miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation
Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608...
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irk-123456789-1400892018-06-23T03:03:13Z miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation Hashemi, M. Sanaei, S. Rezaei, M. Bahari, G. Hashemi, S.M. Mashhadi, M.A. Taheri, M. Ghavami, S. Short communications Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Methods: This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53, 95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological characteristics of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings. 2016 Article miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation / M. Hashemi, S. Sanaei, M. Rezaei, G. Bahari, S.M. Hashemi, M.A. Mashhadi, M. Taheri,S. Ghavami // Experimental Oncology. — 2016 — Т. 38, № 1. — С. 57-59. — Бібліогр.: 31 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/140089 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Short communications Short communications |
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Short communications Short communications Hashemi, M. Sanaei, S. Rezaei, M. Bahari, G. Hashemi, S.M. Mashhadi, M.A. Taheri, M. Ghavami, S. miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation Experimental Oncology |
| description |
Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide
polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The
present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Methods:
This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR608
rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results:
Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval
(CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53,
95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological characteristics
of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased
risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings. |
| format |
Article |
| author |
Hashemi, M. Sanaei, S. Rezaei, M. Bahari, G. Hashemi, S.M. Mashhadi, M.A. Taheri, M. Ghavami, S. |
| author_facet |
Hashemi, M. Sanaei, S. Rezaei, M. Bahari, G. Hashemi, S.M. Mashhadi, M.A. Taheri, M. Ghavami, S. |
| author_sort |
Hashemi, M. |
| title |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation |
| title_short |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation |
| title_full |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation |
| title_fullStr |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation |
| title_full_unstemmed |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation |
| title_sort |
mir-608 rs4919510 c>g polymorphism decreased the risk of breast cancer in an iranian subpopulation |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2016 |
| topic_facet |
Short communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/140089 |
| citation_txt |
miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation / M. Hashemi, S. Sanaei, M. Rezaei, G. Bahari, S.M. Hashemi, M.A. Mashhadi, M. Taheri,S. Ghavami // Experimental Oncology. — 2016 — Т. 38, № 1. — С. 57-59. — Бібліогр.: 31 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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| first_indexed |
2025-07-10T09:45:33Z |
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2025-07-10T09:45:33Z |
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1837252726517399552 |
| fulltext |
Experimental Oncology 38, 57–59, 2016 (March) 57
miR-608 rs4919510 C>G POLYMORPHISM DECREASED THE RISK
OF BREAST CANCER IN AN IRANIAN SUBPOPULATION
M. Hashemi1,2,*, S. Sanaei2, M. Rezaei2, G. Bahari2, S.M. Hashemi3, M.A. Mashhadi3, M. Taheri4, S. Ghavami5
1Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan 98167–431758,
Iran
2Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences,
Zahedan 98167–431758, Iran
3Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences,
Zahedan 98167–431758, Iran
4Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences,
Zahedan 98167–431758, Iran
5Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences,
University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada
Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide
polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The
present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Me thods:
This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR-
608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results:
Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval
(CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53,
95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological charac-
teristics of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased
risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings.
Key Words: miR-608, breast cancer, polymorphism.
Breast cancer (BC) is one of the most prevalent types
of cancer in women. It is a major public and global health
problem and accounts for 14% of total cancer deaths
worldwide annually [1]. Similarly, BC is among the most
common malignancies amongst Iranian women [2]. Al-
though causes of BC are not yet completely understood,
genetic factors are indicated to play key roles in the
pathogenesis and progress of this malignancy [3–8].
MicroRNAs (miRNAs) are a highly conserved class
of small (~ 22 nucleotides), endogenous, non-coding
RNAs suppressing posttranscriptional gene expres-
sion by base pairing with their target messenger RNAs
(mRNAs) and inducing either translational repression
or mRNA degradation [9–11]. Loss of heterozygos-
ity in the 10q24 locus has been described in numeral
of human cancers [12–15]. Hsa-mir-608 lies within
an intron of SEMA4G in this region. Several single
nucleotide polymorphisms in the sequences of pre-
miRNAs such as miR-196a2 (rs11614913 T>C), miR–
499 (rs3746444 A>G), and miR-125a (rs12975333 G>T)
were associated with significantly increased risks
of BC in some but not all studies [7, 16–18].
It has been proposed that rs4919510 C>G variant
in miR-608 can alter its binding to target genes [19].
The expected targets of miR-608 include insulin recep-
tor (INSR), interleukin-1 alpha (IL1A), growth hormone
receptor (GHR), and TP53 [19].
Several studies examined the impact of miR-
608 rs4919510 C>G on the risk of various cancers,
but the results were inconsistent [20–26]. To the best
of our knowledge, limited studies evaluated associa-
tion between miR-608 rs4919510 polymorphism and
BC risk [21, 27, 28]. So, this case-control study was
designed to assess the possible association between
miR-608 rs4919510 polymorphism and susceptibility
to BC in an Iranian subpopulation.
MATERIALS AND METHODS
This case-control study was done on 160 BC patients
and 192 age-matched healthy women with no history
of cancer of any type (as the control group) in Zahe-
dan, southeast Iran. Ethical approvals for recruitment
were taken from local Ethics Committee of Zahedan
University of Medical Sciences, and informed consent
was obtained from all patients and healthy individu-
als. The study design and enrolment procedure were
described previously [29–31].
Genotyping of miR-608 rs4919510 C>G was done
by PCR–RFLP methods. Briefly, forward and reverse
primers were 5´-TCTGGCTAGGTAATGGCTCC-3´ and
5´-GCATCTGTGGCCTTCCATGA-3´, respectively. The
PCR product was digested by PvuII restriction en-
zyme (Fermentas). G allele digested and produced
242-bp and 117-bp pattern, while C allele undigested
and produced 359-bp fragment (Figure).
Submitted: January 07, 2016.
*Correspondence: E-mail: hashemim@zaums.ac.ir
Abbreviation used: BC — breast cancer; CI — confidence interval;
miRNAs — microRNAs; mRNAs — messenger RNAs; OR — odds ratio.
Exp Oncol 2016
38, 1, 57–59
58 Experimental Oncology 38, 57–59, 2016 (March)
M 1 2 3 4
100 bp —
200 bp —
300 bp —
400 bp —
500 bp —
Figure. Photograph of miR608 rs4919510 C>G polymorphism
using PCR-RFLP method. G allele digested by PvuII restriction
enzyme and produced 242-bp and 117-bp pattern, while C allele
was undigested (359-bp fragment). M — DNA marker; lanes
1 and 3 — CC; lane 2 and 4 — CG
Statistical analysis. Statistical analysis was done
using statistical package SPSS 20 software. The
categorical and continuous data were analyzed using
χ2 and t-test, respectively. The association between
genotypes and BC were assessed by computing the
odds ratio (OR) and 95% confidence intervals (CI) from
logistic regression analyses. A p-value of < 0.05 was
considered to be statistically significant.
RESULTS
The study group consisted of 160 BC patients with
an average age of 48.5 ± 10.8 years and 192 healthy
women with a mean age of 49.5 ± 12.4 years. No sig-
nificant difference was found between the groups
regarding age (p = 0.424).
The genotype and allele frequencies of miR-
608 rs4919510 C>G polymorphism in BC patients and
healthy women are shown. Our findings showed that
rs4919510 variant significantly decreased the risk of BC
(OR = 0.49, 95% CI 0.28–0.88, p = 0.018, CG vs CC)
(Table 1). Moreover, the G allele significantly decreased
the risk of BC (OR = 0.53, 95% CI 0.30–0.92, p = 0.024)
compared with C allele. No significant association was
found between miR-609 genotypes and clinicopatho-
logical characteristics of BC patients (p > 0.05).
Table 1. Association of miR-608 rs4919510 C>G polymorphism and risk
of BC
miR608
rs4919510 C>G Case, n (%) Control,
n (%) OR (95% CI) p
Genotype
CC 140 (87.5) 149 (77.6) 1.00 −
GC 20 (12.5) 43 (22.4) 0.49 (0.28–0.88) 0.018
GG 0 (0.0) 0 (0.0) − −
Allele
C 300 (93.8) 341 (88.8) 1.00 −
G 20 (6.2) 43 (11.2) 0.53 (0.30–0.92) 0.024
Hardy — Weinberg equilibrium (HWE) was as-
sessed by chi-square test. The genotype of miR-
608 rs4919510 polymorphism in both controls and
cases were in HWE (χ2 = 3.05, p = 0.081 and χ2 = 0.71,
p = 0.399, respectively).
As shown in Table 2, miR-608 rs4919510 polymor-
phism was not associated with clinicopathological
characteristics, including age, tumor size, tumor
stage, tumor grade, lymph node metastasis, estrogen
and progesterone receptors (ER, PgR) status, and
human epidermal growth factor receptor 2 (HER2/
neu) (p > 0.05).
Table 2. Association between miR-608 rs4919510 C>G variant and clini-
copathological characteristics of BC patients
Variables miR-608 rs4919510 pCC CG
Age 0.943
≤ 50 82 12
> 50 58 8
Tumor size, cm 0.467
≤ 2 49 9
> 2 86 11
Lymph node metastasis status 0.793
Yes 83 13
No 39 5
Grade 0.811
I 23 4
II 71 10
III + IV 19 4
Stage 0.994
I 24 3
II 55 8
III 39 6
IV 21 3
Histology 0.611
Ductal carcinoma 91 12
Others 43 8
ER 0.799
Positive 82 12
Negative 50 6
PgR 0.311
Positive 78 8
Negative 54 10
HER2/neu 0.244
Positive 74 7
Negative 65 12
DISCUSSION
In the present study we inspected the impact
of miR-608 rs4919510 variant on the risk of BC risk
in a sample of Iranian population. Our data showed that
rs4919510 polymorphism significantly decreased the risk
of BC in our population. We found no significant associa-
tion between miR-608 rs4919510 genotypes and clinico-
pathological characteristics of BC patients (p > 0.05).
Huang et al. [27] identified that the mir-
608 rs4919510 was not associated with BC risk, but
CG/GG genotypes were specifically associated with
increased risk of HER2-positive BC (OR = 1.97, 95%
CI 1.34–22.90). Variant G allele was the risk allele
with OR of 1.62 (95% CI 1.23–22.15). They found that
patients carrying GG-genotype also had larger HER2-
positive tumors. They concluded that rs4919510 poly-
morphism in mature miR-608 may influence HER2-
positive BC risk and proliferation of tumor. Jiao
et al. [21] have found no significant association between
miR-608 rs4919510 polymorphism and BC survival
in Chinese population. Dai et al. [28] observed that
miR-608 rs4919510 was not associated with BC risk.
Experimental Oncology 38, 57–59, 2016 (March) 59
In summary, our findings proposed that miR-
608 rs4919510 polymorphism decreased the risk
of BC in a sample of Iranian population. However,
we found no significant association between this
variant and the clinicopathological characteristics
of BC patients. Population based studies with larger
sample sizes with different ethnicities and long-term
follow-up are required to confirm our finding.
ACKNOwLEDGEMENT
This paper was funded by a research grant from the
Deputy for Research, Zahedan University of Medical
Sciences.
CONFLICTING INTERESTS
The Authors declare that there is no conflict of in-
terest to disclose.
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