MicroRNAs are non-coding small RNAs that regulate gene expression by Watson–Crick base pairing to target messenger RNA (mRNA). They are involved in most biological and pathological processes, ...including tumorigenesis. The binding of microRNA to mRNA is critical for regulating the mRNA level and protein expression. However, this binding can be affected by single-nucleotide polymorphisms that can reside in the microRNA target site, which can either abolish existing binding sites or create illegitimate binding sites. Therefore, polymorphisms in microRNA can have a differing effect on gene and protein expression and represent another type of genetic variability that can influence the risk of certain human diseases. Different approaches have been used to predict and identify functional polymorphisms within microRNA-binding sites. The biological relevance of these polymorphisms in predicted microRNA-binding sites is beginning to be examined in large case–control studies.
To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between ...functional SNPs of ADPRT, APEX1, and XRCC1 and RP development.
We genotyped SNPs of ADPRT (rs1136410 V762A), XRCC1 (rs1799782 R194W, rs25489 R280H, and rs25487 Q399R), and APEX1 (rs1130409 D148E) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes.
We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade ≥2 RP (XRCC1: AA vs. GG, adjusted hazard ratio HR = 0.48, 95% confidence interval CI, 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001).
SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.
Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER ...genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.
In 17 previously published studies, 1,787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR; i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated OR or HR with 95% CIs to estimate the risk or hazard.
We found consistent and clinically substantial risk or hazard for TR, PFS, and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response and poor PFS and OS in Asians (TR: OR = 0.53 and 95% CI = 0.35-0.81; PFS: HR = 1.69 and 95% CI = 1.05-2.70; and OS: HR = 2.03 and 95% CI = 1.60-2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response and poor PFS and OS in Caucasians (TR: OR = 0.56 and 95% CI = 0.35-0.88; PFS: HR = 1.41 and 95% CI = 1.02-1.95; and OS: HR = 1.42 and 95% CI = 1.11-1.81).
NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin-based treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings.
Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide ...gene-environment interactions. To determine gene-asbestos interactions in lung cancer risk, we conducted genome-wide gene-environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10(-6), which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10(-5)). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene-asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk.
Efficient detection and degradation of fungicides are greatly concerned with aquatic food safety. Herein, a multifunction CoFe2O4/MoS2@Au (ACMS) composite was synthesized for crystal violet (CV) and ...malachite green (MG) photocatalytic degradation and SERS determination. As the construction of the Z-scheme heterostructure of ACMS, which enhanced the light absorption capability and the separation efficiency of photoexcited carrier significantly, ACMS possessed an excellent photocatalytic performance with a degradation rate of 94.76% for CV under simulated solar light irradiation. Furthermore, the multifunction ACMS exhibited superior SERS capability with a detection limit (LOD) of 4.309 × 10−2 μg L−1 for MG residues in water. And the ACMS substrates could be utilized to determine the MG residues in crucian carp extract, resulting in a recovery rate of 96.00~116.00%. In addition, such multifunction heterojunctions were performed for in situ monitoring of the photodegradation process. This research opened up a novel perspective on the applications of heterojunction-based multifunction materials for food safety control.
Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 ...US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in ...vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci.
Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging.
Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups.
Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression.
This study aimed to propose a novel surface-enhanced Raman spectroscopy (SERS)-based aptasensor by using 4-mercaptobenzoic acid (4-MBA) modified gold@silver core-shell nanoparticles (Au@Ag NPs) for ...detecting kanamycin for the first time with outstanding sensitivity and selectivity in the real milk samples. To achieve a high SERS activity substrate, the Au@Ag NPs with uniform shapes in a diameter of 32.2 ± 3.4 nm were synthesized successfully by seed-mediated growth and then modified with the Raman reporter 4-MBA. Under the optimal conditions, this aptamer sensing system exhibited a linear range between 6.67 × 10
− 10
g/mL and 2 × 10
− 7
g/mL with the limit of detection (142 pg/mL) of kanamycin. Moreover, the KANA-specific aptamer endowed a good specificity to this biosensor for the negative interference from other analogues (streptomycin sulfate, gentamicin sulfate, and penicillin). Finally, the aptasensor was applied in the artificially contaminated milk (1–100 ng/mL) samples and compared with the HPLC-MS technique, with the result indicating great practicality of the aptasensor. This paper has provided a potential aptasensor for simple and rapid trace-sensing of the harmful antibiotic residue in milk.
Background
Cellular immunity against tumor cells is highly dependent on antigen presentation by major histocompatibility complex class I (MHC-I) molecules. However, few published studies have ...investigated associations between functional variants of MHC-I-related genes and clinical outcomes of lung cancer patients.
Methods
We performed a two-phase Cox proportional hazards regression analysis by using two previously published genome-wide association studies to evaluate associations between genetic variants in the MHC-I-related gene set and the survival of non-small cell lung cancer (NSCLC) patients, followed by expression quantitative trait loci analysis.
Results
Of the 7811 single-nucleotide polymorphisms (SNPs) in 89 genes of 1185 NSCLC patients in the discovery dataset of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 24 SNPs remained statistically significant after validation in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. In a multivariate stepwise Cox model, three independent functional SNPs (
ERAP1
rs469783 T > C,
PSMF1
rs13040574 C > A and
NCF2
rs36071574 G > A) remained significant with an adjusted hazards ratio (HR) of 0.83 95% confidence interval (CI) = 0.77–0.89,
P
= 8.0 × 10
–7
, 0.86 (0.80–0.93,
P
= 9.4 × 10
–5
) and 1.31 (1.11–1.54,
P
= 0.001) for overall survival (OS), respectively. Further combined genotypes revealed a poor survival in a dose–response manner in association with the number of unfavorable genotypes (
P
trend
< 0.0001 and 0.0002 for OS and disease-specific survival, respectively). Also,
ERAP1
rs469783C and
PSMF1
rs13040574A alleles were associated with higher mRNA expression levels of their genes.
Conclusion
These potentially functional SNPs of the MHC-I-related genes may be biomarkers for NSCLC survival, possibly through modulating the expression of corresponding genes.
Interaction of flavonoids and enzyme may affect characteristics and physiological activities of both components. In this study, the effects of the interaction between four flavonoids (quercetin, ...luteolin, kaempferol and apigenin) and trypsin were examined. At the concentration of 2.7 mm, inhibition of trypsin (1.6 U mL⁻¹) by quercetin, luteolin, kaempferol and apigenin was 46.4%, 32.6%, 26.8% and 17.7%, respectively. In the presence of trypsin, DPPH, ABTS and hydroxyl radical scavenging activities of flavonoids were obviously inhibited. Addition of flavonoids led to fluorescence quenching of trypsin. The decreasing order of binding force between flavonoids and trypsin was quercetin, luteolin, kaempferol and apigenin. It is concluded that the interaction between flavonoids and trypsin depends on the number and position of hydroxyl group of flavonoids.
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