Downregulated expression of hsa_circ_0037515 and hsa_circ_0037516 as novel biomarkers for non-small cell lung cancer.

Circular RNAs (circRNAs) represent a class of endogenous non-coding RNAs. Recently, it has been reported that circRNAs might serve as novel potential biomarkers for the diagnosis of cancer, including non-small cell lung cancer (NSCLC). Mutations in the ATP binding cassette subfamily A member 3 (ABCA3) have been increasingly associated with lung disease; however, roles for circRNAs at the ABCA3 locus have not been identified. To characterize novel biomarkers in NSCLC, a bioinformatics platform was used to select circRNAs within the ABCA3 gene. Divergent primers were designed for hsa_circ_0037515 and hsa_circ_0037516, and the PCR products were sequenced to verify their existence in lung tissue. To evaluate diagnostic potential, expression levels of hsa_circ_0037515, hsa_circ_0037516, and ABCA3 were measured by quantitative reverse transcription-polymerase chain reaction; differences in expression levels were analyzed using the paired t-test, and receiver operating characteristic (ROC) curves were established. Our results demonstrate that ABCA3 mRNA, hsa_circ_0037515, and hsa_circ_0037516 are significantly downregulated in 61 paired samples of NSCLC compared to adjacent lung tissues (P < 0.01), and that the areas under the ROC curves for the two circRNAs (0.81 and 0.82, respectively) are indicative of diagnostic value. Furthermore, the significance was improved by considering the two circRNAs in combination (area under the ROC curve, 0.90). Our results suggest that hsa_circ_0037515 and hsa_circ_0037516 serve as novel potential biomarkers for the diagnosis of NSCLC.

Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population.

Non-small cell lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Genetic variants in regulatory regions of some miRNAs might be involved in non-small cell lung cancer susceptibility and survival. rs12220909 (G/C) genetic polymorphism in miR-4293 has been shown to be associated with decreased risk of esophageal squamous cell carcinoma. However, the influence of rs12220909 genetic variation on non-small cell lung cancer susceptibility has not been reported. In order to evaluate the potential association between miR-4293 rs12220909 and non-small cell lung cancer risk in a Chinese population, we performed a case-control study among 998 non-small cell lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was significantly associated with decreased susceptibility to non-small cell lung cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR = 0.687, 95%CI = 0.564-0.837, P = 1.95E-4), which indicates that rs12220909 in miR-4293 may play a significant role in the development of non-small cell lung cancer.

miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population.

Esophageal cancer is one of the most aggressive cancers in the world, 70% of which are from China and esophageal squamous cell carcinoma (ESCC) is the major histopathological form (>90%). The single nucleotide polymorphisms (SNPs) in mature sequence of microRNA (miRNA) (mmSNPs) could cause the alteration of microRNA expression and contribute to the susceptibility of cancers. To evaluate the association between mmSNPs and ESCC, a case-control study including 773 patients with ESCC and 882 gender- and age-matched controls was carried out to investigate the association of five mmSNPs (miR-449b rs10061133, miR-4293 rs12220909, miR-608 rs4919510, miR-627 rs2620381, and miR-646 rs6513497) with ESCC susceptibility. As a result, two SNPs, miR-449b rs10061133 and miR-4293 rs12220909, were associated with decreased ESCC risk. For miR-449b rs10061133 A>G, individuals carrying GG genotype had an odds ratio (OR) of 0.77 (95% confidence interval (95% CI) 0.62-0.97) compared with individuals with AA genotype. In the recessive model, the GG genotype also showed a protective effect on ESCC (OR = 0.78, 95% CI 0.63-0.97). For miR-4293 rs12220909 G>C, the heterozygous genotype GC was associated with a decreased ESCC risk (OR = 0.77, 95% CI 0.61-0.97) compared with GG genotype. The C allele conferred 23% decrease in ESCC risk compared with the G allele in the allelic model (95% CI 0.63-0.93). In the dominant model, the GC/CC genotypes decreased the risk of ESCC (adjusted OR = 0.77, 95% CI 0.61-0.96). This study provides the first evidence that miR-449b rs10061133 and miR-4293 rs12220909 are associated with ESCC risk in Chinese population.

Sulfotransferase SULT1A1 Arg213His polymorphism with cancer risk: a meta-analysis of 53 case-control studies.

BACKGROUND: The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis. METHODS: Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI). RESULTS: A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR  1.09, 95% CI = 1.01-1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01-1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02-1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11-2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13-2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10-2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22-3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected. CONCLUSIONS: The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn't show any association with breast cancer, but the possible risk in Asian population needs further investigation.