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

Abstract

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.

Association of CCND1 rs603965 Polymorphism with Breast Cancer Risk in North Indian Population

“…In the present study on the association between CCND1 G870A and risk of breast cancer, A/A genotype in CCND1 found associated significantly with the breast cancer risk in total and premenopausal women with ORs 2.66 and 3.35, respectively, which is in corroboration with several studies showing that CCND1 870A was associated with increased risk of many other types of cancers, such as urinary bladder cancer (Wang et al, 2002), esophagus and gastric cancer (Zhang et al, 2003), prostate cancer (Wang et al, 2003), squamous cell carcinoma of the head and neck (Zheng et al, 2001), colorectal cancer (Xie et al, 2017) and cervical cancer (Ni et al, 2011). We also found many recent corroborating reports from India suggesting an association between 870AA genotype and an increased risk for the development of cervical (Thakur et al, 2018), prostate (Mandal and Mittal 2012), urinary bladder (Gangwar and Mittal 2010) and esophageal (Hussain et al, 2011) cancer.…”

“…Several molecular epidemiological studies have been conducted to examine the association between CCND1 G870A polymorphism and breast cancer risk (Akhter et al, 2019;Ceschi et al, 2005;Lu et al, 2009;Thakur et al, 2018;Yu et al, 2008;Zhang et al, 2016), but the results remain inconsistent. In the present study on the association between CCND1 G870A and risk of breast cancer, A/A genotype in CCND1 found associated significantly with the breast cancer risk in total and premenopausal women with ORs 2.66 and 3.35, respectively, which is in corroboration with several studies showing that CCND1 870A was associated with increased risk of many other types of cancers, such as urinary bladder cancer (Wang et al, 2002), esophagus and gastric cancer (Zhang et al, 2003), prostate cancer (Wang et al, 2003), squamous cell carcinoma of the head and neck (Zheng et al, 2001), colorectal cancer (Xie et al, 2017) and cervical cancer (Ni et al, 2011).…”

Pancreatic stellate cells exhibit adaptation to oxidative stress evoked by hypoxia

“…Additional evidence for an increase of PSC proliferation under hypoxia are shown by the increase in the expression of cyclin D that we observed. This protein is a key regulator of the cell cycle and division (Roskoski, 2016; Thakur et al., 2018). Another major regulator of progression through the cell cycle is cyclin A (Wang et al., 2018).…”

Genetic Variants Related to Cell Cycle and Stability of Telomere in Patients with Glioma

“…A casuistic study can also not be done in association of cyclin D1 with gliomas (Aytekin et al, 2014). On the other hand, there are references of the association between polymorphism and thyroid and breast cancer ((Jeon et al, 2018;Thakur et al, 2018), however the scarce ones are studies in Brazilian population. Cyclin D1, encoded by the CCND1 gene, is an important regulatory protein of the G1 phase transition to a phase of the cell cycle and has a great impact on the control of cell proliferation and differentiation (Zhang et al, 2011).…”