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To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer (GC), we performed two genome-wide association studies (GWASs) of GC survival in the Jiangsu (N= 1049) and Shanghai (N= 1405) cohorts. By using a TCGA dataset, we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci. Then, we constructed a weighted polygenic hazard score (PHS) and developed a nomogram in combination with clinical variables. We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic (ROC) curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We identified a single nucleotide polymorphism (SNP) of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a Pvalue of 4.12 × 10−8, and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort. The PHS derived from these 26 SNPs (PHS-26) was an independent prognostic factor for GC survival (all P< 0.001). The 5-year AUC of PHS-26 was 0.68, 0.66 and 0.67 for Jiangsu, Shanghai and their pooled cohorts, respectively, which increased to 0.80, 0.82 and 0.81, correspondingly, after being integrated into a nomogram together with variables of the clinical model. The PHS-26 could improve the NRIs by 16.20%, 4.90% and 8.70%, respectively, and the IDIs by 11.90%, 8.00% and 9.70%, respectively. The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.

The pressure for agriculture security is a problem that affects human community at multiple levels, involving the production of agricultural commodities, the management of agricultural water and soil, and postharvest transport and storage. To date, agriculture security is increasingly becoming a challenge due to the abuse of chemicals, the indiscriminate discharge of wastewater, and the improper storage of agricultural products. As such, the determination and removal of hazardous contaminants in agricultural production chains are indispensable. As a fascinating semiconductor, molybdenum disulfide (MoS2), with controllable structure, appealing photoelectric properties, and superior physicochemical stability, is regarded as a promising material for the control of agricultural contaminants. This critical review summarizes the synthetic strategies for MoS2and related efforts for agricultural contaminant control. It begins with the synthetic methods of the materials based on different principles. Subsequently, the determination and removal strategies based on MoS2and its composites are discussed. The third part focuses on the description of MoS2-based platforms for control of different agricultural contaminants (heavy metals, pesticides, mycotoxins, antibiotics, and organic dyes). Finally, the challenges and potential opportunities for MoS2application in modern agriculture are discussed.

Aquaculture fungicide causes threats to the human community and their sensitive detection are thus essential for food safety. Herein, MoS2/g-C3N4@Au heterojunction-based recyclable SERS substrate was developed for fungicide detection. The optimal substrate exhibited good SERS performance with a detection limit as low as 9.908 × 10−5mg L−1for malachite green (MG). Furthermore, an MCN@Au-based photodegradation of crystal violet (CV) under simulated light irradiation was realized, resulting in a degradation rate of 95.6%. With the dual function of the as-synthesized materials, good reusability of the substrates for at least six “detection-degradation” cycles was achieved. In addition, the MG in prawn extract could be sensitively determined with a satisfactory recovery from 91.60 to 124.00%. This work paves an avenue for the fabrication of heterojunction-based recyclable SERS substrates and provides a novel weapon for food safety protection.

Despite prohibition in many countries, malachite green (MG) and crystal violet (CV) are illegally used in aquaculture, endangering both human health and the environment. Therefore, it is crucial to develop a method to accurately detect MG and CV. Surface-enhanced Raman spectroscopy (SERS) technology based on noble metal materials has attracted considerable attention for detecting food contaminations. However, noble metal materials are of poor stability and have a very low affinity for organic molecules. Herein, in this study, covalent organic frameworks (COFs) modified with silver nanoparticles (Ag NPs) were used as SERS substrates for the adsorption and detection of fungicides. COFs prepared by the Schiff base reaction of 1,3,5-tris (4-aminophenyl) benzene (TAPB) and 2,5-dimethoxybenzene-1,4-dicarboxaldehyde (DMTA) had a huge specific surface area and could provide sufficient adsorption sites and Ag NPs grown on the surface of COFs not only generated dense SERS “hot spots” but also improved their stability. The results showed that COF@Ag NPs exhibited a high enhancement factor (1.4 × 106), high reproducibility (RSD = 6.18%), and good stability within 50 days (RSD = 8.88%). Regression analyses in the ranges of 0.0001–10.0 mg/L and 0.0002–10.0 mg/L showed that the limits of detection (LOD) for the standard solutions of MG and CV were 3.8 × 10−5mg/L and 1.8 × 10−5mg/L, respectively. Furthermore, for MG and CV in fish samples, significant recoveries of 90.83–107.91% and 98.60–116.69% were achieved. Hence, it is hoped that this work could expand the application of COF materials for trace detection in SERS analyses.

Background The incidence of nonmelanoma skin cancer (NMSC) is equivalent to that of all other cancers combined. Previously, we mapped the 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion susceptibility locus, Psl1, to distal chromosome 9 in crosses of sensitive DBA/2 mice with relatively resistant C57BL/6 mice. Here, we used the mouse two-stage skin carcinogenesis model to identify the gene(s) responsible for the effects of Psl1. Methods Interval-specific congenic mouse strains (n [greater than or equal to] 59 mice per strain) were used to more precisely map the Psl1 locus. Having identified glutathione S-transferase [alpha]4 (Gsta4) as a candidate tumor promotion susceptibility gene that mapped within the delimited region, we analyzed Gsta4-deficient mice (n = 62) for susceptibility to skin tumor promotion by TPA. We used quantitative polymerase chain reaction, western blotting, and immunohistochemistry to verify induction of Gsta4 in mouse epidermis following TPA treatment and biochemical assays to associate Gsta4 activity with tumor promotion susceptibility. In addition, single-nucleotide polymorphisms (SNPs) in GSTA4 were analyzed in a case-control study of 414 NMSC patients and 450 control subjects to examine their association with human NMSC. Statistical analyses of tumor studies in mice were one-sided, whereas all other statistical analyses were two-sided. Results Analyses of congenic mice indicated that at least two loci, Psl1.1 and Psl1.2, map to distal chromosome 9 and confer susceptibility to skin tumor promotion by TPA. Gsta4 maps to Psl1.2 and was highly induced (mRNA and protein) in the epidermis of resistant C57BL/6 mice compared with that of sensitive DBA/2 mice following treatment with TPA. Gsta4 activity levels were also higher in the epidermis of C57BL/6 mice following treatment with TPA. Gsta4-deficient mice (C57BL/6.[Gsta4.sup.-/-] mice) were more sensitive to TPA skin tumor promotion (0.8 tumors per mouse vs 0.4 tumors per mouse in wild-type controls; difference = 0.4 tumors per mouse; 95% confidence interval = 0.1 to 0.7, P = .007). Furthermore, inheritance of polymorphisms in GSTA4 was associated with risk of human NMSC. Three SNPs were found to be independent predictors of NMSC risk. Two of these were associated with increased risk of NMSC (odds ratios [ORs] = 1.60 to 3.42), while the third was associated with decreased risk of NMSC (OR = 0.63). In addition, a fourth SNP was associated with decreased risk of basal cell carcinoma only (OR = 0.44). Conclusions Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans. DOI: 10.1093/jnci/djq392

Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10244 head and neck cancer case subjects and 15227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology. DOI: 10.1093/jnci/djk179

Background: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. Methods: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P

Background: The mechanism underlying the role of UV light exposure from sunlight in the etiology of cutaneous malignant melanoma (CMM) is unclear. Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of CMM, which suggests that DNA repair capacity (DRC) plays a role in sunlight-induced CMM in the general population as well. Methods: We conducted a hospital-based case--control study of DRC and CMM among 312 non-Hispanic white CMM patients who had no prior chemotherapy or radiation therapy, and 324 cancer-free control subjects who were frequency-matched to case patients on age, sex, and ethnicity. Information on demographic variables, risk factors, and tumor characteristics was obtained from questionnaires and medical records. We used the host-cell reactivation assay to measure the DRC in study subjects' lymphocytes. All statistical tests were two sided. Results: Case patients had a 19% lower mean ([+ or -] standard deviation [SD]) DRC (8.5 [+ or -] 3.4%) than control subjects (10.5 [+ or -] 5.1%), a statistically significant difference (P

Background: Non-small-cell lung cancer (NSCLC) is frequently resistant to chemotherapy, and this resistance has been associated with elevated nucleotide excision repair (NER) in tumor tissue. We hypothesized that patients with NSCLC who had effective systemic (host) NER would have poorer survival than patients with suboptimal NER and that the association between NER effectiveness and survival would be most marked in patients receiving chemotherapy. Methods: 375 patients with newly diagnosed NSCLC were accrued for a case-control study between July 1995 and December 1999. NER activity was estimated as the DNA repair capacity (DRC) measured in the patient's peripheral lymphocytes by the host cell reactivation assay. Cox proportional hazards models were used to assess the association between DRC and survival. All statistical tests were two-sided. Results: For every unit (percentage) increase in DRC, the relative risk (RR) of death was 1.05 (95% confidence interval [CI] = 1.00 to 1.10; P = .05) for the 345 patients for whom weight loss information was available and 1.06 (95% CI = 1.00 to 1.12; P = .03) for the 275 patients with complete follow-up information. In 86 patients treated with chemotherapy only, the RR of death increased to 1.11 (95% CI = 1.02 to 1.21; P = .01) for every unit (percentage) increase in DRC. Of those 86 patients, patients in the top quartile of the DRC distribution were at twice the RR of death as those in the lowest quartile (RR = 2.72; 95% CI = 1.24 to 5.95; P = .01). Effective DRC was not a risk factor for death in patients who were not treated with chemotherapy. Conclusions: Our data suggest that effective host DRC may be associated with poorer survival in patients with NSCLC who are treated with chemotherapy.

Background: About 9% of human cancers are brain tumors, of which 90% are gliomas. [gamma]-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to [gamma]-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the [gamma]-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. Methods: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We [gamma]-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. Results: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P

Plasmonic Au–Ag core–shell nanorods (Au@Ag NRs) have drawn great attention and are widely used in surface-enhanced Raman scattering (SERS) due to their distinctive local surface plasmon resonance peculiarities. To optimize the thickness of the Ag shell, the electromagnetic field distribution of Au@Ag NRs was firstly simulated using the Radiofrequency module of COMSOL. Then, Au@Ag NRs with different shell thicknesses were prepared by coating different amounts of silver nitrate, and the Raman signal of the molecule of 4-mercaptobenzoic acid was measured to evaluate the SERS activity of the prepared Au@Ag NRs. The experimental results showed that the Au@Ag NRs with the shell thickness of 7.51 nm performed the best SERS effect. Finally, the optimized Au@Ag NRs were used to detect thiram solution and a low limit of detection of 0.003 mg/L was achieved, indicating that the optimized Au@Ag NRs might be a promising substrate for pesticide residues detection.

ObjectiveAlthough a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their mechanisms in GC development.DesignWe conducted a meta-analysis of four genome-wide association studies (GWASs) encompassing 3771 cases and 5426 controls. After targeted sequencing and functional annotation, we performed in vitro and in vivo experiments to confirm the functions of genetic variants and candidate genes. Moreover, we selected 33 promising variants for two-stage replication in 7035 cases and 8323 controls from other five studies.ResultsThe meta-analysis of GWASs identified three loci at 1q22, 5p13.1 and 10q23.33 associated with GC risk at p<5×10−8 and replicated seven known loci at p<0.05. At 5p13.1, the risk rs59133000[C] allele enhanced the binding affinity of NF-κB1 (nuclear factor kappa B subunit 1) to the promoter of PRKAA1, resulting in a reduced promoter activity and lower expression. The knockout of PRKAA1promoted both GC cell proliferation and xenograft tumour growth in nude mice. At 10q23.33, the rs3781266[C] and rs3740365[T] risk alleles in complete linkage disequilibrium disrupted and created, respectively, the binding motifs of POU2F1 and PAX3, resulting in an increased enhancer activity and expression of NOC3L, while the NOC3Lknockdown suppressed GC cell growth. Moreover, two new loci at 3q11.2 (OR=1.21, p=4.56×10−9) and 4q28.1 (OR=1.14, p=3.33×10−11) were associated with GC risk.ConclusionWe identified 12 loci to be associated with GC risk in Chinese populations and deciphered the mechanisms of PRKAA1at 5p13.1 and NOC3Lat 10q23.33 in gastric tumourigenesis.

Genetic variation has an important role in the development of non-small-cell lung cancer (NSCLC). However, genetic factors for lung cancer have not been fully identified, especially in Chinese populations, which limits the use of existing polygenic risk scores (PRS) to identify subpopulations at high risk of lung cancer for prevention. We therefore aimed to identify novel loci associated with NSCLC risk, and generate a PRS and evaluate its utility and effectiveness in the prediction of lung cancer risk in Chinese populations.

The high sensitivity and long-term storage stability of a plasmonic substrate are vital for practical applications of the surface-enhanced Raman scattering (SERS) technique in real-world analysis. In this study, a rationally designed, ternary film-packaged, silver-coated gold-nanoparticle (Au@Ag NP) plasmonic array was fabricated and applied as a stable and high-performance SERS chip for highly sensitive sensing of thiabendazole (TBZ) residues in fruit juices. The ternary films played different roles in the plasmonic chip: a newborn poly(methyl methacrylate) (PMMA) film serving as a template for fixing the self-assembled closely packed monolayer Au@Ag NP array that provided an intensive hot spot, a fluorescent quantitative polymerase chain reaction adhesive film (qPCR film) acting as a carrier to retrieve the Au@Ag/PMMA film that was used to improve the robustness of the plasmonic array, and a polyethylene terephthalate (PET) film covered over the Au@Ag/PMMA/qPCR film performing as a barrier to improve the stability of the chip. The Au@Ag/PMMA/qPCR-PET film chip showed high sensitivity with an enhancement factor of 3.14 × 106, long-term storage stability without changing SERS signals for more than 2 months at room temperatures, and a low limit of detection for sensing TBZ in pear juice (21 ppb), orange juice (43 ppb), and grape juice (69 ppb). In addition, the procedure for fabricating the Au@Ag/PMMA/qPCR-PET film SERS chip was easy to handle, offering a new strategy to develop flexible and wearable sensors for on-site monitoring of chemical contaminants with a portable Raman spectrometer in the future.

Background: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. Methods: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. Results: Overall, lower DRC was observed in case patients than in control subjects (P [is less than] .001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2.0 with 95% CI = 1.2-3.4, and OR = 4.3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; [P.sub.trend] [is less than] .001). Case patients who were younger at diagnosis ([is less than] 60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. Conclusion: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies. [J Natl Cancer Inst 2000;92:1764-72]

Rapid and accurate measurement of polyphenol oxidase (PPO) activity is important in the food industry as PPOs play a vital role in catalyzing enzymatic reactions. The aim of this study was to develop surface-enhanced Raman scattering (SERS) approach for accurate determination of PPO activity in fruit and vegetables using the reduction in SERS intensity of catechol in reaction medium. Within a certain catechol concentration, when a purified PPO solution was analyzed, the reduction in SERS intensity (ΔI) was linear to PPO activity (Ec) in a wide range of 500–50 000 U/L, and a linear regression equation of log ΔI/Δt= 0.6223 log Ec+ 0.8072, with a correlation coefficient of 0.9689 and a limit of detection of 224.65 U/L, was obtained. The method was used for detecting PPO activity in apple and potato samples, and the results were compared with those obtained from colorimetric assay, which demonstrated that the proposed method could be successfully used for detecting PPO activity in food samples.

The DNA repair capacity (DRC) of tumor cells is an important contributor to resistance to radiation and platinum-based drugs. Because DRC may be affected by tumor cell metabolism, we measured DRC in lymphocytes from patients with non–small-cell lung cancer (NSCLC) and compared the findings with the maximum standardized uptake value (SUVmax) on18F-fluorodeoxyglucose positron emission tomography (FDG PET) after (chemo)radiation therapy.

Autophagy not only plays an important role in the progression of cancer but is also involved in tissue inflammatory response. However, few published studies have investigated associations between functional genetic variants of autophagy-related genes and radiation pneumonitis (RP) as well as clinical outcomes in patients with NSCLC after definitive radiotherapy.

Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an impact on development, invasion, and metastasis of CM, thus likely affecting CM prognosis. Using data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center, we assessed the associations of 19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal genes with CM-specific survival and then validated significant SNPs in another genome-wide association study from Harvard University. In the single-locus analysis, 1,855 SNPs were significantly associated with CM-specific survival at P < 0.05, of which 547 SNPs were still considered noteworthy after the correction by the false-positive report probability. In the replication, two SNPs remained significantly associated with CM-specific survival after multiple comparison correction. By performing functional prediction and stepwise selection, we identified two independent SNPs (i.e., WNT2Brs1175649 G>T and BTRCrs61873997 G>A) that showed a predictive role in CM-specific survival, with an effect-allele-attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence interval = 1.41–2.81, P = 8.10 × 10−5) and 0.61 (0.46–0.80, 3.12×10−4), respectively. Collectively, these variants in the Wnt pathway genes may be biomarkers for outcomes of patients with CM, if validated by larger studies.

TiO2 is a commonly employed material for photoelectrochemical (PEC) solar water splitting due to its nontoxicity, abundance and great stability. However, TiO2 suffers from low PEC efficiency because of the weak absorption of visible light. Here, carbon quantum dots decorated C3N4/TiO2 heterostructure nanorod arrays (CQDs/C3N4/TiO2 NAs) were designed and fabricated to solve this shortcoming. The CQDs/C3N4/TiO2 NAs exhibit an increased solar to hydrogen conversion efficiency which is 5.8 times that of TiO2 NAs and excellent stability in strong alkaline electrolyte. The enhanced performance of the CQDs/C3N4/TiO2 NAs is attributed to the improved light absorption and charge separation and transfer induced by the C3N4 and CQDs. This work provides a promising approach for the design of low cost and environmentally friendly photoanodes for efficient and stable PEC applications.

The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR]=1.39; 95% confidence interval [CI]=1.16–1.66; P=.0003) and OS (adjusted HR=1.41; 95% CI=1.11-1.80; P=.005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR=0.86; 95% CI=0.56-1.33; P=.505). The present study provides evidence that the MAPK14rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.

Globally, gastric cancer is the fourth most common cancer in men and fifth most common cancer in womenHelicobacter pyloriis the most intriguing and best studied risk factor for sporadic gastric cancersSignalling pathways and cancer stem cells have key roles in carcinogenesis and progressionLocalized gastric cancer can be cured by primary surgery, but adjunctive therapies increase the cure rateNew somatic genes altered in gastric cancer (such as ARID1A, FAT4, MLLand KMT2C) have been identified, but thorough interrogation of gastric cancer is as yet incompleteTherapeutic approaches that exploit the capabilities of the host immune mechanisms hold immense promise

CASP7 plays a crucial role in cancer development and chemotherapy efficacy. We, therefore, explored whether single nucleotide polymorphisms (SNPs) of the CASP7gene can modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.

Xeroderma pigmentosum group G (XPG) protein is essential for the nucleotide excision repair system, and genetic variations in XPGERCC5that affect DNA repair capacity may contribute to the risk of tobacco-induced cancers, including squamous cell carcinoma of the head and neck (SCCHN). We investigated the association between XPGERCC5polymorphisms and risk of SCCHN.

Mouse double minute 4 (MDM4), a homolog of MDM2, is one of the key negative regulators of p53, and its amplification or overexpression contributes to carcinogenesis by inhibiting the p53 tumor suppressor activity. We investigated the association between MDM4polymorphisms and the risk of squamous cell carcinoma of the head and neck (SCCHN).

BACKGROUND Glutathione-S-transferase (GST) enzymes play a role in scavenging endogenous oxidants. Altered enzyme activity results from inherited polymorphisms, which results in increased oxidative stress. This study explores the role of GST polymorphisms as modifiers of surgical complications in patients undergoing head and neck microvascular reconstruction. METHODS Patients newly diagnosed as having head and neck cancer and undergoing microvascular reconstruction were selected. Polymerase chain reaction was used to determine GST genotypes. Demographic factors, treatment, and postoperative complications were reviewed. Multivariate logistic regression analysis was used to estimate the risk of surgical complications associated with variant genotypes. RESULTS A total of 107 patients were evaluated. Surgical and medical complication rates were 44.9% and 25.2%, respectively. The variant Val allele at the GSTP1 105 codon was associated with a significantly increased risk of surgical complications (P = .046; adjusted relative risk, 1.7; 95% confidence interval, 1.1-2.6). There was no significant association between the other GST variant genotypes and surgical complications. No association was noted between variant GST genotypes and the risk of medical complications. CONCLUSION GSTP1 codon 105 polymorphism may be a marker for risk of wound complications in head and neck microvascular reconstruction.Arch Facial Plast Surg. 2010;12(6):373-378--

p21 (WAF1/Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can induce cell cycle arrest and serve as tumor suppressors. We hypothesized that genetic variants in p21and p27may modify individual susceptibility to pancreatic cancer.

Most of the carcinogenic effects of polycyclic aromatic hydrocarbons present in tobacco smoke are mediated by the aryl hydrocarbon receptor (AHR), a ligand-dependent transcription factor that regulates tobacco-induced expression of carcinogen metabolic enzymes. We hypothesized that genetic variations in AHRmight confer individual susceptibility to lung cancer.

Polymorphisms of the methyl-CpG binding domain 1 (MBD1) gene may influence MBD1 activity on gene expression profiles, thereby modulating individual susceptibility to lung cancer. To test this hypothesis, we investigated the associations of four MBD1 polymorphisms and lung cancer risk in a Chinese population. Single locus analysis revealed significant associations between two polymorphisms (rs125555 and rs140689) and lung cancer risk (p=0.011 and p=0.005, respectively). Since the two polymorphisms were in linkage disequilibrium, further haplotype analyses were performed and revealed a significant association with lung cancer (global test p-value=0.0041). Our results suggested that MBD1 polymorphisms might be involved in the development of lung cancer. Validation of these findings in larger studies of other populations is needed.

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9–3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9–1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4–2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3–3.1; ORm1m2or [infi]m2m2: 1.3, 95% confidence interval: 1.1–1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1–4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer.