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

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.