Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 9  |  Page : 516-518

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population


1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China
2 Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China

Date of Web Publication29-Jun-2018

Correspondence Address:
Kai Jiang
Department of Hepatobiliary Surgery of Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing 100853,
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.203598

Rights and Permissions
 > Abstract 

Aims: Some studies investigated the association between CCND1 rs9344 polymorphism and hepatocellular carcinoma (HCC) risk. However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship.
Materials and Methods: Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases. The strength of the association was calculated with the odds ratio (OR) and respective 95% confidence intervals (Cis).
Results: We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88–1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05–2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71–1.18).
Conclusions: This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.

Keywords: CCND1, hepatocellular carcinoma, polymorphism


How to cite this article:
Wang Dd, Duan Wd, Zhu Zm, Tu Yl, Dou Cq, Han Mm, Zhang B, Zhao W, Jiang K. CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population. J Can Res Ther 2018;14, Suppl S2:516-8

How to cite this URL:
Wang Dd, Duan Wd, Zhu Zm, Tu Yl, Dou Cq, Han Mm, Zhang B, Zhao W, Jiang K. CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population. J Can Res Ther [serial online] 2018 [cited 2019 Jul 16];14:516-8. Available from: http://www.cancerjournal.net/text.asp?2018/14/9/516/235437


 > Introduction Top


Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. HCC is the fifth most commonly occurring solid tumor worldwide, with relatively high and increasing incidence as well as frequent relapse and dismal prognosis.[1]

CCND1 gene, located on chromosome 11q13, encodes the key cell cycle G1 regulatory protein CyclinD1, which promotes the phosphorylation of retinoblastoma protein and other substrates by binding to cyclin-dependent kinase 4/6 to make cells proliferation rapidly.[2] Overexpression of CCND1 is frequently observed in a variety of tumors including epithelial ovarian cancer, colorectal cancer, liver cancer, gastric cancer, nasopharyngeal carcinoma, and lung cancer resulting in altered cell cycle progression which contributes to tumorigenesis.[3]

Some studies investigated the association between CCND1 rs9344 polymorphism and HCC risk.[4],[5],[6],[7],[8],[9] However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship.


 > Materials and Methods Top


Publication search

Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases (the last retrieval date was March 22, 2016, using the search terms: “Cyclin D1 or CCND1” and “HCC”). All searched studies were retrieved and only published studies with full-text articles were included in the study. When more than publications with duplicate samples, only the newest study was used in this research.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) the diagnosis of HCC was confirmed by pathology; (2) the research was a case–control study or a cohort study; (3) the study focused on the association between CCND1 rs9344 polymorphism and HCC risk; and (4) the CCND1 rs9344 polymorphism of individual groups were provided. The exclusion criteria were as follows: (1) the HCC patients were not confirmed by pathology, (2) animal studies, and (3) reviews or abstracts.

Data extraction

The following data were recorded from each article:First author, years of publication, ethnicity of participants, numbers of cases and controls. The data were extracted by two of the authors independently. Discrepancies between these two authors were resolved by discussion.

Statistical analysis

The strength of association was assessed by calculating the odds ratio (OR) with 95% CI. The pooled ORs were performed for dominant model. Departure from Hardy–Weinberg equilibrium in controls was tested by the Chi-square test. A statistical test for heterogeneity was performed based on the Q-statistic. The P > 0.10 of the Q-test indicated a lack of heterogeneity among studies. Stratified analysis was performed by ethnicity. Potential publication bias was examined by Egger test. All statistical tests were performed with the software STATA version 11.0 (Stata Corporation, College station, TX, USA). A P < 0.05 was considered statistically significant.


 > Results Top


Literature search

Six studies met the inclusion criteria and were included in the final analysis. One study reported three case–control studies. Therefore, 1018 HCC patients and 1297 controls were included in the study. Four studies included Asian population; two studies were performed in Caucasians. The characteristics of included studies were summarized in [Table 1].
Table 1: Characteristics of the studies


Click here to view


Meta-analysis

We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88–1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05–2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71–1.18). No significant publication bias was found by Egger test (data not shown).


 > Discussion Top


This meta-analysis suggested that CCND1 rs9344 polymorphism was not significantly associated with HCC risk. Subgroup analyses based on ethnicity was conducted. CCND1 rs9344 polymorphism was associated with increased risk of HCC among Caucasians. However, no such result was found in Asians.

Fusté et al. suggested that the role of CCND1 in the cytoplasm is mainly associated with the invasive capability of tumor cells.[10] Yilmaz et al. indicated that downregulation of CCND1 expression may be an important mechanism by which everolimus increases the therapeutic window of paclitaxel in cervical cancers.[11] Li et al. found that loss expression of CCND1 might be an important event in the tumorigenesis in basal-like breast cancers.[12] Xu et al. reported that increased nuclear CCND1 is a potential unfavorable prognostic factor for lung adenocarcinoma patients, especially those with the clinical early stage.[13]

There were some limitations in this meta-analysis. First, lack of the original data limited the evaluation of gene-gene and gene-environment interactions. Second, we did not adjust other factors in this meta-analysis due to lack of the original data. Third, the studies included in our meta-analysis were small. Thus, our meta-analysis had little statistical power.


 > Conclusions Top


This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.

Financial support and sponsorship

This study is supported by Beijing Municipal Science and Technology Commission (No. Z151100003915155).

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011;365:1118-27.  Back to cited text no. 1
    
2.
Kenny FS, Hui R, Musgrove EA, Gee JM, Blamey RW, Nicholson RI, et al. Overexpression of cyclin D1 messenger RNA predicts for poor prognosis in estrogen receptor-positive breast cancer. Clin Cancer Res 1999;5:2069-76.  Back to cited text no. 2
    
3.
Huang XH, Jian WH, Wu ZF, Zhao J, Wang H, Li W, et al. Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation. Oncotarget 2014;5:5570-80.  Back to cited text no. 3
    
4.
Zhang YJ, Chen SY, Chen CJ, Santella RM. Polymorphisms in cyclin D1 gene and hepatocellular carcinoma. Mol Carcinog 2002;33:125-9.  Back to cited text no. 4
    
5.
Akkiz H, Bayram S, Bekar A, Akgöllü E, Ozdil B. Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study. Cancer Epidemiol 2010;34:298-302.  Back to cited text no. 5
    
6.
Hu Z, Zhou Z, Xiong G, Wang Y, Lai Y, Deng L, et al. Cyclin D1 G870A polymorphism and the risk of hepatocellular carcinoma in a Chinese population. Tumour Biol 2014;35:5607-12.  Back to cited text no. 6
    
7.
Pakakasama S, Chen TT, Frawley W, Muller CY, Douglass EC, Lee R, et al. CCND1 polymorphism and age of onset of hepatoblastoma. Oncogene 2004;23:4789-92.  Back to cited text no. 7
    
8.
Zeng Z, Tu J, Cheng J, Yao M, Wu Y, Huang X, et al. Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population. Tumour Biol 2015;36:6891-900.  Back to cited text no. 8
    
9.
Zhu ZZ. Correlation of cyclin D1 polymorphismwith genetic susceptibility to hepatocellular carcinoma. Chin J Cancer Prev Treat 2007;14:1521-3.  Back to cited text no. 9
    
10.
Fusté NP, Castelblanco E, Felip I, Santacana M, Fernández-Hernández R, Gatius S, et al. Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer. Oncotarget 2016. [Epub ahead of print].  Back to cited text no. 10
    
11.
Yilmaz A, Alp E, Onen HI, Menevse S. Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel. Contemp Oncol (Pozn) 2016;20:28-32.  Back to cited text no. 11
    
12.
Li Z, Cui J, Yu Q, Wu X, Pan A, Li L. Evaluation of CCND1 amplification and CyclinD1 expression: Diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers. Am J Transl Res 2016;8:142-53.  Back to cited text no. 12
    
13.
Xu P, Zhao M, Liu Z, Liu Y, Chen Y, Luo R, et al. Elevated nuclear CCND1 expression confers an unfavorable prognosis for early stage lung adenocarcinoma patients. Int J Clin Exp Pathol 2015;8:15887-94.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Materials and Me...>Results>Discussion>Conclusions>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed696    
    Printed9    
    Emailed0    
    PDF Downloaded33    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]