Abstract
PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.
Highlights
Cancer is a multi-step process resulting from complex interactions between genetic and environmental factors
Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: Odds ratios (ORs)= 0.697, 95%confidence intervals (CIs): 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians
For -667C>T polymorphism, some studies found that -667T allele was associated with increased risk of nasopharyngeal carcinoma (Lu et al, 2013) and hepatocellular carcinoma (Segat et al, 2007), but others found that this polymorphism had no association with esophageal carcinoma (You et al, 2013), lung cancer (Lu et al, 2011), breast cancer (Han et al, 2010; Naidu et al, 2011) and squamous cell carcinoma of the head and neck (Lu et al, 2009)
Summary
Cancer is a multi-step process resulting from complex interactions between genetic and environmental factors. Host genetic susceptibility plays an important role in developing cancer Such various susceptibilities could be explained, in part, by single nucleotide polymorphisms (SNPs) of susceptible genes (Xue et al, 2010; Chung et al, 2011; Perez-Losada et al, 2011). For -667C>T polymorphism, some studies found that -667T allele was associated with increased risk of nasopharyngeal carcinoma (Lu et al, 2013) and hepatocellular carcinoma (Segat et al, 2007), but others found that this polymorphism had no association with esophageal carcinoma (You et al, 2013), lung cancer (Lu et al, 2011), breast cancer (Han et al, 2010; Naidu et al, 2011) and squamous cell carcinoma of the head and neck (Lu et al, 2009). To further evaluate the association between Pin polymorphisms (-842G>C, rs2233678 and -667C>T, rs2233679) and the risk of cancer, a metaanalysis was conducted on all eligible published studies in current study
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