Association between Cyclin D1 G870A (rs9344) polymorphism and cancer risk in Indian population: Meta-analysis and Trial Sequential Analysis

Introduction: Association between Cyclin D1 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 twelve studies including 3739 subjects was collected using Pubmed and Embase . RevMan 5.3 was used to perform the meta-analysis. OR with 95% CI were calculated to establish the association. Results: CCND1 polymorphism was not significantly associated with overall cancer risk in all the genetic models [dominant: GG vs GA+AA: OR(95%CI)=0.81(0.60-1.09) p=0.17; recessive: GG+GA vs AA: OR(95%CI)=1.23(0.96-1.59) p=0.11;co-dominant: GG vs AA: OR(95% CI)=1.35(0.93-1.97) P=0.12; co-dominant: (GG vs GA: OR(95% CI)=1.16(0.85-1.59) P=0.34; allelic: A vs G: OR(95%CI)=1.20(1.14-2.85) p=0.23; allelic: G vs A: OR(95%CI)=0.83(0.62-1.12) p=0.23]. Subgroup analysis presented significant association between  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 (G vs A: OR=1.63, 95%CI=1.22-2.19, p=0.001). An increased esophageal cancer risk in recessive (GG+GA vs AA: OR=1.51, 95%CI=1.05-2.16, p=0.03) and co-dominant (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). The trial sequential analysis showed that the present meta-analysis is inconclusive.  Conclusion: CCND1 polymorphism 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. Future studies with larger sample size are required to draw a reliable conclusion.