Association of genetic polymorphisms in PTEN and additional gene-gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population

Abstract

This study aims to investigate the association of five single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homologue (PTEN) gene and additional role of gene-gene interaction with esophageal squamous cell carcinoma (ESCC), based on a Chinese case-control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case-control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio (OR) and 95% confident interval (95%CI) were calculated. All genotypes were distributed according to Hardy-Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild-type homozygotes, and OR (95%CI) were 1.27 (1.09-2.08) and 1.45 (1.17-1.98), respectively. We also found a potential gene-gene interaction between rs2735343 and rs701848 (P = 0.0010), and a potential gene-gene interaction among all five SNP (P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37-3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene-gene interaction between rs2735343 and rs701848 and a potential gene-gene interaction among all five SNPs.

The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes

“…The major finding was a significant association of PTEN rs701848 TC/CC genotypes and C allele and AKT rs2494752 AG/AA genotype with an increased BC risk under a dominant model in a relatively large cohort (n=920). Our finding that PTEN rs701848 polymorphism predicted the individual susceptibility to the development of BC is similar to the results from the studies reported in other tumors such as colorectal cancer, esophageal squamous cell carcinoma (ESCC)[8, 12, 22]. PTEN rs701848 SNP is located at 3′-UTR region, which can be targeted by microRNAs, and might alter the strength of microRNAs binding site near the SNP rs701848, thus influencing gene regulation and protein expression.…”

“…Lin’ study on colorectal cancer (CRC) [12] reported that patients with rs701848 TC/CC genotype in the dominant model and C allele were more likely to be increased CRC risk than carrying CC genotype patients. Xu et al [8] revealed that the carriers of homozygous mutant of rs701848 polymorphism increased ESCC risk than those with wild-type homozygotes. It is worthy to note that in another 2 case-control studies, one observed that the distribution of genotypes or alleles at PTEN rs701848 T/C possessing notably higher proportion in ESCC cases (n=304) than in the controls (n=413) [6], however, the other study did not found any significant differences of the genotype in PTEN rs701848 in ESCC patients (n=226) [18].…”

“…Recent numerous genomic studies reported that breast cancer consists of a complex biological process with patient-specific genetic variations [4]. The single nucleotide polymorphisms (SNPs) in many candidate genes, especially in signal transduction pathways including the phosphatase and tensin homolog deleted on chromosome10 (pTEN)/phosphatidylinositol-4,5- bisphosphate 3-kinase catalytic subunit alpha (PI3K)/AKT serine/threonine kinase 1(AKT) signaling pathway, often contribute to the origin, propagation, and treatment responses of a cancer and prognosis [5–8]. Therefore, improving the treatment efficacy and prognosis prediction requires a better understanding of the genetic risk factors that involve in the breast cancer carcinogenesis.…”

PIM1 polymorphism and PIM1 expression as predisposing factors of esophageal squamous cell carcinoma in the Asian population

“… 16 Recently, progress has been made in diagnosis and therapeutic options for ESCC, particularly in exploring its relationship with gene polymorphisms. 17 , 18 PIM1 is a proto-oncogene that encodes a serine/threonine kinase with multiple cellular functions involving the regulation of cell apoptosis and progression, as well as transcription through various signaling pathways, including the STAT3 → PIM1 → NFkappaB stress response pathway and signaling pathways downstream of Akt. 19 – 21 Accumulating evidence has demonstrated that PIM1 plays an important role in tumor progression, including colon cancer, laryngeal cancer, lymphocytic leukemia, and head and neck squamous cell carcinomas.…”

Chromosomal and Genomic Variations in Esophageal Squamous Cell Carcinoma: A Review of Technologies, Applications, and Prospections

“…Two common methods for the detection of real-time qPCR products are: (1) non-specific fluorescent dyes that intercalate with any double-stranded DNA, such as SYBR Green method, This method is a low cost and accurate way for detection of gene copy number alteration (CNA), including copy number amplification 31 and deletion 32 ; (2) sequence-specific DNA probes consisting of oligonucleotides that are labelled with a fluorescent reporter which permits detection only after hybridization of the probe with its complementary sequence, such as TaqMan probe method. A series of TaqMan Assays were designed to detect SNP 33 , CNA 34 and gene mutation. This method contains a specific DNA probe, which improves the specificity and sensitivity for detection, with a wider application, a higher accuracy than SYBR Green method, however, a higher cost.…”