Abstract
Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (−842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (−842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62–0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64–0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (−842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity.
Highlights
Cancer is a multifactorial disease that results from complex interactions between numerous genetic and environmental factors [1]
A total of seven articles in English regarding the PIN1 promoter polymorphism (‐842 G>C) and cancer risk were available for the present meta‐analysis
It was found that individuals exhibiting the variant GC and GC/CC genotypes were significantly associated with a decreased risk of cancer, breast and lung cancer, which was revealed by the subgroup analysis
Summary
Cancer is a multifactorial disease that results from complex interactions between numerous genetic and environmental factors [1]. PIN1 substrates, which contain phospho‐Ser/Thr‐Pro motifs, include a number of important cell cycle regulators, as well as oncogenic and tumor suppressor proteins These include cyclin D1 [7], p53 [8], Cdc25 [9], c‐Myc [10], c‐Jun [8], β‐catenin [11], glycogen synthase kinase‐3β [10] and Bcl‐2 [12]. By targeting these significant substrates, which contain phospho‐Ser/Thr‐Pro motifs, PIN1‐induced conformational changes may function as a critical catalyst for the potentiation of multiple oncogenic signaling pathways during cancer development [13].
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