Identification of Functional Genetic Variants in Cyclooxygenase-2 and Their Association With Risk of Esophageal Cancer

Zhang, Xuemei; Miao, Xiaoping; Tan, Wen; Ning, Baitang; Liu, Zhihua; Yuan, Hong; Song, Wei; Guo, Yongli; Zhang, Xinyu; Shen, Yan; Qiang, Boqin; Kadlubar, Fred F.; Lin, Dong

doi:10.1053/j.gastro.2005.05.003

Cited by 134 publications

(244 citation statements)

References 34 publications

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“…This is in contrast to the findings of Zhang et al [12] who identified the -1195 AA genotype as a risk factor for esophageal carcinoma. It is commonly reported that COX-2 expression is higher in cancerous tissue, because high COX-2 expression contributes to and sustains inflammatory and pre-cancerous processes [4,6] .…”

Section: Discussioncontrasting

confidence: 99%

“…It is commonly reported that COX-2 expression is higher in cancerous tissue, because high COX-2 expression contributes to and sustains inflammatory and pre-cancerous processes [4,6] . Zhang et al [12] also concluded that COX-2 mRNA expression in -1195 AA genotypes was much higher than the mRNA expression in tissues of patients with the -1195 GG genotype. Our findings now suggest that the COX-2 -1195 polymorphism has the opposite effect on esophageal carcinoma risk in Caucasians, as compared to Chinese patients.…”

Section: Discussionmentioning

confidence: 98%

“…The -1195 A→G substitution in the COX-2 promotor was found to be associated with a lower expression of COX-2 in a Chinese population [12] .…”

Section: Introductionmentioning

confidence: 88%

“…The extracted DNA was used for determination of the -1195 A→G and -765 G→C polymorphisms in the COX-2 promoter by polymerase chain reaction/ restriction fragment length polymorphism (PCR/RFLP), exactly as described by Zhang et al [12] .…”

Section: Patients and Controlsmentioning

confidence: 99%

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Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Kristinsson¹,

Westerveld²,

Morsche³

et al. 2009

WJG

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AIM:To determine whether -1195 A →G and/or -765 G →C polymorphisms in Cyclooxygenase-2 (COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS:Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: T h e d i s t r i b u t i o n o f t h e -

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%

“…The -1195 A→G substitution in the COX-2 promotor was found to be associated with a lower expression of COX-2 in a Chinese population [12] .…”

Section: Introductionmentioning

confidence: 88%

Section: Patients and Controlsmentioning

confidence: 99%

See 2 more Smart Citations

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Kristinsson¹,

Westerveld²,

Morsche³

et al. 2009

WJG

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“…The following SNPs were also genotyped: PPARG2-Pro12Ala (rs1801282) (as described by Vogel et al 2007a) that has been shown to reduce transcription of target genes (Masugi et al 2000); COX2-C8473T (rs5275) (Campa et al 2004) and COX2 A-1195G (rs689466) (Vogel et al 2007b), which have been shown to up-and down-regulate the COX-2 response, respectively, among variant allele carriers (Sanak et al 2005;Zhang et al 2005).…”

Section: Selection Of Snps and Genotypingmentioning

confidence: 99%

Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil

et al. 2014

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Long-chain n-3 fatty acids (n-3 LCPUFA) improve blood pressure (BP) and lipid profile in adults and improve insulin sensitivity in rodents. We have previously shown that n-3 LCPUFA reduces BP and plasma triacylglycerol (TAG) in infants. Few studies have found effects on glucose homeostasis in humans. We explored possible effect modification by FADS, PPARG2, and COX2 genotypes to support potential effects of n-3 LCPUFA on metabolic markers in infants. Danish infants (133) were randomly allocated to daily supplementation with a teaspoon (*5 mL/day) of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age. Before and after the intervention, we assessed BP, erythrocyte n-3 LCPUFA, plasma lipid profile, insulin, and glucose in addition to functional single nucleotide polymorphisms in FADS, PPARG2, and COX2. At 18 months, plasma TAG was lower in the FO compared with SO group (p = 0.014). This effect was modified by PPARG2-Pro12Ala, as TAG only decreased among heterozygotes. FO supplemented PPARG2 Pro12Ala heterozygotes also had decreased plasma glucose compared with the SO group (p = 0.043). The effect of FO on mean arterial BP at 18 months was gender dependent (p = 0.020) and reduced in boys only (p = 0.028). Diastolic BP was, however, lower among all FO supplemented homozygous COX2-T8473C variant allele carriers compared with the SO group (p = 0.001). In conclusion, our results confirm that FO supplementation in late infancy reduces TAG and BP and indicates that the effects are mediated via peroxisome proliferator-activated receptor-c and cyclooxygenase-2. Furthermore, FO reduced plasma glucose only in PPARG2 heterozygotes.

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Effect of Concurrent Chemoradiation With Celecoxib vs Concurrent Chemoradiation Alone on Survival Among Patients With Non–Small Cell Lung Cancer With and Without Cyclooxygenase 2 Genetic Variants

Liang

Zhou

et al. 2019

JAMA Netw Open

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IMPORTANCE Treatment of locally advanced non-small cell lung cancer (NSCLC) remains challenging. The rationale of combining a cyclooxygenase 2 (COX-2) inhibitor with concurrent chemoradiation (CCRT) was based on results of preclinical research and prospective clinical studies; however, no randomized clinical trial has provided evidence of a direct comparison with CCRT alone. OBJECTIVE To determine the effect of combined selective COX-2 inhibition with standard CCRT on survival among patients with unresectable stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS A single-center, open-label, randomized phase 2 clinical trial was performed among 96 patients who had histologically and cytologically confirmed unresectable stage III NSCLC. Participants were enrolled from November 2011 to August 2015. Data were analyzed from February to October 2018. INTERVENTION Patients were randomized to receive thoracic radiation, 60 Gy, for 6 weeks concurrent with etoposide and cisplatin or the same regimen of CCRT combined with 200 mg of celecoxib, taken twice daily. MAIN OUTCOMES AND MEASURES The primary end point was overall survival. The secondary end points were the proportion of patients with treatment-related toxic effects, progression-free survival, and overall survival in subgroups with and without the COX-2 genotype. RESULTS A total of 100 patients were randomized. Following the exclusion of 4 outliers, 96 participants (96.0%) were analyzed (51 randomized to CCRT alone and 45 randomized to CCRT with celecoxib; mean [SD] age, 60.0 [8.3] years; 73.0 [76.0%] male). The median overall survival time was 32.8 (95% CI, 17.0-48.5) months in the group that received CCRT with celecoxib and 35.5 (95% CI, 25.8-45.2) months in the group that received CCRT alone (P = .88). Celecoxib with CCRT was well tolerated; the incidence of symptomatic radiation pneumonitis was 6.6% (95% CI, 1.4%-18.0%) in the group that received CCRT with celecoxib and 11.8% (95% CI, 4.4%-23.9%) in the group that received CCRT alone (P = .49). Among patients with the high-risk genotype, celecoxib plus CCRT was not associated with higher progression-free survival (hazard ratio, 0.36; 95% CI, 0.13-1.04; P = .05) or overall survival (hazard ratio, 0.50; 95% CI, 0.15-1.72; P = .26) compared with CCRT alone. CONCLUSIONS AND RELEVANCE In unresectable stage III NSCLC, adding celecoxib to concurrent chemoradiation did not improve survival. A smaller, not statistically significant proportion of patients in the CCRT with celecoxib group compared with the CCRT alone group developed symptomatic (continued) Key Points Question Could selective cyclooxygenase 2 inhibition combined with standard concurrent chemoradiation therapy improve survival among patients with unresectable stage III non-small cell lung cancer? Findings In this phase 2 clinical trial of 96 patients, adding celecoxib to concurrent chemoradiation did not improve survival. Meaning Adding celecoxib to concurrent chemoradiation did not improve survival.

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Identification of Functional Genetic Variants in Cyclooxygenase-2 and Their Association With Risk of Esophageal Cancer

Cited by 134 publications

References 34 publications

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil

Effect of Concurrent Chemoradiation With Celecoxib vs Concurrent Chemoradiation Alone on Survival Among Patients With Non–Small Cell Lung Cancer With and Without Cyclooxygenase 2 Genetic Variants

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