucleotide polymorphism in the
3
0
-untranslated region of SET8 and TP53 codon 72 polymorphism with
non-small cell lung cancer in Chinese population
Shaodi Yang
1
, Haiyan Guo
2
, Benjie Wei
1
, Shengcui Zhu
1
, Yanlin Cai
3
, Pei Jiang
1
*
, and Jianxin Tang
1
*
1
Key Laboratory of Green Packaging and Application of Biological Nanotechnology, Hunan University of Technology, Zhuzhou 412007, China
2
Department of Obstetrics and Gynecology, Xi’an No.4 Hospital, Xi’an 710004, China
3
First Hospital Affiliated to Nanhua University, Hengyang 421001, China
*Correspondence address. Tel/Fax: þ86-731-22182107; E-mail: 15886311258@163.com (J.T.)/Tel: þ86-731-22182106;
Fax: þ86-731-22182107; E-mail: jiangpei1106@163.com (P.J.)
The objective of this study was to identify whether the
miR-502-binding site single nucleotide polymorphism
(SNP) in the 3
0
-untranslated region (3
0
-UTR) of set
domain-containing protein 8 (SET8) and the tumor protein
p53 (TP53) codon 72 polymorphism were associated with
the risk for non-small cell lung cancer (NSCLC), either in-
dependently or jointly, among Chinese people from south-
ern Han. The genotypes of SET8 and TP53 codon 72
polymorphisms of peripheral blood DNA were detected
using polymerase chain reaction-restriction fragment
length polymorphism and direct DNA sequencing in a
case–control study on 164 NSCLC cases and 199 controls.
The SET8 TT (odds ratio, OR 5 2.173, 95% confidence
interval, CI 5 1.0454.517) or TP53 GG (OR 5 2.579, 95%
CI 5 1.366 – 4.870) genotype was associated with an
increased risk of NSCLC by compar ing with the SET8 CC
or TP53 CC genotype, respectively. Similar results were
obtained in SET8 recessive model (OR 5 2.074, 95% CI 5
1.019–4.221, P < 0.05), and the dominant and recessive
model of TP53 codon 72 were performed, respectively
(OR 5 1.809, 95% CI 5 1.159 – 2.825, P < 0.05; OR 5
1.933, 95% CI 5 1.096–3.409, P < 0.05). In addition, inter-
action between the SET8 and TP53 polymorphisms
increased the risk of NSCLC in a multiply manner, with
the OR being 3.032 (95%CI 5 1.580 – 5.816) for subjects
carrying both SET8 TT and TP53 GG genotypes.
Therefore, the miR-502-binding site SNP in the 3
0
-UTR of
SET8 and the TP53 codon 72 polymorphism may be
markers of genetic susceptibility to NSCLC in Chinese
population, and there is a possible gene –gene interaction
in the incidence of NSCLC.
Keywords SET8; tp53; polymorphism; non-small cell
lung cancer
Received: August 24, 2013 Accepted: November 1, 2013
Introduction
Lung cancer, predominantly, non-small cell lung cancer
(NSCLC) accounts for 19% of all malignant tumors. Lung
cancer has the highest mortality rate worldwide in recent
years [1 – 3]. Risk factors for lung cancer include smoking,
environment pollution, occupational factors, chronic lung
disease, and genetic factors. Identification of genetic variants
that are associated with lung cancer will contribute to the
understanding of underlying mechanisms behind its devel-
opment and potentially provide therapeutic targets.
Set domain-containing protein 8 (SET8), also known as
PR-SET7 or SETD8, is located on chromosome 12q24.31.
The histone H4 methyltransferase of SET8 gene is essential
to cell-cycle-dependent transcriptional silencing, the mitosis
of chromosome compaction in metazoans and the integrity
maintenance of genome [4 – 6]. The tumor protein p53
(TP53) gene is located on 17p13.1. The p53 protein is a key
tumor suppressor protein at the crossroads of cellular stress
response pathways, which can lead to cell-cycle arrest, DNA
repair, cellular senescence, differentiation, and apoptosis [7].
The histone methyltransferase SET8 methylates TP53 at
Lys-382, which is important to p53 function and the follow-
ing genome stability [8]. Mutation in either SET8 or TP53
may lead to loss of homeostatic control during human car-
cinogenesis.
Single nucleotide polymorphisms (SNPs) located in
microRNA-binding sites contribute to the disruption of
microRNA-target interactions and regulate the expression of
target gene [9–11]. One of the 129 variants of the SET8
gene polymorphisms (rs16917496, T!C) is located within
the miR-502-binding site in the 3
0
-untranslated region
Acta Biochim Biophys Sin 2014, 46: 149–154 | ª The Author 2013. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute
of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. DOI: 10.1093/abbs/gmt138.
Advance Access Publication 26 December 2013
Acta Biochim Biophys Sin (2014) | Volume 46 | Issue 2 | Page 149
by guest on March 4, 2014http://abbs.oxfordjournals.org/Downloaded from
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