CAV1 polymorphisms rs1049334, rs1049337, rs7804372 might be the potential risk in tumorigenicity of urinary cancer: A systematic review and meta-analysis

Abstract

Background As an integral membrane, Caveolin-1 (CAV1), is a pivotal component to make up the caveolae protein. It has been demonstrated to influence tumorigenicity, including bladder, colon, liver, stomach, breast and lung cancer. Several publications had illustrated the relationship of between CAV1 polymorphism and urinary cancer, but the results were not consistent. We performed a comprehensive meta-analysis to explore the associations and remove the fog. Material and methods Extensive retrieve was performed in PubMed, Embase, Medline, Web of Science, CNKI, and Wanfang database up to September, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger's test and Begg's funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was managed to demonstrate the relationship of polymorphism and CAV1 mRNA expression level. Results 34 case-control studies with a total of 13,778 cancer cases and 20,581 healthy controls were enrolled into the meta-analysis. The polled result shown that an increased risk of rs1049334 polymorphism on urinary cancer were reveled in homozygote comparison model (MM vs. WW: OR = 1.240, 95% CI = 1.052-1.462, P = 0.011) and recessive comparison model (MM vs. MW + WW: OR = 1.198, 95% CI = 1.018-1.410, P = 0.030). What's more, rs17878467 polymorphism may play a protect role in the tumorigenesis of urinary cancer, shown in heterozygote comparison model (MW vs. WW: OR = 0.882, 95% CI = 0.78-0.999, P = 0.048). For rs7804372, the overall pooled results revealed a reducing risk in allelic contrast model (M vs. W: OR = 0.734, 95%CI = 0.544-0.99, P = 0.043), homozygote comparison model (MM vs. WW: OR = 0.532, 95% CI = 0.313-0.905, P = 0.020) and recessive comparison model (MM vs. MW + WW: OR = 0.580, 95% CI = 0.437-0.77, P < 0.001). In the stratified analyses by cancer types, the risk of PCa is downgrade by rs7804372 in all five genetic models. The GTEx in-silico analysis index that the polymorphism of CAV1 influence its mRNA expression by a dose-dependent effective of its mutant allele. Conclusion rs1049334 polymorphismof CAV1 upgrade the risk of urinary cancer, while rs1049337 and rs7804372 polymorphisms may act as a protector of urinary cancer. Further large and well-designed studies in various populations are needed to confirm the results.

Keywords: CAV1; Caveolin-1; Meta-analysis; Polymorphism; Urinary cancer.