Functional polymorphisms in PIN1 promoter and esophageal carcinoma susceptibility in Chinese population

Abstract

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), which regulates the conformation of Pro-directed phosphorylation sites, has been identified as a critical catalyst involved in multiple oncogenic signaling pathways. Recently, it has been demonstrated that several putative functional polymorphisms of PIN1 gene were associated with cancer risk. This study examined whether genetic polymorphisms in promoter of PIN1 are associated with esophageal carcinoma susceptibility. Two common polymorphisms in PIN1, rs2233678 (-842G>C) and rs2233679 (-667C>T) were genotyped in this hospital-based case-control study of 699 esophageal carcinoma patients and 729 healthy controls. The results revealed that compared with the most common -842GG genotype carriers, the carriers of -842C variant genotypes (GC+CC) had significantly decreased risk of esophageal carcinoma [odds ratio (OR) = 0.55, 95 % CI = (0.40-0.75), P = 0.001]. No association was observed between the -667C>T polymorphism and the risk of esophageal carcinoma. Furthermore, we found that the haplotype of 'C(-842)-C(-667)' had a greater protected effect [OR = 0.67, 95 % CI = (0.47-0.96), P = 0.021]. Functional assay revealed that -842C variant genotypes (GC+CC) carriers had a lower transcription activity and mRNA expression level than the -842GG carriers. These results indicated that -842G>C genetic variant in PIN1 promoter may decrease the promoter activity, resulting in changes in the levels of PIN1 and modifying cancer susceptibility.

Lack of association between the PIN1 promoter −667T>C (rs2233679) polymorphism and cancer risk: Evidence from meta-analysis

“…Recently, Lu et al (21) showed that the PIN1 promoter (-667T>C) polymorphism was associated with a decreased risk of nasopharyngeal carcinoma (NPC) in Chinese populations. However, it has been indicated that the variant -667C allele was not associated with risk of cancer (16,(18)(19)(20)22). To resolve this conflict, we performed a meta-analysis of seven published case-control studies including 4,524 cases with different tumor types and 4,561 controls to derive a more precise estimation of the association.…”

“…Several putative functional single-nucleotide polymorphisms (SNPs) have been identified in the coding and promoter regions of PIN1, the most common one being rs2233679T>C: c.-667T>C in the promoter. The association between PIN1 promoter (-667T>C) polymorphism and risk of cancer of various organs, including (18,19), squamous cell carcinoma of the head and neck (20), nasopharyngeal cancer (21) and esophageal cancer (22) has been recently investigated. However, the results of those studies remain controversial.…”

Pin1 Promoter rs2233678 and rs2233679 Polymorphisms in Cancer: A Meta-analysis

“…We reviewed the titles, abstracts and the full texts of all retrieved articles through defined criteria. Finally, 9 studies including a total of 5427 cancer cases and 5469 controls were selected in our meta-analysis (Segat et al, 2007;Lu et al, 2009;Zhao, 2009;Han et al, 2010;Lu et al, 2011;Naidu et al, 2011;Cao, 2012;Lu et al, 2013;You et al, 2013) (Figure 1). The characteristics of the selected studies are listed in Table 1.…”

“…For the -842G>C polymorphism, Han et al (2010) found that -842C variant alleles (GC+CC) were associated with decreased risk in breast cancer; Lu at al (Lu et al, 2013) found that -842CG heterozygote but not -842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma; In another two studies, -842G>C polymorphism had no influence on breast cancer (Naidu et al, 2011) and hepatocellular carcinoma risk (Segat et al, 2007). 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 , breast cancer (Han et al, 2010;Naidu et al, 2011) and squamous cell carcinoma of the head and neck (Lu et al, 2009). Therefore, it is highly necessary to perform a quantitative and systematic investigation with rigorous methods.…”

PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population

“…Several studies have revealed the relationship between the PIN1 gene polymorphisms, rs2233678, rs2233679, and rs2233682, and the susceptibility of cancers, such as esophageal carcinoma, nasopharyngeal carcinoma, lung cancer, breast cancer, and squamous cell carcinoma of the head and neck (SCCHN), in various races [22][23][24][25][26]. However, to date, only one study has investigated the influence that PIN1 gene polymorphisms have on the risk of HCC [27].…”