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Association between Cyclin D1 G870A (rs9344) polymorphism and cancer risk in Indian population: meta-analysis and trial sequential analysis.

ABSTRACT: Introduction: Association between Cyclin D1 (CCND1) single nucleotide polymorphism (SNP) rs9344 and cancer risk is paradoxical. Thus, we performed a meta-analysis to explore the association between CCND1 variant and overall cancer risk in Indian population. Methods: Data from 12 published studies including 3739 subjects were collected using Pubmed and Embase. RevMan (Review Manager) 5.3 was used to perform the meta-analysis. OR with 95%CI were calculated to establish the association. Results: Overall, the cumulative findings demonstrated that CCND1 polymorphism (rs9344) was not significantly associated with cancer risk in all the genetic models studied (dominant model: GG vs GA+AA: OR (95%CI) = 0.81 (0.60-1.09), P=0.17; recessive model: GG+GA vs AA: OR (95%CI) = 1.23 (0.96-1.59), P=0.11; co-dominant model: GG vs AA: OR (95%CI) = 1.35 (0.93-1.97), P=0.12; co-dominant model: (GG vs GA: OR (95%CI) = 1.16 (0.85-1.59), P=0.34; allelic model: A vs G: OR (95%CI) = 1.20 (1.14-2.85), P=0.23; allelic model: G vs A: OR (95%CI) = 0.83 (0.62-1.12), P=0.23). Subgroup analysis according to cancer types presented significant association of CCND1 polymorphism and increased breast cancer risk in dominant model (GG vs GA+AA: OR = 2.75, 95%CI = 1.54-4.90, P=0.0006) and allelic model (G vs A: OR = 1.63, 95%CI = 1.22-2.19, P=0.001). An increased esophageal cancer risk in recessive model (GG+GA vs AA: OR = 1.51, 95%CI = 1.05-2.16, P=0.03) and co-dominant model (GG vs AA: OR = 2.51, 95%CI = 1.10-5.71, P=0.03) was detected. A higher risk for colorectal cancer was detected under both the co-dominant models (GG vs AA: OR = 2.46, 95%CI = 1.34-4.51, P=0.004 and GG vs GA: OR = 1.74, 95%CI = 1.14-2.67, P=0.01). However, in case of cervical cancer risk a non-significant association was reported under the recessive model (GG+GA vs AA: OR = 1.52, 95%CI = 0.60-3.90, P=0.38) with reference to CCND1 polymorphism (rs9344). The trial sequential analysis (TSA) showed that the cumulative Z-curve neither crossed the trial sequential monitoring boundary nor reached the required information size (RIS). Thus, present meta-analysis remained inconclusive due to insufficient evidence. Conclusion: CCND1 polymorphism rs9344 may not have a role in overall cancer susceptibility in Indian population. However, this polymorphism acts as a crucial risk factor for breast, esophageal, and colorectal cancer but not for cervical cancer. Future studies with larger sample size are required to draw a reliable conclusion.

SUBMITTER: Thakur N

PROVIDER: S-EPMC6265616 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association between Cyclin D1 G870A (rs9344) polymorphism and cancer risk in Indian population: meta-analysis and trial sequential analysis.

Thakur Nisha N Kumari Suchitra S Mehrotra Ravi R

Bioscience reports 20181130 6

Introduction: Association between Cyclin D1 (CCND1) single nucleotide polymorphism (SNP) rs9344 and cancer risk is paradoxical. Thus, we performed a meta-analysis to explore the association between CCND1 variant and overall cancer risk in Indian population. Methods: Data from 12 published studies including 3739 subjects were collected using Pubmed and Embase. RevMan (Review Manager) 5.3 was used to perform the meta-analysis. OR with 95%CI were calculated to est ...[more]

PMID: 30361291

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Project description:BackgroundCyclin D1 (CCND1) G870A polymorphism may be associated with hepatocellular carcinoma (HCC) risk, but the results of previous studies were inconsistent. Available evidence was meta-analyzed to assess their potential association.MethodsDatabases PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature database, China National Knowledge Infrastructure, and Google Scholar were systematically searched. Meta-analyses were performed to investigate the association of G870A polymorphism with HCC risk by calculating odds ratios (ORs) and 95% confidence intervals (CIs) from the data of relevant case-control studies.ResultsResults of this meta-analysis of six case-control studies involving 1,030 cases and 1,683 controls indicate that G870A polymorphism was not associated with HCC risk in any of the five genetic models tested (recessive model: AA vs GG + AG: OR =1.38, 95% CI =0.95-2.00, P=0.09; dominant model: AG + AA vs GG: OR =1.38, 95% CI =0.87-2.20, P=0.17; homozygous model: AA vs GG: OR =1.60, 95% CI =0.87-2.94, P=0.13; heterozygous model: AG vs GG: OR =1.24, 95% CI =0.86-1.79, P=0.25; allelic model: A vs G: OR =1.30, 95% CI =0.95-1.80, P=0.10). Subgroup analyses according to ethnicity showing marginally significant association between this single nucleotide polymorphism and HCC risk indicate that G870A may be significantly associated with HCC risk in Caucasian populations (recessive model: AA vs GG + AG: OR =2.34, 95% CI =1.60-3.42, P<0.0001; dominant model: AG + AA vs GG: OR =2.44, 95% CI =1.19-4.97, P=0.01; homozygous model: AA vs GG: OR =3.42, 95% CI =1.80-6.50, P=0.0002; allelic model: A vs G: OR =2.06, 95% CI =1.31-3.24, P=0.002), but not in Asian populations.ConclusionAvailable evidence suggests that no significant association between G870A polymorphism and HCC risk was found in either total populations or Asian populations. However, significant association was found in Caucasian populations. These results should be verified and extended in further detailed and well-designed studies involving larger, multiethnic samples.

Project description:PURPOSE:Several 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 METHODS:We 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. RESULTS:The 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). CONCLUSION:The 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.

Dataset Information

Association between Cyclin D1 G870A (rs9344) polymorphism and cancer risk in Indian population: meta-analysis and trial sequential analysis.

Publications

Association between <i>Cyclin D1</i> G870A (rs9344) polymorphism and cancer risk in Indian population: meta-analysis and trial sequential analysis.

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