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

Abstract

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.

Keywords: CCND1 G870A polymorphism; predictive value; screen; squamous cell carcinoma.

Figure 1

Flowchart of screening studies.

Figure 2

Meta-analysis of the association between the CCND1 G870A polymorphism and tumor differentiation. Note: Diamonds represent pooled estimates, and the width of the diamonds represents 95% CIs of the summary point estimate of effect. Abbreviations: CCND1, Cyclin D₁; G870A, G to A substitution at nucleotide 870; CI, confidence interval; OR, odds ratio.

Figure 3

Meta-analysis of the association between the CCND1 G870A polymorphism and lymph node involvement. Notes: Diamonds represent pooled estimates, and the width of the diamonds represents the 95% CIs of the summary point estimate of the effect. Weights are from random effects analysis. Abbreviations: CCND1, Cyclin D₁; G870A, G to A substitution at nucleotide 870; CI, confidence interval; OR, odds ratio.

Figure 4

Meta-analysis of the association between the CCND1 G870A polymorphism and tumor size. Notes: Diamonds represent pooled estimates, and the width of the diamonds represents 95% CIs of the summary point estimate of the effect. Weights are from random effects analysis. Abbreviations: CCND1, Cyclin D₁; G870A, G to A substitution at nucleotide 870; CI, confidence interval; OR, odds ratio.

Figure 5

Meta-analysis of the association between the CCND1 G870A polymorphism and tumor recurrence. Note: Diamonds represent pooled estimates, and the width of the diamonds represents 95% CIs of the summary point estimate of the effect. Abbreviations: CCND1, Cyclin D₁; G870A, G to A substitution at nucleotide 870; CI, confidence interval; OR, odds ratio.

Figure 6

Meta-analysis of the association between the CCND1 G870A polymorphism and disease-free and survival intervals. Notes: Diamonds represent pooled estimates, and the width of the diamonds represents the 95% CIs of the summary point estimate of the effect. Weights are from random effects analysis. Abbreviations: CCND1, Cyclin D₁; G870A, G to A substitution at nucleotide 870; CI, confidence interval; HR, hazard ratio.

Figure 7

Funnel plot for the recessive model (AA vs GA/GG). Notes: Each point represents a separate study for the indicated association. The horizontal line indicates the effect size. Abbreviations: SE, standard error; log OR, natural logarithm of odds ratio.