Cyclin D1 G870A polymorphism contributes to colorectal cancer susceptibility: evidence from a systematic review of 22 case-control studies

Abstract

Background: Cyclin D1 (CCND1) plays a vital role in cancer cell cycle progression. Numerous epidemiological studies have evaluated the association between the CCND1 G870A polymorphism and the risk of colorectal cancer. However, these studies have yielded conflicting results. To derive a more precise estimation of this association, we conducted a meta-analysis and systematic review.

Methodology/principal findings: A comprehensive search was conducted to identify eligible studies of the CCND1 G870A polymorphism and colorectal cancer risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. We applied a grading system (Venice criteria) that assessed the epidemiological strength of the association. A total of 22 publications that included 6157 cases and 8198 controls were identified. We found that the CCND1 G870A polymorphism was significantly associated with overall colorectal cancer risk (homozygote genetic model: OR = 1.130, 95% CI = 1.023-1.248, P = 0.016; heterozygote genetic model: OR = 1.124, 95% CI = 1.030-1.226, P = 0.009; dominant genetic model: OR = 1.127, 95% CI = 1.037-1.224, P = 0.005). After further stratified analyses, the increased risk was observed only in the subgroups of hospital-based studies, PCR-RFLP genotyping methods, sporadic colorectal cancer, and Caucasian ethnicity.

Conclusions: The available evidence demonstrates that the CCND1 870A allele might be a low-penetrant risk factor for colorectal cancer.

Figure 1. Flow chart of study selection according to MOOSE guidelines .

Figure 2. Galbraith plot analysis of the amount of heterogeneity from all the included studies (AA vs. GG).

The y-axis shows the ratio of the log OR to its standard error (SE), and the x-axis shows the reciprocal of the SE. Each study is represented by the name of the first author. A regression line runs centrally through the name. At a 2 standard deviation distance parallel to the regression line, the 2 lines create an interval. Studies lacking in heterogeneity would lie within the 95% confidence interval (positioned 2 units above and below the central regression line).

Figure 3. The L’Abbé plot for the assessment of CRC risk in each group (G/A+A/A vs. G/G).

Each circle represents individual trial sizes, and the circles are proportional to the study weights (participant number). The diagonal dotted line indicates that the CRC risk was equal in the two arms within the trials. The solid regression line represented a summary OR of 1.127 (G/A+A/A vs. G/G), which was estimated from the pooled results of all 22 studies.

Figure 4. Begg’s funnel plot (GA vs. GG) for the identification of publication bias in all studies.