CCND1 G870A Polymorphism Research Articles

Cyclin D1 (G870A) polymorphism and breast cancer risk in an Iranian population

Background and Objective: Cyclins are the key regulator of the cell cycle and their over-expression has been seen in many cancers including breast cancer. Cyclin D1 is an oncoprotein encoded by CCND1 gene located on chromosome 11 (11q) which regulates cell cycle in shifting from G1 to S phase. It’s the main target for steroids and mitogenic growth hormones in breast epithelial cells. This study aimed to evaluate the relationship between Cyclin D1 G870A polymorphism and breast cancer risk in a population in the north of Iran.
 Methods: Whole blood samples collected from 82 patients with breast cancer and 66 healthy women. DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique.
 Results: Genotypic prevalence of AA, AG, GG genotypes among patients were 40.2%, 35.3% and 24.4% and in controls were 30%, 47%, 23%, respectively. There was no significant difference in CCND1 G870A genotype polymorphism between patients and control group (p=0.32). Also, allelic prevalence of A and G alleles in breast cancer patients were 58% and 42%, in controls were 54% and 46%, respectively. The present study showed that there is no significant association between CCND1 G870A polymorphism with the risk of breast cancer.
 Conclusion: The results of this study revealed that there is no significant association between CCND1 G870A genetic polymorphism and the risk of breast cancer in the population of the north of Iran. More studies with larger samples of cases and controls would be beneficial.

Influence of cyclin D1 splicing variants expression on breast cancer chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.

Cyclin D1 (CCND1), a mediator of cell cycle control, has a G870A polymorphism which results in the formation of two splicing variants: full-length CCND1 (CCND1a) and C-terminally truncated CCND1 species (CCND1b). However, the role of CCND1a and CCND1b variants in cancer chemoresistance remains unknown. Therefore, this study aimed to explore the molecular mechanism of alternative splicing of CCND1 in breast cancer (BC) chemoresistance. To address the contribution of G870A polymorphism to the production of CCND1 variants in BC chemoresistance, we sequenced the G870A polymorphism and analysed the expressions of CCND1a and CCND1b in MCF-7 and MCF-7/ADM cells. In comparison with MCF-7 cells, MCF-7/ADM cells with the A allele could enhance alternative splicing with the increase of SC-35, upregulate the ratio of CCND1b/a at both mRNA and protein levels, and activate the CDK4/CyclinD1-pRB-E2F1 pathway. Furthermore, CCND1b expression and the downstream signalling pathway were analysed through Western blotting and cell cycle in MCF-7/ADM cells with knockdown of CCND1b. Knockdown of CCND1b downregulated the ratio of CCND1b/a, demoted cell proliferation, decelerated cell cycle progression, inhibited the CDK4/CyclinD1-pRB-E2F1 pathway and thereby decreased the chemoresistance of MCF-7/ADM cells. Finally, CCND1 G870A polymorphism, the alternative splicing of CCDN1 was detected through Sequenom Mass ARRAY platform, Sanger sequencing, semi-quantitative RT-PCR, Western blotting and immunohistochemistry in clinical BC specimens. The increase of the ratio of CCND1b/a caused by G870A polymorphism was involved in BC chemoresistance. Thus, these findings revealed that CCND1b/a ratio caused by the polymorphism is involved in BC chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.

Cell Cycle Regulatory CCND1 G870A Gene Polymorphism and Periodontitis-Induced Oral Cancer: A Risk Analysis

Abstract Strong association has been recently observed between periodontitis/gingivitis and Oral squamous cell carcinoma (OSCC). A high incidence of oral cancer has been reported in the case of chronic periodontitis. Recently Cell cycle regulatory /Senescence genes have been associated with Gingivitis/ Periodontitis susceptibility. Cyclin D1 is one such cell cycle regulatory gene. Several findings have reported that Cyclin D1 (CCND1) G870A Single nucleotide polymorphism is associated with oral cancer (OC) risk, but yielded inconsistent data across different studies. This meta-analysis explores the precise relationship between CCND1 G870A polymorphism and OC risk. PubMed (Medline), EMBASE, & Google Scholar databases were searched for eligible studies and pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated. Newcastle-Ottawa analysis was done for selected articles quality assessment, bias in publication (if any) was estimated through Funnel plots and Egger’s test. Pooled analysis from eleven eligible studies suggests that CCND1 G870A polymorphism is not significantly associated with OC risk. Sub-group analysis by ethnicity failed to show any association. Sequential single study omission was performed to determine the credibility and resilience of the inferences drawn.

Cyclin D1 G870A Polymorphism: Relation to the Risk of ALL Development, Prognosis Impact, and Methotrexate Cytotoxicity.

Background:Cyclin D1 (CCND1) regulates cell cycle progression during the late G1 and S phase and takes part in methotrexate metabolism. It was hypothesized that CCND1 gene polymorphism affects acute lymphoblastic leukemia (ALL) development, prognosis and may relate to methotrexate cytotoxicity. Subjects and methods:This study included 50 ALL patients and 50 healthy controls, CCND1 G870A polymorphism was studied in all items using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and evaluated methotrexate cytotoxicity for ALL patients using liver function tests before and after methotrexate treatment. We followed up patients for one year to determine disease-free survival (DFS) and overall survival (OS) and its relation to the CCND1 genotype. Results:We found that AA genotype and A allele have a higher risk of developing ALL compared to the control group. Additionally, we found no notable association between CCND1 variant and methotrexate cytotoxicity and no role of CCND1 polymorphism in ALL prognosis. Conclusion:Our results suggested that CCND1 G870A polymorphism is associated with a high risk of ALL development. However, it has no role in ALL prognosis or methotrexate cytotoxicity.

Association of CCND1 rs603965 Polymorphism with Breast Cancer Risk in North Indian Population

The potential association of G870A SNP (rs603965) of cyclin D1 gene (CCND1) with susceptibility to breast cancer in the north Indian population was investigated. The study included 230 subjects comprising 115 breast cancer cases and an even number of controls. PCR-RFLP employed for genotyping revealed that the females carrying AA genotype have 2.66- fold increased risk for development of breast cancer in the total cohort (OR 2.66, 95% CI 1.25– 5.67; P= 0.017) compared to GG genotype. Further, a significantly higher risk was also observed in premenopausal women (OR 3.35, 95% CI 1.22– 9.18; P= 0.0310). However, GG and GA genotype are not found associated significantly with breast cancer risk. The results suggest that CCND1 G870A polymorphism influences the genetic susceptibility to breast cancer. Larger studies conducted in diverse populations are needed to ascertain the contribution of these risk alleles to breast cancer risk.

The Association between Cyclin D1 (CCND1) rs9344 AA Genotype and Increased Risk of Colorectal Cancer in An Iranian Population

Background: Colorectal cancer (CRC) is a globally growing disease with a steady decrease in the age of incidence. Pathogenesis of this cancer stems from a complex interaction between environmental factors and genetic predisposition. Among genetic factors, high activity of cyclin D1gene is prominent. A polymorphism (G870A) in exon 4 of cyclin D1 is responsible for a variant transcript with longer half-life and may culminate in uncontrollable cellular growth, thereby contributing to cancer development. Method: This case-control study evaluated the frequency of CCND1 G870A polymorphism and risk of sporadic CRC in an Iranian population. The study population comprised 50 CRC patients and 50 CRC-free controls selected on the basis of colonoscopy examination. For genotyping, we performed polymerase chain reaction – restriction fragment length polymorphism analysis (PCR-RFLP). Result: AA genotype frequencies compared to GA+GG genotype frequencies between cases and controls showed that AA genotype frequency in the case group was significantly higher than the control group (AA vs. GG + GA: OR= 2.25, 95% CI: 1.13-5.54, P=0.04). Allele A frequency was 57% in patients and 46% in healthy subjects. Statistical analysis showed that the odds ratio of carriers with allele A for risk of CRC was 1.55 more than G allele carriers (OR=1.55, 95% CI: 0.856-2.828). Moreover, physical activity in cases was significantly less than controls (P=0.001). We further observed that the subjects in the case group used fewer non-steroidal antiinflammatory drugs compared to healthy controls (P=0.02). Analysis of body mass index (BMI) between cases and controls revealed that the average of BMI in cases was higher than the controls (P =0.04). Conclusion: Our results showed that individuals carrying the AA genotype ran a higher risk of developing CRC compared to GG genotype.

AA genotype of cyclin D1 G870A polymorphism increases breast cancer risk: Findings of a case-control study and meta-analysis.

Cyclin D1 (CCND1) polymorphisms, a regulator of the cell cycle progress from G1 to the S phase, may lead to uncontrolled cell proliferation and lack of apoptosis. G870A, a common single-nucleotide polymorphism in CCND1 influences breast cancer risk. However, the association between G870A polymorphism and breast cancer risk is ambiguous so far. In this case-control study, we analyzed the role of G870A polymorphism with breast cancer risk in Indian women. A meta-analysis of 18 studies was also performed to elucidate this association by increasing statistical power. In our case-control study, significant risk association of the CCND1 G870A AA genotype with breast cancer in total cohort (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64-5.42; P value, 4.96e-04) and premenopausal women (OR, 3.31; 95% CI, 1.54-7.08; P value, .003) was found. The results of the meta-analysis showed that AA genotype of the CCND1 G870A polymorphism significantly increases breast cancer risk in total pooled data (AA vs GG+GA: OR = 1.20; 95% CI = 1.03 to 1.39; P value, 0.016*) and Caucasian (AA vs GG+GA: OR = 1.22; 95% CI = 0.99 to 1.51; P value, .056*) but not in Asian population. Further, a significant protective association with breast cancer was also found in the GA vs AA comparison model in pooled data (OR = 0.73; 95% CI = 0.58 to 0.92; P value, .007*) as well as in Caucasian subgroup (OR = 0.62; 95% CI = 0.49 to 0.94; P value, .022*). CCND1 G870A AA genotype was found associated with breast cancer risk. Future association studies considering the environmental impact on gene expression are required to validate/explore this association.

Association of the cyclin D1 G870A polymorphism with risk of multiple myeloma in a group of Egyptian patients

Background Multiple myeloma (MM) is a clonal bone marrow disease characterized by the neoplastic transformation of mature B cells. Single-nucleotide polymorphisms in the Cyclin d1 CCND1 gene were reported with an increased susceptibility to various human cancers such as breast cancer, bladder cancer, colorectal cancer, and lung cancer. Aim The aim of this study was to detect the distribution of CCND1 G870A genotypes in a group of MM patients and in controls in an attempt to reveal the possible association between the presence of the polymorphism (G870A) and the risk of MM in an Egyptian population. Patients and methods The PCR-restriction fragment length polymorphism technique was used for the detection of CCND1 G870A polymorphism in 56 MM patients and 70 healthy individuals as a control group. Results The homozygous GG genotype was present in 10.7% of patients, heterozygous AG in 48.2%, and homozygous AA in 41.1%. Carriers of CCND1 G870A polymorphism did not show increased risk to MM [AG genotype odds ratio (OR)=0.928, P=0.899 and GG genotype OR=1.295, P=0.499]. Patients aged at least 60 years had a higher frequency of mutant CCND1 than controls (88.2 and 64.3%), but this difference did not reach statistical significance (OR=4.167, P=0.128). Conclusion Carriers of the pleomorphic genotype of CCND1 G870A did not show increased susceptibility to MM. Larger population-based studies are needed to validate the association of CCND1 G870A polymorphism with MM.

The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis: Erattum.

The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis: Erattum.

The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis.

Background:CyclinD1 (CCND1) is a key cell cycle regulatory protein. A large number of epidemiological studies have assessed the potential correlation between the CCND1 G870A polymorphism and the risk of colorectal cancer (CRC), but their findings have been inconsistent. To obtain a more precise understanding of the association between the G870A polymorphism in the CCND1 gene and the CRC risk, we conducted a more comprehensive meta-analysis.Methodology:We searched PubMed, Ovid, Springer, Weipu, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering all publications (the last search was updated on January 10, 2017). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. Statistical analyses were performed using Review Manager 5.3 and STATA 10.0 software.Results:A total of 7276 CRC patients and 9667 controls from 27 publications were included in this meta-analysis. We found that compared with GG homozygote genetic model, AA, AG, AA + AG genetic models of the CCND1 G870A polymorphism were significantly associated with overall CRC risk (AA homozygote genetic model: OR = 1.28, 95% CI = 1.10–1.49; AG heterozygote genetic model: OR = 1.15, 95% CI = 1.06–1.25; AA homozygote + AG heterozygote genetic model: OR = 1.19, 95% CI = 1.07–1.33). Subgroup analyses by ethnicity and cancer location showed that A carriers were consistently associated with a significantly increased risk of CRC in all subsets of participants (Asian and Caucasian; colon cancer and rectal cancer). When stratified by study design, we found a significant association in hospital-based studies (HB), but no significant associations were found in either population-based studies (PB) or family-based studies (FB). According to subgroup analysis by cancer type, the risk of sporadic colorectal cancer (sCRC) and hereditary nonpolyposis colorectal cancer (HNPCC) were not correlated with the CCND1 G870A polymorphism, except AG (AG vs GG: OR = 1.30, 95% CI = 1.11–1.53).Conclusions:This meta-analysis suggests that the CCND1 G870A polymorphism is associated with an increased risk of CRC, especially that A carriers may be a major risk factor for CRC.

Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis.

Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women. Cyclin D1 (CCND1) is a cell cycle regulatory protein that is required for the G1 phase, and increased expression levels of this protein may affect tumorigenesis. The present study aimed to assess the possible effect of the CCND1 G870A polymorphism on UL susceptibility. A total of 154 women with UL and 197 healthy women who were age-, body mass index (BMI)- and ethnicity-matched were genotyped for the CCND1 G870A (rs9344) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The effects of G870A transition on the structure of mRNA and proteins of CCND1 was evaluated using bioinformatics tools. The frequency of the CCND1 870AA genotype was significantly higher in women with UL compared with the control subjects, and the risk of UL was 1.4-fold higher in women with the AA genotype when compared with the GG genotype before and after adjusting for age, BMI, and ethnicity [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-2 (P=0.02)]. The frequency of CCND1 870GA genotype was not significantly different between the two groups. The frequency of the CCND1 870A allele was significantly higher in the women with UL when compared with the control subjects (57 vs. 48%; P=0.02). The in silico analysis revealed that the G870A transition may fundamentally alter the structure of the CCND1-mRNA. Thus, the CCND1 870AA genotype was associated with UL susceptibility in a sample of women from the southeast of Iran.

Association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer risk: a meta-analysis.

Published data on the association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between CCND1 G870A polymorphism and GC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to June 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Nine studies published from 2003 to 2014, with a total of 1813 cases and 2173 controls, were included in this meta-analysis. The pooled results showed that there was no association between CCND1 G870A polymorphism and GC risk in any genetic model. The subgroup analysis stratified by ethnicity showed an increased breast cancer risk in Caucasian based on heterozygote comparison (GA vs. GG: OR=1.49, 95% CI=1.06-2.10, P=0.02). We found the same association in population based (PB) stratified analyses by Source of controls (AA vs. GG: OR=1.39, 95% CI=1.01-1.93, 0.05). When stratifying by the type, Sex and H. pylori infection in dominant model, Interestingly, we found the opposite result in Male (AA + GA vs. GG: OR=0.5, 95% CI=0.33-0.76, P=0.001), there were no association between CCND1 G870A polymorphism and GC risk in any other subgroup. This meta-analysis suggests that CCND1 G870A polymorphism is a risk factor for susceptibility to GC in Caucasians and in general populations. While, CCND1 G870A polymorphism plays a possible protective effect in GC in Male. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Association between the Cyclin D1 G870A polymorphism and the susceptibility to and prognosis of upper aerodigestive tract squamous cell carcinomas: an updated meta-analysis.

PurposeSeveral publications have investigated the association between the Cyclin D1 G to A substitution at nucleotide 870 (CCND1 G870A) polymorphism and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), but their conclusions still remain controversial. We conducted a meta-analysis to precisely evaluate this association.Patients and methodsWe electronically searched the Chinese National Knowledge Infrastructure, PubMed, and Embase (up to January 2015) databases for case–control studies on the association between the CCND1 G870A polymorphism and SCC of the UADT, and 23 studies were included in total.ResultsThe meta-analysis results showed that there was a significant association between the CCND1 G870A polymorphism and the risk of SCC of the UADT (AA vs GG: odds ratio [OR] =1.33, 95% confidence interval [CI] =1.01–1.74, P<0.001 for heterogeneity; GA/AA vs GG: OR =1.24, 95% CI =1.01–1.51, P<0.001 for heterogeneity; AA vs GA/GG: OR =1.16, 95% CI =0.97–1.39, P<0.001 for heterogeneity; allele A vs allele G: OR =1.14, 95% CI =1.00–1.30, P<0.001 for heterogeneity; GA vs GG: OR =1.18, 95% CI =0.98–1.42, P<0.001 for heterogeneity). However, when analyzing prognosis, allele G was a potential risk factor for poor tumor differentiation (AA vs GA/GG: OR =2.60, 95% CI =1.15–5.86, P=0.836 for heterogeneity) and reduced disease-free intervals (OR =2.08, 95% CI =1.17–3.69, P=0.134 for heterogeneity). In the subgroup analysis, the cancer susceptibility of Asian groups, population-based control groups, nasopharyngeal cancer groups, and esophageal SCC groups were more likely to be affected by the CCND1 G870A polymorphism. No significant publication bias was found in our analysis (P=0.961 for Egger’s test and P=0.245 for Begg’s test).ConclusionThe results of the present meta-analysis suggest that the variant CCND1 870A allele might confer an elevated risk of SCC of the UADT, particularly among Asians and individuals who have esophageal or nasopharyngeal cancers. Moreover, the CCND1 870A allele might also confer better tumor differentiation grades and longer disease-free intervals.

Note of the methodological flaws in the paper entitled "Association between the G870A polymorphism of cyclin D1 gene and glioma risk".

Dear Editor, Recently, we had the honor of reading a meta-analysis article published in Tumor Biology which was completed by the investigators (Zong et al.) [1]. Because of our interest in the association between the G870A polymorphism of cyclin D1 gene and glioma risk, we carefully read the entire article. In this study, the investigators performed a meta-analysis of four independent studies to examine whether CCND1 G870A polymorphism was associated with glioma risk. A significant association was found between the CCND1 G870A polymorphism and glioma risk in three genetic models (ORA vs. G= 1.178, 95 % CI 1.025–1.354, POR=0.021; ORAA vs. GG= 1.328, 95 % CI 1.007–1.750, POR=0.045; ORAA+AG vs. GG= 1.253, 95 % CI 1.006–1.516, POR=0.044). They finally reached an important conclusion that the CCND1 G870A polymorphism is a risk factor for the development of glioma. It is a valuable study on the association of CCND1 G870A polymorphism with glioma risk. Nevertheless, there are several deficiencies in the methodology we would like to raise related to this article. To begin with, only four electronic databases, namely, PubMed, Embase, Web of Science, and Wanfang databases for articles up to October 31, 2013 were searched for the meta-analysis. The small number of required papers would be an important limitation of the meta-analysis. We recommended that more electronic databases (such as OVID, SCOPUS, Science Citation Index, Cochrane-controlled Trials Register, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) should be searched. Meanwhile, the investigators just showed us some search terms such as glioma, brain tumor, polymorphism, variant, CCND1, cyclin D1, and rs603965. To make the meta-analysis more credible, the investigators should provide us the flow chart of literature search and the detailed manual search strategy. Furthermore, the investigators did not evaluate the quality of the four included studies. As is well known, articles of high quality are requirements for a convincing meta-analysis. Introduction of much low-quality articles may result in wrong conclusions. To make the meta-analysis more credible, the investigators should perform the quality evaluation by using some authority standards, such as the Newcastle-Ottawa Scale (NOS) [2] and Downs-Black tool [3]. Finally, there was significant heterogeneity in the recessive genetic model in Caucasians (AA vs. AG+GG, I=74.6 %, PH=0.047). However, the investigators did not find out the source of heterogeneity. We recommend that the investigators should perform a one-way sensitivity analysis [4, 5] to find out the source of heterogeneity. In conclusion, thanks go to the investigators for their contribution to supplying us with an assessment of the relationship between CCND1G870A polymorphism and glioma risk. However, considering the above methodological flaws in the meta-analysis, we hope that the investigators would redo the meta-analysis with the correct method and to reconsider the conclusions based on the new results. * Sen-ren Guo fjtcmsenren@163.com

Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population

The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The “A” allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. Herein, the tumor relevance of G870A polymorphism, the association between cyclin D1 variant expression and G870A genotype, and the oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma (HCC) were examined. We found that there is no significant difference of G870A distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and healthy control groups. Stratification analysis revealed that in younger patients (ages ≤ 50), cirrhotic CHB patients with AA genotype had an increased risk of developing HCC with odds ratio of 1.943 (95 % CI 1.022–3.694, p = 0.0411) as compared with AG/GG genotypes. The two variants were both transcripted from “A” and “G” alleles, and neither cyclin D1a nor D1b production was influenced by G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC. Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-015-3401-7) contains supplementary material, which is available to authorized users.

Effect of the CCND1 A870G polymorphism on prostate cancer risk: a meta-analysis of 3,820 cases and 3,825 controls.

BackgroundCyclin D1 (CCND1) is critical in the transition of the cell cycle from the G1 to S phases, and unbalanced cell cycle regulation is a hallmark of carcinogenesis. Numerous epidemiological studies have evaluated the association between the CCND1 A870G polymorphism and the risk of prostate cancer (PCa). However, these studies have yielded conflicting results.MethodsIn the present study, the possible association above was assessed by a meta-analysis. Eligible articles were identified for the period up to July 2014. Pooled odds ratios (ORs) with 95% confidence intervals (95% CI) were appropriately derived from fixed effects or random effects models.ResultsA total of ten case-control studies, which included 3,820 cases and 3,825 controls, were identified. Overall, the allelic/genotypic association between the G870A polymorphism and prostate cancer was nonsignificant (OR = 1.045, 95% CI = 0.947 to 1.153 for A versus G, P = 0.380; OR = 1.088, 95% CI = 0.896 to 1.321 for AA versus GG, P = 0.393; OR = 1.044, 95% CI = 0.941 to 1.158 for GA versus GG, P = 0.414; OR = 1.053, 95% CI = 0.955 to 1.161 for the dominant model AA + GA versus GG, P = 0.303; OR = 1.072, 95% CI = 0.881 to 1.306 for the recessive model AA versus AA + GA, P = 0.486). Moreover, subgroup analyses according to ethnicity failed to demonstrate a significant association between this polymorphism and prostate cancer. In addition, we also performed a stratified analysis of cases with PCa metastasis, and the results supported the findings of no significant association between CCND1 A870G polymorphism and metastasis risk of PCa.ConclusionsOur results suggest that the CCND1 A870G polymorphism might not be a potential candidate for predicting prostate cancer risk, including metastasis risk.

Cyclin D1 G870A gene polymorphism and risk of leukemia and hepatocellular carcinoma: a meta-analysis.

Cyclin D1 (CCND1) is a key protein involved in cell-cycle regulation, and the CCND1 G870A polymorphism is associated with many types of malignancy. Studies examining the associations between this G870A polymorphism and susceptibility to leukemia and hepatocellular carcinoma (HCC) have shown inconsistent results. Therefore, we conducted a meta-analysis to clarify these associations. A search of the PubMed database yielded 7 relevant articles: 3 pertaining to leukemia and 4 to HCC. The odds ratios (ORs) from individual studies were pooled using a fixed or random-effect model. A significant association was observed between the CCND1 G870A variant and leukemia under the allele contrast model [P = 0.003, OR = 1.49, 95% confidence interval (CI) = 1.15-1.95], the homozygote contrast model (P = 0.003, OR = 2.30, 95%CI = 1.34-3.96), and the recessive model (P = 0.002, OR = 2.03, 95%CI = 1.29-3.21). A significant association was observed between this variant and HCC under the recessive model (P = 0.0006, OR = 1.62, 95%CI = 1.23-2.14), the dominant model (P = 0.002, OR = 1.59, 95%CI = 1.19-2.14), the homozygote contrast model (P < 0.0001, OR = 2.06, 95%CI = 1.45-2.94), and the allele contrast model (P < 0.0001, OR = 1.43, 95%CI = 1.20-1.69). Our findings suggest that heritable CCND1 status may influence the risk of developing leukemia and HCC, and that more attention should be given to carriers of these susceptibility genes.

Cyclin D1 G870A polymorphism and risk of nasopharyngeal carcinoma: a case-control study and meta-analysis.

BackgroundCyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.MethodsWe firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.ResultsThe case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).ConclusionsA significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.

A cyclin D1 (CCND1) gene polymorphism contributes to susceptibility to papillary thyroid cancer in the Turkish population.

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotyping was determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects (45 ≤ years old) and female, in the Turkish population.

Association between cyclin D1 G870A polymorphism and cervical cancer risk: a cumulative meta-analysis involving 2,864 patients and 3,898 controls.

BackgroundAssociation between Cyclin D1 (CCND1) polymorphism and cervical cancer risk are conflicting with published articles. We performed a meta-analysis to investigate the association between CCND1 G870A polymorphism and cervical cancer risk.MethodsPubMed, Embase and CNKI data were researched to conduct a meta-analysis on the associations between CCND1 G870A polymorphism and cervical cancer risk. Ten published case–control studies including 2,864 patients with cervical cancer and 3,898 controls were collected in this meta-analysis. Odds ratio (OR) with 95% confidence interval (CI) were applied to assess the relationship; meta-regression, sensitivity analysis and cumulative analysis were also conducted to guarantee the strength of results.ResultsOverall, no significant association between CCND1 G870A polymorphism and cervical cancer risk were found in allele contrast (A vs. G: OR = 1.02, 95% CI = 0.88-1.19, P = 0.76 I2 = 74.5%), codominant model (GA vs. GG: OR = 0.98, 95% CI = 0.77-1.26, P = 0.90 I2 = 69.1%; AA vs GG: OR = 1.03, 95% CI = 0.75-1.41, P = 0.85 I2 = 75.9%), dominant model (GA + AA vs. GG: OR = 1.00, 95% CI = 0.78-1.28, P = 0.99 I2 = 72.3%) and recessive model (AA vs GG + GA: OR = 1.06, 95% CI = 0.85-1.23, P = 0.62, I2 = 70.1%). Similarly, in the stratified analysis by ethnicity, study design and genotyping type, no significant association detected in all genetic models either.ConclusionsOur meta-analysis indicated that CCND1 G870A might be not the crucial risk factor for the development of cervical cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_168