Association Between G870A (rs9344) Polymorphism and Cancer Risk in Indian Population: Meta-analysis and Trial Sequential Analysis

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 variant and overall cancer risk in Indian population. Data from 12 published studies including 3739 subjects were collected using and was used to perform the meta-analysis. OR with 95%CI were calculated to establish the association. Overall, the cumulative findings demonstrated that 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), =0.17; recessive model: GG+GA vs AA: OR (95%CI) = 1.23 (0.96-1.59), =0.11; co-dominant model: co-dominant model: ; allelic model: A vs G: OR (95%CI) = 1.20 (1.14-2.85), =0.23; allelic model: G vs A: OR (95%CI) = 0.83 (0.62-1.12), =0.23). Subgroup analysis according to cancer types presented significant association of polymorphism and increased breast cancer risk in dominant model (GG vs GA+AA: OR = 2.75, 95%CI = 1.54-4.90, =0.0006) and allelic model (G vs A: OR = 1.63, 95%CI = 1.22-2.19, =0.001). An increased esophageal cancer risk in recessive model (GG+GA vs AA: OR = 1.51, 95%CI = 1.05-2.16, =0.03) and co-dominant model (GG vs AA: OR = 2.51, 95%CI = 1.10-5.71, =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, =0.004 and GG vs GA: OR = 1.74, 95%CI = 1.14-2.67, =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, =0.38) with reference to 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. 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.